Expertise of a general practitioner, family medicine (GPFM). Working with primary outpatient medical records of family doctor (FDС). Information and telecommunication technologies in the medical GPFM.
Coronary heart disease (CHD) in medical practice GPSM: early detection, diagnostic criteria of different forms of ischemic heart disease , clinical protocols, routing patient organization , principles of prevention and rehabilitation. Conducting telecommunications transmission and interpretation of ECG and consult a cardiologist . The organization of clinical supervision. MPE.
Job descriptions ( JD ) general practitioner – Family doctor is a piece of legislation which establishes professional purpose , the basic terms and conditions of a general practitioner , family physician , qualifying the competence of general practitioner and family physician certification requirements for a general practitioner – Family doctor .
Job description provides ordering ( harmonization ) of requirements for a specialist – general practitioner , family doctor.
Job description is intended for management of health , ministries, departments, enterprises ( public and private institutions and organizations ) which employs a general practitioner – GP; insured customers and payers for health care , other structures related to work in primary care – health care and higher educational institutions , medical educational establishment .
General practitioner , family physician performs professional tasks, thus realizing the following competencies :
– Organization of care within defined territorial district – How to be the order of the free choice of doctor? :
– Ensuring the continuum of care that focuses on the person ( patient ) – high pressure ? Weekend ?
– Focus on community, social orientation ;
– A comprehensive approach to addressing the health needs of the patient;
– Knowledge of professional skills in solving health problems the patient;
– Holistic approach in addressing the health needs of the patient.
1. The organization of care within defined territorial district :
– Planning and implementation of the basic principles of health promotion and at the patient / the families / communities;
– Ensure patient satisfaction with initial and subsequent contacts with the health care system ;
– Forming a partnership with the patient, bringing the patient to participate in the care and treatment process ;
– Ensuring affordable health care for the attachment of the population;
– Coordination and provision of medical route patient in primary care (the function ” home “) and to higher levels of care , including health centers, rehabilitation hospitals , rehabilitation centers , institutions of social purpose , hospices , and others. , analysis of feedback ;
– Confidentiality of information in the interests of the patient;
– Organizing teamwork team territorial district ( school , school division ) primary health care to address the medical needs of the patient;
– Effective use of resources available health care system;
– Organization providing emergency medical care to patients ;
– Attract the necessary additional resources that are not prohibited by law to provide health care;
– Assess , analyze and monitor the health and quality of attachment of the population;
– Facilitate and participate in the evaluation of the epidemiological situation in the community attached to people and organizations necessary preventive and prophylactic measures ;
– Maintenance of accounting records , conducting internal monitoring work on the family territorial district , the annual report, the pre- assembly self-report for 3-5 years ;
– Ensure the principles of ethics and medical ethics in relationships with patients , their families, professional relationships with middle and junior staff of the territorial district ( institution, department of primary health care ) and nursing staff of higher levels of care ;
– Work to improve the professional level of the general practitioner , family physician and slave medical staff by undergoing regular training cycles pereatestatsiynyh , TR, intermittent courses , participation in relevant conferences and other types of training.
Coronary heart disease (CHD) in medical practice GPSM
Stable angina is chest pain or discomfort that often occurs with activity or stress. Angina is a type of chest discomfort caused by poor blood flow through the blood vessels (coronary vessels) of the heart muscle (myocardium).
Causes
The heart muscle is working all the time, so it needs a constant supply of oxygen. This oxygen is provided by the coronary arteries, which carry blood.
When the heart muscle has to work harder, it needs more oxygen. Symptoms of angina occur when the coronary arteries are narrowed or blocked by hardening of the arteries (atherosclerosis), or by a blood clot.
The most common cause of angina is coronary heart disease (CHD). Angina pectoris is the medical term for this type of chest pain.
Stable angina is less serious than unstable angina, but it can be very painful or uncomfortable.
The risk factors for coronary heart disease include:
· Diabetes
· Family history of coronary heart disease before age 50
· High LDL cholesterol and low HDL cholesterol
· Male gender
· Not getting enough exercise
· Obesity
· Smoking
Anything that makes the heart muscle need more oxygen can cause an angina attack in someone with heart disease, including:
· Cold weather
· Exercise
· Emotional stress
· Large meals
Other causes of angina include:
· Abnormal heart rhythms (usually ones that cause your heart to beat quickly)
· Anemia
· Coronary artery spasm (also called Prinzmetal’s angina)
· Heart valve disease
Angina is a specific type of pain in the chest caused by inadequate blood flow through the blood vessels (coronary vessels) of the heart muscle (myocardium).
Stable angina pectoris is a common and disabling disorder. However, the management of stable angina has not been subjected to the same scrutiny by large randomized trials as has, for example, that of acute coronary syndromes (ACS) including unstable angina and myocardial infarction (MI). The optimal strategy of investigation and treatment is difficult to define, and the development of new tools for the diagnostic and prognostic assessment of patients, along with the continually evolving evidence base for various treatment strategies, mandates that the existing guidelines be revised and updated.
Definition and pathophysiology
Stable angina is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved by rest or nitroglycerin. Less typically, discomfort may occur in the epigastric area. It is now usual to confine the term to cases in which the syndrome can be attributed to myocardial ischaemia, although essentially similar symptoms can be caused by disorders of the oesophagus, lungs, or chest wall. Although the most common cause of myocardial ischaemia is atherosclerotic CAD, demonstrable myocardial ischaemia may be induced in the abscence by hypertrophic or dilated cardiomyopathy, aortic stenosis, or other rare cardiac conditions in the absence of obstructive atheromatous coronary disease, which are not considered in this document.
Myocardial ischaemia is caused by an imbalance between myocardial oxygen supply and myocardial oxygen consumption. Myocardial oxygen supply is determined by arterial oxygen saturation and myocardial oxygen extraction, which are relatively fixed under normal circumstances, and coronary flow, which is dependent on the luminal crosssectional area of the coronary artery and coronary arteriolar tone. Both cross-sectional area and arterioloar tone may be dramatically altered by the presence of atherosclerotic plaque within the vessel wall, leading to imbalance between supply and demand when myocardial oxygen demands increase, as during exertion, related to increases in heart rate, myocardial contractility, and wall stress. Ischaemia-induced sympathetic activation can further increase the severity of ischaemia through a variety of mechanisms including a further increase of myocardial oxygen consumption and coronary vasoconstriction. The ischaemic cascade is characterized by a sequence of events, resulting in metabolic abnormalities, perfusion mismatch, regional and then global diastolic and systolic dysfunction, electrocardiographic (ECG) changes, and angina. Adenosine released by ischaemic myocardium appears to be the main mediator of angina (chest pain) through stimulation of A1 receptors located on cardiac nerve endings. Ischaemia is followed by reversible contractile dysfunction known as ‘stunning’. Recurrent episodes of ischaemia and stunning may lead to a chronic but still reversible form of dysfunction known as ‘hibernation’. A brief episode of ischaemia results in ‘preconditioning’, a powerful endogenous form of protection which makes the heart more resistant to subsequent ischaemic episodes.
Myocardial ischaemia may also be silent. Lack of pain may be due to ischaemia of insufficient duration and/or severity, to damage of afferent cardiac nerves, or to inhibition of ischaemic cardiac pain at spinal or supraspinal level. In patients who exhibit painless ischaemia, shortness of breath, and palpitation may represent anginal equivalents. Breathlessness may be due to ischaemic left ventricular (LV) systolic or diastolic dysfunction or to transient ischaemic mitral regurgitation.
In the majority of patients, the pathological substrate of stable angina is atheromatous, narrowing of the coronary arteries. The normal vascular bed has the capacity to reduce resistance such that coronary blood flow increases by up to 5–6-fold during maximal exercise. Reduction in the luminal cross-sectional area by atherosclerotic plaque reduces the normal ability of the coronary vascular bed to reduce its resistance during maximal exercise with resultant ischaemia dependent on the degree of obstruction and myocardial oxygen demands. When luminal obstruction is ≤40% maximal flow during exercise can usually be maintained. But luminal diameter reduction of> 50% may be associated with ischaemia when coronary blood flow becomes inadequate to meet cardiac metabolic demand during exercise or stress. Stenosis resistance changes relatively little with mild degrees of vascular narrowing but rises precipitously with severe obstruction, with resistance almost tripling between stenosis of 80% and 90%. For a similar degree of stenosis, the ischaemic threshold is influenced by other factors including the degree of development of collateral circulation, the degree of transmural distribution of myocardial perfusion from the more vulnerable subendocardium to the subepicardium, coronary vascular tone, and platelet aggregation. Endothelial dysfunction as a cause of angina is discussed in Syndrome X. Rarely, angina may be caused by myocardial bridging.
In stable angina, the angina threshold may vary considerably from day to day and even during the same day. Symptom variability is due to a variable degree of vasoconstriction at the site of critical stenoses (dynamic stenoses) and/or distal coronary vessels, depending on factors such as ambient temperature, mental stress, and neuro-hormonal influences. In a sizeable proportion of patients, angina may occasionally occur even at rest.
Patients with stable angina are at risk of developing an ACS: unstable angina, non-ST-elevation MI or ST-elevation MI. Unstable angina is characterized by a sudden worsening of angina symptoms, which become more frequent, more prolonged, and more severe and/or occur at a lower threshold or at rest. MI is characterized by prolonged angina (>30 min) associated with myocardial necrosis. Both non-ST-elevation and ST-elevation MI are frequently preceded by a period of days, or even weeks, of unstable symptoms. The common pathological background of ACS is erosion, fissure, or rupture of an atherosclerotic coronary plaque associated with platelet aggregation, leading to subtotal or total thrombotic coronary occlusion. Activated platelets release a number of vasoconstrictors, which may further impair coronary flow through the stimulation of vascular smooth muscle cells both locally and distally. The haemodynamic severity of the atherosclerotic plaque prior to destabilization is frequently mild and the plaques are lipid filled with foam cells. Intravascular ultrasound studies have shown that so-called vulnerable plaques (i.e. at risk of cap rupture) that are <50% in diameter both precede and predict future acute syndromes occurring precisely in their neighbourhood. Activation of inflammatory cells within the atherosclerotic plaque appears to play an important role in the destabilization process, leading to plaque erosion, fissure, or rupture. More recently, the concept of a single vulnerable plaque causing an ACS has been challenged in favour of a more generalized inflammatory response.
Symptoms and signs
Symptoms of stable angina are often predictable. This means that the same amount of exercise or activity may cause your angina to occur. Your angina should improve or go away when you stop or slow down the exercise.
The most common symptom is chest pain that occurs behind the breastbone or slightly to the left of it. The pain of stable angina usually begins slowly and gets worse over the next few minutes before going away.
The pain may feel like tightness, heavy pressure, squeezing, or crushing pain. It may spread to the:
· Arm (usually the left)
· Back
· Jaw
· Neck
· Shoulder
Some people say the pain feels like gas or indigestion.
Some patients (women, older adults, and people with diabetes) may have different symptoms, such as:
· Back, arm, or neck pain
· Fatigue
· Shortness of breath
· Weakness
The pain of stable angina usually:
· Occurs after activity or stress
· Lasts an average of 1 – 15 minutes
· Is relieved with rest or a medicine called nitroglycerin
Angina attacks can occur at any time during the day, but a higher number occur between 6 a.m. and noon.
Other symptoms of angina include:
· A feeling of indigestion or heartburn
· Dizziness or light-headedness
· Nausea, vomiting, and sweating
· Shortness of breath
· Unexplained tiredness after activity (more common in women)
A careful history remains the cornerstone of the diagnosis of angina pectoris. In the majority of cases, it is possible to make a confident diagnosis on the basis of the history alone, although physical examination and objective tests are necessary to confirm the diagnosis and assess the severity of underlying disease.
The characteristics of discomfort related to myocardial ischaemia (angina pectoris) have been extensively described and may be divided into four categories, location, character, duration, and relation to exertion and other exacerbating or relieving factors. The discomfort caused by myocardial ischaemia is usually located in the chest, near the sternum, but may be felt anywhere from the epigastrium to the lower jaw or teeth, between the shoulder blades or in either arm to the wrist and fingers. The discomfort is usually described as pressure, tightness, or heaviness, sometimes strangling, constricting, or burning. The severity of the discomfort varies greatly and is not related to the severity of the underlying coronary disease. Shortness of breath may accompany angina, and chest discomfort may be also be accompanied by less specific symptoms such as fatigue or faintness, nausea, burping, restlessness, or a sense of impending doom.
The duration of the discomfort is brief, nomore than 10 min in the majority of cases, and more commonly even minutes less. An important characteristic is the relation to exercise, specific activities, or emotional stress. Symptoms classically deteriorate with increased levels of exertion, such as walking up an incline, or against a breeze and rapidly disappear within a few minutes, when these causal factors abate. Exacerbations of symptoms after a heavy meal or first thing in the morning are classical features of angina. Buccal or sublingual nitrates rapidly relieve angina, and a similar rapid response may be observed with chewing nifedipine capsules.
Non-anginal pain lacks the characteristic qualities described, may involve only a small portion of the left hemithorax, and last for several hours or even days. It is usually not relieved by nitroglycerin (although it may be in the case of oesophageal spasm) and may be provoked by palpation. Noncardiac causes of pain should be evaluated in such cases. Definitions of typical and atypical angina have been previously published, summarized on Table 2.
It is important when taking the history to identify those patients with unstable angina, which may be associated with plaque rupture, who are at significantly higher risk of an acute coronary event in the short-term. Unstable angina may present in one of the three ways: (i) as rest angina, i.e. pain of characteristic nature and location, but occurring at rest and for prolonged periods, up to 20 min; (ii) rapidly increasing or crescendo angina, i.e. previously stable angina, which progressively increases in severity and intensity and at lower threshold over a short period, 4 weeks or less; or (iii) new onset angina, i.e. recent onset of severe angina, such that the patient experiences marked limitation of ordinary activity within 2 months of initial presentation. The investigation and management of suspected unstable angina is dealt with in guidelines for the management of ACS.
For patients with stable angina, it is also useful to classify the severity of symptoms using a grading system such as that of the Canadian Cardiovascular Society Classification (Table 3). This is useful in determining the functional impairment of the patient and quantifying response to therapy. The Canadian Cardiovascular Society Classification is widely used as a grading system for angina to quantify the threshold at which symptoms occur in relation to physical activities. Alternative classification systems such as Duke Specific Activity Index and Seattle angina questionnaire may also be used in determining the functional impairment of the patient and quantifying response to therapy and may offer superior prognostic capability.
Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension, valvular heart disease, or hypertrophic obstructive cardiomyopathy. Physical examination should include assessment of body-mass index (BMI) and waist circumference to assist evaluation of the metabolic syndrome, evidence of non-coronary vascular disease which may be asymptomatic, and other signs of comorbid conditions. However, there are no specific signs in angina pectoris. During or immediately after an episode of myocardial ischaemia, a third or fourth heart sound may be heard and mitral insufficiency may also be apparent during ischaemia. Such signs are, however, elusive and non-specific.
Laboratory tests
Laboratory investigations may be loosely grouped into those that provide information related to possible causes of ischaemia, those that may be used to establish cardiovascular risk factors and associated conditions, and those that may be used to determine prognosis. Some laboratory investigations are used for more than one of these purposes and may be applied routinely in all patients, whereas other investigations should be reserved for use where clinical history and/or examination indicates a particular need for their application.
Haemoglobin and, where there is clinical suspicion of a thyroid disorder, thyroid hormones provide information related to possible causes of ischaemia. The full blood count incorporating total white cell count as well as haemoglobin may also add prognostic information. If there is clinical suspicion of instability, biochemical markers of myocardial damage such as troponin or CKMB (creatine kinase myocardial band), measured by mass assay, should be employed to exclude myocardial injury. If these markers are elevated, management should continue as for an ACS rather than stable angina. After initial assessment, these tests are not recommended as routine investigations during each subsequent evaluation. Fasting plasma glucose and fasting lipid profile including total cholesterol (TC), high density lipoprotein (HDL) cholesterol, and low density lipoprotein (LDL) cholesterol, and triglycerides should be evaluated in all patients with suspected ischaemic disease, including stable angina, to establish the patient’s risk profile and ascertain the need for treatment. Lipid profile and glycaemic status should be re-assessed periodically to determine efficacy of treatment and ion-diabetic patients to detect new development of diabetes. There is no evidence to support recommendations for how regularly reassessment should take place. Consensus suggests annual measurement. Patients with very high levels of lipids, in whom the progress of any interventioeeds to be monitored, should have measurements more frequently. Patients with diabetes should be managed accordingly.
Serum creatinine is a simple but crude method to evaluate renal function. Renal dysfunction may occur due to associated comorbidity such as hypertension, diabetes or renovascular disease and has a negative impact on prognosis in patients with CVD, giving good grounds for measurement at initial evaluation in all patients with suspected angina. The Cockcroft–Gault formula may be used to estimate creatinine clearance based on age, sex, weight, and serum creatinine. The commonly used formula is as follows: ((140—age (years)) [1] (actual weight (kg)))/(72 * serum creatinine (mg/dL)), with multiplication by a factor of 0.85 if female.
In addition to the well-recognized association between adverse cardiovascular outcome and diabetes, elevations of fasting or post-glucose challenge glycaemia have also been shown to predict adverse outcome in stable coronary disease independently of conventional risk factors. Although HbAIc predicts outcome in the general population, there is less data in those with CAD. Obesity, and in particular evidence of the metabolic syndrome, is predictive of adverse cardiovascular outcome in patients with established disease as well as asymptomatic populations. The presence of the metabolic syndrome can be determined from assessment of waist circumference (or BMI), blood pressure, HDL, triglycerides, and fasting glucose levels and offers additional prognostic information to that obtained from conventional Framingham risk scores without major additional cost in terms of laboratory investigation.
Further laboratory testing, including cholesterol subfractions (ApoA and ApoB) homocysteine, lipoprotein (a) (Lpa), haemostatic abnormalities, and markers of inflammation such as hs-C-reactive protein, have been the subject of much interest as methods to improve current risk prediction. However, markers of inflammation fluctuate over time and may not be a reliable estimator of risk in the longer term. More recently, NT-BNP has been shown to be an important predictor of long-term mortality independent of age, ventricular ejection fraction (EF), and conventional risk factors. As yet, there is inadequate information regarding how modification of these biochemical indices can significantly improve on current treatment strategies to recommend their use in all patients, particularly given the constraints of cost and availability. Nevertheless, these measurements have a role in selected patients, for example, testing for haemostatic abnormalities in those with prior MI without conventional risk factors, or a strong family history of coronary disease, or where resources are not limited. Further research into their use is welcomed. The use of glycated haemoglobin or response to oral glucose load in addition to a single measurement of fasting plasma glucose have also been shown to improve detection of glycaemic abnormalities, but as yet there is insufficient evidence to recommend this strategy in all patients with chest pain. This may be a useful method of detecting glycaemic abnormalities in selected patients particularly at high risk for their development.
Recommendations for laboratory investigation in initial
assessment of stable angina
Class I (in all patients)
(1) Fasting lipid profile, including TC, LDL, HDL, and triglycerides (level of evidence B)
(2) Fasting glucose (level of evidence B)
(3) Full blood count including Hb and white cell count (level of evidence B)
(4) Creatinine (level of evidence C)
Class I (if specifically indicated on the basis of clinical evaluation)
(1) Markers of myocardial damage if evaluation suggests clinical instability or ACS (level of evidence A)
(2) Thyroid function if clinically indicated (level of evidence C)
Class IIa
(1) Oral glucose tolerance test (level of evidence B)
Class IIb
(1) Hs-C-reactive protein (level of evidence B)
(2) Lipoprotein a, ApoA, and ApoB (level of evidence B)
(3) Homocysteine (level of evidence B)
(4) HbA1c (level of evidence B)
(5) NT-BNP (level of evidence B)
Recommendations for blood tests for routine
reassessment in patients with chronic stable angina
Class IIa
(1) Fasting lipid profile and fasting glucose on an annual basis (level of evidence C)
Chest X-ray
A chest X-ray (CXR) is frequently used in the assessment of patients with suspected heart disease. However, in stable angina, the CXR does not provide specific information for diagnosis or risk stratification. The test should be requested only in patients with suspected heart valvular disease, or pulmonary disease.The presence of cardiomegaly, pulmonary congestion, atrial enlargement, and cardiac calcifications has been related to impaired prognosis.
Recommendations for CXR for initial diagnostic
assessment of angina
Class I
(1) CXR in patients with suspected heart failure (level of evidence C)
(2) CXR in patients with clinical evidence of significant pulmonary disease (level of evidence B)
Non-invasive cardiac investigations
This section will describe investigations used in the assessment of angina and concentrate on recommendations for their use in diagnosis and evaluation of efficacy of treatment, and recommendations for risk stratification will be dealt with in the following section. As there are few randomized trials assessing health outcomes for diagnostic tests, the available evidence has been ranked according to evidence from non-randomized studies or meta-analyses of these studies.
Resting ECG
All patients with suspected angina pectoris based on symptoms should have a resting 12-lead ECG recorded. It should be emphasized that a normal resting ECG is not uncommon even in patients with severe angina and does not exclude the diagnosis of ischaemia. However, the resting ECG may show signs of CAD such as previous MI or an abnormal repolarization pattern. The ECG may assist in clarifying the differential diagnosis if taken in the presence of pain, allowing detection of dynamic ST-segment changes in the presence of ischaemia, or by identifying features of pericardial disease. An ECG during pain may be particularly useful if vasospasm is suspected. The ECG may also show other abnormalities such as left ventricular hypertrophy (LVH), left bundle branch block (LBBB), pre-excitation, arrhythmias, or conduction defects. Such information may be helpful in defining the mechanisms responsible for chest pain, in selecting appropriate further investigation, or in tailoring individual patient treatment. The resting ECG also has an important role in risk stratification, as outlined in the Risk Stratification section.
There is little direct evidence to support routinely repeating the resting ECG at frequent intervals unless to obtain an ECG during pain or if there has been a change in functional class.
Recommendations for resting ECG for initial diagnostic
assessment of angina
Class I (in all patients)
(1) Resting ECG while pain free (level of evidence C)
(2) Resting ECG during episode of pain (if possible) (level of evidence B)
Recommendations for resting ECG for routine reassessment in patients with chronic stable angina
Class IIb
(1) Routine periodic ECG in the absence of clinical change (level of evidence C)
ECG stress testing
A further factor that may influence the performance of the exercise ECG as a diagnostic tool is the definition of a positive test. ECG changes associated with myocardial schaemia include horizontal or down-sloping ST-segment depression or elevation [≥1 mm (0.1 mV) for ≥60–80 ms after the end of the QRS complex], especially when these changes are accompanied by chest pain suggestive of angina, occur at a low workload during the early stages of exercise and persist for more than 3 min after exercise. ncreasing the threshold for a positive test, for example, to ≥2 mm (0.2 mV) ST-depression, will increase specificity at the expense of sensitivity. A fall in systolic pressure or ack of increase of blood pressure during exercise and the appearance of a systolic murmur of mitral regurgitation or ventricular arrhythmias during exercise reflect impaired LV function and increase the probability of severe myocardial schaemia and severe CAD. In assessing the significance of the test, not only the ECG changes but also the workload, heart rate increase and blood pressure response, heart rate recovery after exercise, and the clinical context should be considered. It has been suggested that evaluatng ST changes in relation to heart rate improves reliability of diagnosis but this may not be so in symptomatic populations.
An exercise test should be carried out only after careful clinical evaluation of symptoms and a physical examination ncluding resting ECG. Complications during exercise testing are few but severe arrhythmias and even sudden death can occur. Death and MI occur at a rate of less than or equal to one per 2500 tests. Accordingly, exercise testing should only be performed under careful monitoringthe appropriate setting. A physician should be present or immediately available to monitor the test. The ECG should be continuously recorded with a printout at preselected intervals, mostly at each minute during exercise, and 2–10 min of recovery after exercise. Exercise ECG should not be carried out routinely in patients with known severe aortic stenosis or hypertrophic cardiomyopathy, although carefully supervised exercise testing may be used to assess functional capacity in selected individuals with these conditions.
Either the Bruce protocol or one of its modifications on a treadmill or a bicycle ergometer can be employed. Most consist of several stages of exercise, increasing in intensity, either speed, slope, or resistance or a combination of these factors, at fixed intervals, to test functional capacity. It is convenient to express oxygen uptake in multiples of resting requirements. One metabolic equivalent (MET) is a unit of sitting/resting oxygen uptake [3.5 mL of O2 per kilogram of body weight per minute (mL/kg/min)]. Bicycle workload is frequently described in terms of watts (W). ncrements are of 20 W per 1 min stage starting from 20 to 50 W, but increments may be reduced to 10 W per stage in patients with heart failure or severe angina. Correlation between METs achieved and workload in watts varies with numerous patient-specific and environmental factors.
The reason for stopping the test and the symptoms at that time, including their severity, should be recorded. Time to the onset of ECG changes and/or symptoms, the overall exercise time, the blood pressure and heart rate response, the extent and severity of ECG changes, and the postexercise recovery rate of ECG changes and heart rate should also be assessed. For repeated exercise tests, the use of the Borg scale or similar method of quantifying symptoms may be used to allow comparisons.
Recommendations for exercise ECG for initial
diagnostic assessment of angina
Class I
(1) Patients with symptoms of angina and intermediate pre-test probability of coronary disease based on age, gender, and symptoms, unless unable to exercise or displays ECG changes which make ECG non-evaluable (level of evidence B)
Class IIb
(1) Patients with
1 mm ST-depression on resting ECG or taking digoxin (level of evidence B)
(2) In patients with low pre-test probability (,10% probability) of coronary disease based on age, gender, and symptoms (level of evidence B)
Recommendations for exercise ECG for routine
re-assessment in patients with chronic stable angina
Class IIb
(1) Routine periodic exercise ECG in the absence of clinical change (level of evidence C)
Tissue Doppler imaging allows regional quantification of myocardial motion (velocity), and strain and strain rate imaging allow determination of regional deformation, strain being the difference in velocity between adjacent regions and strain rate being the difference per unit length. Tissue Doppler imaging and strain rate imaging have improved the diagnostic performance of tress echocardiography improving the capability of echocardiography to detect ischaemia earlier in the ischaemic cascade. Because of the quantitative nature of the techniques, inter-operator variability and subjectivity in interpretation of the results are also reduced. Hence, tissue Doppler and strain rate imaging are expected to complement current echocardiographic techniques for ischaemia detection and improve the accuracy and reproducibility of stress echocardiography in the broader clinical setting. There is also some evidence that tissue Doppler imaging may improve the prognostic utility of stress echocardiography.
Recommendations for the use of exercise stress with imaging techniques (either echocardiography or perfusion) in the initial diagnostic assessment of angina
Class I
(1) Patients with resting ECG abnormalities, LBBB, .1mm ST-depression, paced rhythm, or WPW which prevent accurate interpretation of ECG changes during stress (level of evidence B)
(2) Patients with a non-conclusive exercise ECG but reasonable exercise tolerance, who do not have a high probability of significant coronary disease and in whom the diagnosis is still in doubt (level of evidence B)
Class IIa
(1) Patients with prior revascularization (PCI or CABG) in whom localization of ischaemia is important (level of evidence B)
(2) As an alternative to exercise ECG in patients where facilities, cost, and personnel resources allow (level of evidence B)
(3) As an alternative to exercise ECG in patients with a low pre-test probability of disease such as women with atypical chest pain (level of evidence B)
(4) To assess functional severity of intermediate lesions on coronary arteriography (level of evidence C)
(5) To localize ischaemia when planning revascularization options in patients who have already had arteriography (level of evidence B)
Recommendations for the use of pharmacological stress with imaging techniques (either echocardiography or perfusion) in the initial diagnostic assessment of angina
Class I, IIa, and IIb indications as above if the patient is unable to exercise adequately.
Stress cardiac magnetic resonance. CMR stress testing in conjunction with a dobutamine infusion can be used to detect wall motion abnormalities induced by ischaemia. The technique has been shown to compare favourably to dobutamine stress echocardiography (DSE) because of higher quality imaging. Thus, dobutamine stress CMR has been shown to be very effective in the diagnosis of CAD in patients who are unsuitable for dobutamine echocardiography. Studies of outcome following dobutamine CMR show a low event rate when dobutamine CMR is normal.
Myocardial perfusion CMR now achieves comprehensive ventricular coverage using multislice imaging. Analysis is either visual to identify low signal areas of reduced perfusion, or with computer assistance with quantification of the upslope of myocardial signal increase during the first pass. Although CMR perfusion is still in development for clinical application, the results are already very good in comparison with X-ray coronary angiography, PET, and SPECT.
A recent consensus panel reviewing the current indications for CMR thus gave class II recommendations for CMR wall motion and CMR perfusion imaging (Class II provides clinically relevant information and is frequently useful; other techniques may provide similar information; supported by limited literature).
Echocardiography at rest
Resting two-dimensional and doppler echocardiography is useful to detect or rule out the possibility of other disorders such as valvular heart disease or hypertrophic cardiomyopathy as a cause of symptoms, and to evaluate ventricular function. For purely diagnostic purposes, echo is useful in patients with clinically detected murmurs, history and ECG changes compatible with hypertrophic cardiomyopathy or previous MI, and symptoms or signs of heart failure. Cardiac magnetic resonance may be also be used to define structural cardiac abnormalities and evaluate ventricular function, but routine use for such purposes is limited by availability.
The true prevalence of isolated diastolic heart failure is difficult to quantify because of heterogeneity in definitions and variability in populations studied. Community-based studies have an independent association between diastolic heart failure and a history of ischaemic heart disease, including angina, strengthening the case for echocardiography in all patients with angina, and signs or symptoms of heart failure. Universal resting echocardiography in a stable angina population without heart failure may also identify previously undetected diastolic dysfunction. Recent developments in tissue Doppler imaging and strain rate measurement have greatly improved the ability to study diastolic function but the clinical implications of isolated diastolic dysfunction in terms of treatment or prognosis are less well defined. Diastolic function may improve with anti-ischaemic therapy. However, treatment of diastolic dysfunction as a primary aim of therapy in stable angina is not yet warranted. There is no indication for repeated use of resting echocardiography on a regular basis in patients with uncomplicated stable angina in the absence of a change in clinical condition.
Although the diagnostic yield of evaluation of cardiac structure and function in patients with angina is mostly concentrated in specific subgroups, estimation of ventricular function is extremely important in risk stratification, where echocardiography (or alternative methods of assessment of ventricular function) has much wider indications.
Recommendations for echocardiography for initial diagnostic assessment of angina
Class I
(1) Patients with abnormal auscultation suggesting valvular heart disease or hypertrophic cardiomyopathy(level of evidence B)
(2) Patients with suspected heart failure (level ofevidence B)
(3) Patients with prior MI (level of evidence B)
(4) Patients with LBBB, Q-waves, or other significant pathological changes on ECG, including ECG LVH (level of evidence C)
Ambulatory ECG monitoring
Ambulatory ECG (Holter) monitoring may reveal evidence of myocardial ischaemia during normal ‘daily’ activities, but rarely adds important diagnostic information in chronic stable angina pectoris over and above that provided by an exercise test. Ambulatory silent ischaemia has been reported to predict adverse coronary events and there is conflicting evidence that the suppression of silent ischaemia in stable angina improves cardiac outcome. The significance of silent ischaemia in this context is different from that in unstable angina where it has been shown that recurrent silent ischaemia predicts an adverse outcome. Prognostic studies in stable angina seem to identify silent ischaemia on ambulatory monitoring as a harbinger of hard clinical events (fatal and non-fatal MI) only in highly selected patients with ischaemia detectible on exercise testing, and there is little evidence to support its routine deployment as a prognostic implement in this clinical setting.
Ambulatory monitoring may have a role, however, in patients in whom vasospastic angina is suspected. Finally, in patients with stable angina and suspected major arrhythmias, Holter monitoring is an important method of diagnosing arrhythmias. Repeated ambulatory ECG monitoring as means to evaluate patients with chronic stable angina is not recommended.
Recommendations for ambulatory ECG for initial diagnostic assessment of angina
Class I
(1) Angina with suspected arrhythmia (level of evidence B) Class IIa
(1) Suspected vasospastic angina (level of evidence C)
Non-invasive techniques to assess coronary calcification and coronary anatomy
Computed tomography. Although spatial resolution and movement artefact have for a long time been limiting factors in computed tomography (CT) cardiac imaging, considerable advances in technology have been made in recent years to overcome these issues. Two modalities of CT imaging have developed to improve spatial and temporal resolution in CT, ultra-fast or electron beam CT (EBCT), and multi-detector or multi-slice CT (MDCT). These have been accompanied by improvements in processing software to facilitate interpretation of the images acquired. Both techniques have been validated as effective in the detection of coronary calcium and quantification of the extent of coronary calcification. The Agatston score, the most commonly used score, is based on the area and density of calcified plaques. It is computed by specific software and is used to quantify the extent of coronary calcification.
Calcium is deposited in atherosclerotic plaques within the coronary arteries. Coronary calcification increases with age, and nomograms have been developed to facilitate interpretation of calcium scores relative to the expected values for a given age and gender. The extent of coronary calcification correlates more closely with the overall burden of plaque than with the location or severity of stenoses. Thus in population-based studies detection of coronary calcium may identify those at higher risk of significant coronary disease, but assessment of coronary calcification is not recommended routinely for the diagnostic evaluation of patients with stable angina.
Image acquisition times and resolution for EBCT and MDCT have been shortened to the extent that CT coronary arteriography can be performed by injection of intravenous contrast agents. MDCT or multi-slice CT appears to be the most promising of the two techniques in terms of non-invasive imaging of the coronary arteries, with preliminary studies suggesting excellent definition, and the possibility of examining arterial wall and plaque characteristics. Sensitivity and specificity (segment-specific) of CT angiography for the detection of coronary disease has been reported to be 95 and 98%, respectively, using 16-slice CT scanners. Studies using 64 detector scanning report sensitivities and specificities of 90–94% and 95–97%, respectively, and importantly, a negative predictive value of 93–99%. Non-invasive CT arteriography holds considerable promise for the future of the diagnostic assessment of coronary disease. Optimal use of this rapidly developing technology will harness the skills of both radiology and cardiology disciplines, with cardiology necessarily taking the lead in selection of patients for investigation by this method, and appropriate management based on the results. At present, although the diagnostic accuracy of this technique has been reported, the prognostic utility, and the exact place in the hierarchy of investigations in stable angina has not yet been fully defined. A conservative suggestion for its use would be in patients with a low pre-test (<10%) probability of disease with an equivocal functional test (exercise ECG or stress imaging).
Recommendations for the use of CT angiography in stable angina
Class IIb
(1) Patients with a low pre-test probability of disease, with a non-conclusive exercise ECG or stress imaging test (level of evidence C)
Magnetic resonance arteriography. Similar to the case of CT, advances in magnetic resonance technology permit noninvasive MR contrast coronary arteriography, and hold the potential for plaque characterization. Advantages of the technique include the considerable potential for evaluation of overall cardiac anatomy and function. However, at present this can only be regarded as a valuable tool for research and is not recommended as routine clinical practice in the diagnostic evaluation of stable angina.
Invasive techniques to assess coronary anatomy
Coronary arteriography
Coronary arteriography is generally undertaken as part of a series of tests to establish a diagnosis and ascertain treatment options. Non-invasive testing can establish the likelihood of the presence of obstructive coronary disease with an acceptable degree of certainty, and through appropriate risk stratification may be used to determine the need for coronary arteriography for further risk stratification purposes. However, it may be contraindicated for reasons of disability or serious comorbidity, or offer inconclusive results. After a resuscitated cardiac arrest or life threatening ventricular arrhythmia, a definitive diagnosis regarding the presence or absence of coronary disease is useful in clinical decision-making. In addition, non-invasive testing does not allow assessment of suitability for revascularization which may be considered for symptomatic as well as prognostic grounds. Coronary arteriography holds a fundamental position in the investigation of patients with stable angina, providing reliable anatomical information to identify the presence or absence of coronary lumen stenosis, define therapeutic options (suitability of medical treatment or myocardial revascularization), and determine prognosis. Methods used to perform coronary arteriography have improved substantially resulting in the reduction of complication rates and rapid ambulation. The composite rate of major complications associated with routine diagnostic catheterization in patients is between 1 and 2%. The composite rate of death, MI, or stroke is of the order of 0.1–0.2%.
Intravascular ultrasound
Intravascular ultrasound is a technique that allows production of ultrasound images from within the (coronary) arteries by passing an ultrasound catheter into the coronary artery lumen. Intravascular ultrasound allows for accurate measurement of coronary luminal diameter, assessment of eccentric lesions and Glagovian remodelling, and quantification of atheroma and calcium deposition. It also allows for detailed assessment of interventional target lesions, stent placement, apposition and expansion, and transplant vasculopathy. The technique has afforded advantages in terms of our understanding of atherosclerotic plaque deposition and progression, offering considerably improved qualitative and quantitative assessment of coronary anatomy compared with contrast arteriography and doubtless, has an important role in specialized clinical settings, particularly as an adjunct to coronary intervention. However, it is more appropriately used in highly specific clinical settings and for research purposes than widespread application as a first line investigation for coronary disease.
Recommendations for coronary arteriography for the purposes of establishing a diagnosis in stable angina
Class I
(1) Severe stable angina (Class 3 or greater of Canadian Cardiovascular Society Classification), with a high pre-test probability of disease, particularly if the symptoms are inadequately responding to medical treatment (level of evidence B)
(2) Survivors of cardiac arrest (level of evidence B)
(3) Patients with serious ventricular arrhythmias (level of evidence C)
(4) Patients previously treated by myocardial revascularization (PCI, CABG) who develop early recurrence of moderate or severe angina pectoris (level of evidence C)
Class IIa
(1) Patients with an inconclusive diagnosis oon-invasive testing, or conflicting results from different noninvasive modalities at intermediate to high risk of coronary disease (level of evidence C)
(2) Patients with a high risk of restenosis after PCI if PCI has been performed in a prognostically important site (level of evidence C)
Risk stratification
The long-term prognosis of stable angina is variable, and the range of treatment options has expanded considerably from simple symptomatic control to potent and often expensive strategies to improve prognosis. When discussing risk stratification in stable angina, risk refers primarily to the risk of cardiovascular death, but the term is often more loosely applied to incorporate cardiovascular death and MI, or in some cases even wider combinations of cardiovascular endpoints. The process of risk stratification serves a dual purpose, to facilitate an informed response to queries regarding prognosis from patients themselves, employers, insurers, non-cardiology specialists considering treatment options for comorbid conditions and others, and secondly to assist in choosing appropriate treatment.
For certain management options, particularly revascularization and/or intensified pharmacological therapy, prognostic benefit is only apparent in high-risk subgroups, with limited if any benefit in those whose prognosis is already good. This mandates identification of those patients at highest risk, and therefore most likely to benefit from more aggressive treatment, early in the assessment of stable angina.
A 10-year cardiovascular mortality of >5% (>0.5% per annum) is determined to be high risk for the purpose of implementing primary prevention guidelines. However, absolute levels of what constitutes high-risk and low-risk are not clearly defined for those with established CVD.This problem is linked to difficulties in comparing risk prediction systems across different populations, determining accuracy of individualized predictions of risk, and synthesis of multiple components of risk, often studied separately, into an estimate of risk for an individual. Added to continuously evolving public and professional perceptions of what constitutes high- and low-risk over the past four to five decades (since many of the initial risk predictors were defined), the reasons for this lack of definition are not easily overcome.
However, while awaiting development of a robust and portable risk prediction model which incorporates all potential aspects of risk stratification, there is an alternative pragmatic approach, based on clinical trial data. The inherent problems with bias when interpreting and generalizing clinical trial data must be recognized, but such data offer an estimate of the levels of absolute risk achievable with modern conventional treatment even in patients with proven vascular disease. This in turn facilitates an estimation of what may be accepted as constituting high, low, and intermediate risk in a contemporary setting for the purposes of determining the threshold for invasive investigation or intensified pharmacological therapy.
The cardiovascular mortality and MI rate observed in the placebo arms of large trials of secondary prevention or anti-anginal therapy in stable coronary disease published since 2000 are illustrated in Figure 1. The rate of cardiovascular death in the PEACE study was less than 1% per annum, whereas in ‘high-risk’ populations such as in diabetic MICRO-HOPE population and the IONA population the annualized cardiovascular mortality rate was >2%. For the purposes of these guidelines, unless qualified differently in the text, if an individual with angina is determined on the basis of a well validated risk prediction model, to have annual cardiovascular mortality of >2% that individual is deemed high risk, whereas an annual cardiovascular mortality of <1% is considered low risk, and 1–2% intermediate risk.
The clinical evaluation, the response to stress testing, the quantification of ventricular function, and the extent of CAD are the four key pieces of information to stratify patient’s risk. However, not all patients will require invasive assessment of the coronary anatomy, particularly if their clinical evaluation and non-invasive testing establish that they are in a low-risk group. The risk assessment hierarchy can be described as:
(1) Risk stratification by clinical evaluation
(2) Risk stratification by response to stress testing
(3) Risk stratification by ventricular function
(4) Risk stratification by coronary anatomy
The route through these successive tests may not always be directly linear. For example in a patient with a high pre-test probability of disease, severe angina, and other high-risk clinical features such as signs of heart failure, may proceed directly from clinical evaluation to coronary arteriography, with perfusion scintigraphy afterwards to evaluate myocardial viability. However, risk stratification generally follows a pyramidal structure, with all patients requiring risk stratification by clinical evaluation as the most basic requirement, proceeding in the majority to noninvasive assessment of ischaemia and ventricular function, and finally coronary arteriography in a selected proportion.
Risk stratification using clinical evaluation
The clinical history and physical examination can provide very important prognostic information. ECG can be conveniently incorporated in risk stratification at this level, and the results of the laboratory tests discussed in the previous section may modify risk estimation further. Diabetes, hypertension, current smoking, and elevated total cholesterol (untreated or elevated despite treatment) have been shown to be predictive of adverse outcome in patients with stable angina or other populations with established coronary disease.
Increasing age is an important factor to consider, as are prior MI, symptoms and signs of heart failure, and the pattern of occurrence (recent onset or progressive), and severity of angina, particularly if unresponsive to therapy.
Pryor et al. studied a total of 1030 consecutive outpatients referred to non-invasive testing for suspected CAD; the information from the initial history, physical examination, ECG, and chest radiograph was used to predict coronary anatomy, i.e. the likelihood of any significant coronary disease, severe disease, and significant left main (LM) disease and to estimate 3 years survival. These estimates were compared with those based on treadmill testing. Compared with the treadmill exercise test, initial evaluation was slightly better able to distinguish patients with or without CAD and was similar in the ability to identify patients at increased risk for dying or with anatomically severe disease. Although much of the information obtained by physicians during the initial assessment is subjective, their study confirms the importance of that information in identifying patients likely to benefit from further testing and supports the development of strategies that use the physician’s initial assessment in the evaluation process.
Typical angina has been shown to be a significant prognostic factor in patients undergoing coronary arteriography, however, the relation of typical angina to prognosis is mediated by its relation to the extent of coronary disease. But the pattern of angina occurrence, angina frequency, and resting ECG abnormalities are independent predictors of survival and survival free of MI, and may be combined in a simple weighted score (Figure 3) to predict outcome, particularly in the first year after assessment.
The effect of angina score on prognosis is not apparent after 3 years and is greatest when ventricular function is maintained. This is due to the profound effect of impaired ventricular function on prognosis, which when present, greatly outweighs the effect of symptom severity. The association between the pattern of angina occurrence, particularly the development of new onset symptoms, with adverse prognosis may be due to overlap with the milder end of the spectrum of unstable angina. Furthermore, with more severe angina, the likelihood of coronary revascularization for prognostically important disease increases, which may also contribute to the time-dependency of symptom severity in predicting risk.
Physical examination may also help in determining risk. The presence of peripheral vascular disease (either lower limb or carotid) identifies patients at increased risk of subsequent cardiovascular events in stable angina. In addition, signs related to heart failure (which reflect LV function) convey an adverse prognosis.
Patients with stable angina who have resting ECG abnormalities: evidence of prior MI, LBBB, left anterior hemiblock, LVH, second or third degree AV block, or AF are at greater risk of future cardiovascular events than those with a normal ECG. It is possible that in an unselected population with stable angina the baseline risk is lower than in many of the studies quoted accepting that many of these studies have been conducted in patients referred for further angiographic evaluation.
Recommendations for risk stratification by clinical evaluation, including ECG and laboratory tests in stable angina
Class I
(1) Detailed clinical history and physical examination including BMI and/or waist circumference in all patients, also including a full description of symptoms, quantification of functional impairment, past medical history, and cardiovascular risk profile (level of evidence B)
(2) Resting ECG in all patients (level of evidence B)
Risk stratification using stress testing
Stress testing can take the form of exercise or pharmacological stress with or without imaging. Prognostic information obtained from stress testing relates not just to detection of ischaemia as a simple binary response, but also the ischaemic threshold, the extent and severity of ischaemia (for imaging techniques), and functional capacity (for exercise testing). Stress testing alone is insufficient to assess risk of future events. In addition to the limitations of the different techniques in the detection of myocardial ischaemia, however small, it must also be recognized that ischaemia per se is not the only factor which influences the likelihood of acute events. Several lines of evidence have shown that the majority of vulnerable plaques appear angiographically insignificant before their rupture, and may not impinge on coronary flow to reveal characteristic changes during exercise ECG or stress imaging. This may explain the occasional acute coronary event that occurs shortly after a negative stress test result. Risk stratification with the exercise test should be a part of a process that includes readily accessible data from clinical examination and should not take place in isolation. Thus the stress test is performed to provide additional information regarding the patient’s risk status.
Symptomatic patients with suspected or known CAD should undergo stress testing to assess the risk of future cardiac events unless cardiac catheterization is urgently indicated. However, no randomized trials of stress testing have been published, and therefore the evidence base consists of observational studies only. The choice of initial stress test should be based on the patient’s resting ECG, physical ability to perform exercise, local expertise, and available technologies. Exercise ECG. The exercise ECG has been extensively validated as an important tool in risk stratification in symptomatic patients with known or suspected coronary disease. The prognosis of patients with a normal ECG and a low clinical risk for severe CAD is excellent. In one study in which 37% of outpatients referred for non-invasive testing met the criteria for low risk fewer than 1% had LM stem artery disease or died within 3 years. Lower-cost options such as treadmill testing should therefore be used, whenever possible, for initial risk stratification, and only those with abnormal results should be referred to arteriography.
In the original description of this score in a population with suspected CAD, two-thirds of patients with scores indicating low-risk had a 4-year survival rate of 99% (average annual mortality rate 0.25%), and the 4% who had scores indicating high-risk had a 4-year survival rate of 79% (average annual mortality rate 5%). The combination of exercise and clinical parameters, with or without the use of scores such as the DTS, has been shown to be an effective method of discriminating between high- and low-risk groups within a population presenting with known or suspected coronary disease.
Stress echocardiography. Stress echocardiography may also be used effectively to stratify patients according to their risk of subsequent cardiovascular events and similarly has an excellent negative predictive value, in patients with a negative test having a hard event rate (death or MI) of <0.5%/year. The risk of future events is influenced both by the number of resting regional wall motion abnormalities and inducible wall motion abnormalities on stress echocardiography, with more resting abnormalities and a greater amount of inducible ischaemia associated with higher risk. Identification of a high risk cohort allows for appropriate further investigation and/or intervention.
Stress perfusion scintigraphy. SPECT perfusion scintigraphy is a useful method of non-invasive risk stratification, readily identifying those patients at greatest risk for subsequent death and MI. Normal stress myocardial perfusion images are highly predictive of a benign prognosis. Several studies involving thousands of patients have found that a normal stress perfusion study is associated with a subsequent rate of cardiac death and MI of less than 1% per year, which is nearly as low as that of the general population. The only exceptions would appear in patients with normal perfusion images with either a highrisk treadmill ECG score or severe resting LV dysfunction.
In contrast, abnormal findings on stress perfusion scintigraphy have been associated with severe CAD, and subsequent cardiac events. Large stress-induced perfusion defects, defects in multiple coronary artery territories, transient post-stress ischaemic LV dilatation, and in patients studied with
Th, increased lung uptake on postexercise or pharmacological stress images are all adverse prognostic indicators.
The results of planar and SPECT perfusion scintigraphy can be used to identify a ‘high-risk’ patient subset. These patients, who have a greater than 3% annual mortality rate, should be considered for early coronary arteriography, as their prognosis may be improved by revascularization. Exercise scintigraphy offers greater prognostic information than pharmacological stress imaging because of the information regarding symptoms, exercise tolerance, and haemodynamic response to exercise which is additive to that obtained from perfusion data alone.
Recommendations for risk stratification according to exercise stress ECG in stable angina in patients who can exercise
Class I
(1) All patients without significant resting ECG abnormalities undergoing initial evaluation (level of evidence B)
(2) Patients with stable coronary disease after a significant change in symptom level (level of evidence C)
Class IIa
(1) Patients post-revascularization with a significant deterioration in symptomatic status (level of evidence B)
Recommendations for risk stratification according to exercise stress imaging (perfusion or echocardiography) in stable angina in patients who can exercise
Class I
(1) Patients with resting ECG abnormalities, LBBB, .1mm ST-depression, paced rhythm, or WPW which prevent accurate interpretation of ECG changes during stress (level of evidence C)
(2) Patients with a non-conclusive exercise ECG, but intermediate or high probability of disease (level of evidence B)
Class IIa
(1) In patients with a deterioration in symptoms postrevascularization (level of evidence B)
(2) As an alternative to exercise ECG in patients where facilities, cost, and personnel resources allow (level of evidence B)
Recommendations for risk stratification according to pharmacological stress imaging (perfusion or echocardiography) in stable angina
Class I
(1) Patients who cannot exercise Other class I and II indications as for exercise stress imaging (perfusion or echocardiography) in stable angina in patients who can exercise, but where local facilities do not include exercise imaging.
Risk stratification using ventricular function
The strongest predictor of long-term survival is LV function. In patients with stable angina as LV ejection fraction (EF) declines, mortality increases. A resting EF of less than 35% is associated with an annual mortality rate greater than 3% per year.
Long-term follow-up data from the CASS registry showed that 72% of the deaths occurred in the 38% of the population that had either LV dysfunction or severe coronary disease. The 12-year survival rate of patients with EF >50% was 35–49% and <35% were 73, 54, and 21%, respectively (P< 0.0001). The prognosis of patients with a normal ECG and low clinical risk for severe CAD is, on the other hand, excellent. Ventricular function affords additional prognostic information to coronary anatomy, with reported 5-year survival rates of a man with stable angina and three-vessel disease ranging from 93% in those with normal ventricular function to 58% with reduced ventricular function. Impaired ventricular function may be inferred from extensive Q-wave on ECG, symptoms or signs of heart failure, or measured noninvasively by echocardiography, radionuclide techniques or contrast ventriculography at the time of coronary arteriography.
Clinical evaluation as outlined earlier may indicate which patients have heart failure, and thus at substantially increased risk for future cardiovascular events. However, the prevalence of asymptomatic ventricular dysfunction is not inconsiderable, and has been reported to be as high as twice that of clinical heart failure, with the presence of ischaemic heart disease a major risk factor for its occurrence.
Ventricular dimensions have been shown to contribute useful prognostic information which is incremental to the results of exercise testing in a stable angina population with 2-year follow-up. In a study of hypertensive patients without angina, the use of echocardiography to assess ventricular structure and function was associated with reclassification from medium/low risk to high risk in 37% of patients, and the European guidelines for the management of hypertension recommend an echocardiogram for patients with hypertension. Diabetic patients with angina also require particular attention. Echocardiography in diabetic individuals with angina has the advantage of identifying LVH and diastolic as well as systolic dysfunction, all of which are more prevalent in the diabetic population. Thus, an estimation of ventricular function is desirable in risk stratification of patients with stable angina, and an assessment for ventricular hypertrophy (by echocardiography or MRI), as well as assessment of ventricular function is particularly pertinent in patients with hypertension or diabetes. For most other patients the choice of investigation to determine ventricular function will be dependent on the other tests which have been performed or are planned, or the level of risk estimated by other methods. For example, in a patient who has a stress imaging test it may be possible to estimate ventricular function from this test without additional investigation, or a patient scheduled to have coronary arteriography on the basis of a strongly positive exercise test at low workload, in the absence of prior MI, or other indications for echocardiography, may have ventricular systolic function assessed at the time of arteriography.
Recommendations for risk stratification by echocardiographic evaluation of ventricular function in stable angina
Class I
(1) Resting echocardiography in patients with prior MI, symptoms or signs of heart failure, or resting ECG abnormalities (level of evidence B)
(2) Resting echocardiography in patients with hypertension (level of evidence B)
(3) Resting echocardiography in patients with diabetes (level of evidence C)
Class IIa
(1) Resting echocardiography in patients with a normal resting ECG without prior MI who are not otherwise to be considered for coronary arteriography (level of evidence C)
Risk stratification using coronary arteriography
Despite the recognized limitations of coronary arteriography to identify vulnerable plaques which are likely to lead to acute coronary events, the extent, severity of luminal obstruction, and location of coronary disease on coronary arteriography have been convincingly demonstrated to be important prognostic indicators in patients with angina.
Several prognostic indices have been used to relate disease severity to the risk of subsequent cardiac events; the simplest and most widely used is the classification of disease into one vessel, two vessel, three vessel, or LM CAD. In the CASS registry of medically treated patients, the 12-year survival rate of patients with normal coronary arteries was 91% compared with 74% for those with onevessel disease, 59% for those with two vessel disease and 50% for those with three vessel disease (P < 0.001). Patients with severe stenosis of the LM coronary artery have a poor prognosis when treated medically. The presence of severe proximal left anterior descending artery (LAD) disease also significantly reduces the survival rate. The 5-year survival rate with three-vessel disease plus greater than 95% proximal LAD stenosis was reported to be 54% compared with a rate of 79% with three-vessel disease without LAD stenosis. However, it should be appreciated that in these ‘older’ studies preventive therapy was not at the level of current recommendations regarding both lifestyle and drug therapy. Accordingly, absolute estimates of risk derived from these studies, in general, over-estimate the risk of future events.
Recommendations for risk stratification by coronary arteriography in patients with stable angina
Class I
(1) Patients determined to be at high risk for adverse outcome on the basis of non-invasive testing even if they present with mild or moderate symptoms of angina (level of evidence B)
(2) Severe stable angina (Class 3 of Canadian Cardiovascular Society Classification (CCS), particularly if the symptoms are inadequately responding to medical treatment (level of evidence B)
(3) Stable angina in patients who are being considered for major non-cardiac surgery, especially vascular surgery (repair of aortic aneurysm, femoral bypass, carotid endarterectomy) with intermediate or high risk features on non-invasive testing (level of evidence B)
Class IIa
(1) Patients with an inconclusive diagnosis oon-invasive testing, or conflicting results from different noninvasive modalities (level of evidence C)
(2) Patients with a high risk of restenosis after PCI if PCI has been performed in a prognostically important site (level of evidence C)
Treatment
Treatment of the acute attack
Patients should be advised to rest, at least briefly, from the activity which provoked the angina and advised regarding the use of sublingual nitrate for acute relief of symptoms. It is also useful to warn the patient of the need to protect against potential hypotension by sitting on the first number of occasions when taking sublingual nitrate and also other possible side-effects, particularly headache. The use of prophylactic nitrate to prevent predictable episodes of angina in response to exertion can be encouraged. Patients should be informed of the need to seek medical advice if angina persists for >10–20 min after resting and/ or is not relieved by sublingual nitrate.
All preventive measures, pharmacological and nonpharmacological, described in this document apply similarly to men and women, even if there is less documentation of health benefits among female compared with male patients with stable angina pectoris and the clinical presentation of the disease may differ between genders. Risk factors, clinical presentation, and the level of risk for serious cardiovascular complications should determine the need for preventive and therapeutic interventions, rather than the gender of the patient. Recommendations concerning hormone replacement therapy have changed and are commented upon subsequently.
Smoking
Cigarette smoking should be strongly discouraged, as there is abundant evidence that it is the most important reversible risk factor in the genesis of coronary disease in many patients. Cessation of smoking greatly improves both symptoms and prognosis. Patients often require special help in abandoning their addiction, and nicotine replacement therapy has proved effective and safe in helping patients with CAD to quit smoking.
Diet and alcohol
Dietary interventions are effective in the prevention of events in patients with established CAD, when properly implemented. Certain food types are to be encouraged such as fruit, vegetables, cereal, and grain products as well as skimmed dairy products, fish, and lean meat, many of which are major components of the Mediterranean diet. Patients should thus be encouraged to adopt a ‘Mediterranean’ diet, with vegetables, fruit, fish, and poultry being the mainstays. The intensity of change needed in the diet may be guided by the total and LDL cholesterol levels and other lipid abnormalities. Those who are overweight should be put on a weight reducing diet.
Alcohol in moderation may be beneficial, but excessive consumption is harmful, especially in patients with hypertension or heart failure. It has been difficult to develop public health recommendations on safe limits of alcohol use, but moderate alcohol consumption should not be discouraged.
Omega-3 fatty acids
Fish oils rich in omega-3 fatty acids (n-3 polyunsaturated fatty acids) are useful in the reduction of hypertriglyceridaemia, and in the GISSI-Prevenzione trial, supplementation with one fish oil capsule (Omacor) daily was shown to reduce the risk of sudden death in patients (85% men) with a recent MI. A detailed further analysis of the GISSI-Prevenzione trial showed an early reduction of cardiovascular death which was dependent on fewer sudden deaths. The effect was attributed to antiarrhythmic effects of omega-3 fatty acid supplementation, in agreement with previous experimental data. A meta-analysis of omega-3 fatty acid supplementation confirmed the effect on sudden death and showed a reduction of mortality, but concluded that reasonably large riskreductionwithsuchtherapycanonlybeexpected among high-risk patients, such as patients with a recent MI. A more recent meta-analysis of the effects of lipid-lowering therapies on mortality also confirmed the beneficial effect of n-3 fatty acids in secondary prevention. Patients with stable angina without high risk features should rarely be considered for omega-3 fatty acid supplementation. Dietary intervention to achieve fish consumption at least once weekly can, however, be more widely recommended.
Vitamins and antioxidants
Vitamin supplementation has not been shown to reduce cardiovascular risk in patients with CAD. In contrast to the above-mentioned findings with dietary intervention, several large stdies have failed to find benefits from pharmacological supplementation with antioxidant vitamins.
Hypertension, diabetes, and other disorders
Concomitant disorders should be managed appropriately. Particular attention should be given to control of elevated blood pressure, diabetes mellitus, and other features of the metabolic syndrome which increase the risk of progression of coronary disease. Of particular note, the Task Force report on CVD prevention suggests considering a lower threshold for institution of pharmacological therapy for hypertension (130/85) for patients with established CHD (which would include patients with angina and noninvasive or invasive confirmation of coronary disease). Patients with concomitant diabetes and/or renal disease should be treated with a blood pressure goal of <130/ 80 mm Hg. Diabetes is a strong risk factor for cardiovascular complications and should be managed carefully withgood glycaemic control and attention to other risk factors.
Multifactorial intervention in diabetic patients may indeed reduce both cardiovascular and other diabetic complications markedly. Recently, the addition of pioglitizone to other hypoglycaemic medication has been shown to reduce the incidence of death, non-fatal MI, or stroke (a secondary endpoint) in patients with type 2 diabetes and vascular disease by 16%; the primary composite endpoint, which included a number of vascular endpoints, was not significantly reduced. Anaemia or hyperthyroidism, if present, should be corrected.
Physical activity
Physical activity within the patient’s limitations should be encouraged, as it may increase exercise tolerance, reduce symptoms, and has favourable effects on weight, blood lipids, blood pressure, glucose tolerance, and insulin sensitivity. Advice on exercise must take into account the individual’s overall fitness and the severity of symptoms. An exercise test can act as a guide to the level at which an exercise programme can be initiated. Detailed recommendations on exercise prescription and on recreational and vocational activities are provided by the ESC Working Group on Cardiac Rehabilitation.
Psychological factors
Although the role of stress in the genesis of CAD is controver sial, there is no doubt that psychological factors are important in provoking attacks of angina. Furthermore, the diagnosis of angina often leads to excessive anxiety. Reasonable reassurance is essential, and patients may benefit from relaxation techniques and other methods of stress control. Appropriate programmes may reduce the need for drugs and surgery. A randomized controlled trial
of a self-management plan showed an apparent improvement in the psychological, symptomatic, and functional status of patients with newly diagnosed angina.
Car driving
In most countries, patients with stable angina are permitted to drive except for commercial public transport or heavy vehicles. Stressful driving conditions should be avoided.
Sexual intercourse
Sexual intercourse may trigger angina. Common sense will dictate that this should not be too physically or emotionally demanding. Nitroglycerin prior to intercourse may be helpful. Phosphodiesterase (PGE5) inhibitors such as sildenafil, tadafil, and vardenafil, used in the treatment of erectile dysfunction, may bestow benefits in terms of exercise duration and can be safely prescribed to men with CAD but should not be used in those receiving long-acting nitrates. The patient must be informed about the potentially harmful interactions between PGE5 inhibitors and nitrates or NO (nitric oxide) donors.
Employment
An assessment should always be made of the physical and psychological factors involved in an affected subject’s work (including housework). Patients should, if possible, be encouraged to continue in their occupation, with appropriate modifications, if necessary.
Pharmacological treatment of stable angina pectoris
The goals of pharmacological treatment of stable angina pectoris are to improve quality of life by reducing the severity and/or frequency of symptoms and to improve the prognosis of the patient. Measures of quality of life reflect disease severity and carry prognostic information if properly assessed. When selecting evidence-based strategies for pharmacological prevention of cardiac complications and death, one should consider the often benign prognosis of the patient with stable angina pectoris. Pharmacotherapy is a viable alternative to invasive strategies for the treatment of most patients with stable angina pectoris and was actually associated with fewer complications than surgery or PCI during a 1-year follow-up of the MASS-II study. An invasive treatment strategy may be reserved for patients at high risk or patients with symptoms that are poorly controlled by medical treatment. The intensity of preventive pharmacotherapy should be tailored to the individual risk of the patient, keeping in mind the relatively low risk of many patients with stable angina pectoris.
Pharmacological therapy to improve prognosis
Co-existing disorders such as diabetes and/or hypertension in patients with stable angina should be well controlled, dyslipidaemia should be corrected, and smoking cessation attempted (without or with pharmacological support). Statin and angiotensin-converting enzyme (ACE)-inhibitor treatment may provide protection above that which can be ascribed to their lipid and blood pressure lowering effects, respectively, and are discussed separately. In addition, antiplatelet treatment should always be considered for patients with ischaemic heart disease. Levels of evidence based on prognosis and symptom relief are provided for the recommended treatments for angina in the treatment algorithm illustrated in Figure 7.
Antithrombotic drugs. Antiplatelet therapy to prevent coronary thrombosis is indicated, due to a favourable ratio between benefit and risk in patients with stable CAD. Low-dose aspirin is the drug of choice in most cases, whereas clopidogrel may be considered for some patients. Because of the evolving story of increased cardiovascular risks with cyclooxygenase (COX)-2 inhibitor or NSAID treatment, as well as interactions between NSAIDs and aspirin, these drugs will also be commented upon from the cardiovascular perspective.
Statins lower cholesterol effectively, but mechanisms other than cholesterol synthesis inhibition, such as antiinflammatory and antithrombotic effects, may conribute to the cardiovascular risk reduction. In patients with stable angina, it has been shown that 7 days pretreatment with atorvastatin 40 mg/day compared with placebo before PCI reduced procedural myocardial injury, as assessed by biochemical markers. Such myocardial protection by short-term, high-dose atorvastatin treatment may be related to non-lipid effects of the statin treatment. Similar relative benefits of long-term statin therapy have been observed in patients with different pretreatment levels of serum cholesterol, even in the ‘normal’ range. Thus, recommendations to treat with statins may be guided as much by the patients level of cardiovascular risk as by the cholesterol level (within the normal to moderately elevated range). As for blood pressure (discussed subsequently), the risk associated with choles– terol increases log-linearly from low normal levels, and it is therefore difficult to evaluate the relative importances of cholesterol lowering and other effects of statin treatment for the treatment benefits observed. A recent meta-analysis of the effects of different lipid-lowering therapies on mor– tality concluded that statins and n-3 fatty acids reduced mortality, whereas fibrates, resins, niacin, and dietary interventions failed to do so; a tendancy towards reduced cardiac mortality was counterbalanced by an increase ion-cardiac mortality in the fibrate trials.
Current European Prevention guidelines suggest a target value of <4.5 mmol/L (175 mg/dL) for total cholesterol and 2.5 mmol/L (96 mg/dL) for LDL cholesterol in patients with established CHD or even those who remain at persistently high multifactorial risk (>5% risk of fatal cardiovascular events over 10 years). However, several studies have shown that C-reactive protein levels predict beneficial outcomes during statin therapy as well do cholesterol levels and that these two markers of statin responsiveness are additive. Such analyses of clinical trial data suggest that cholesterol-independent effects of statin therapy may be of clinical importance. Thus, patient selection based on cholesterol levels and therapy solely directed at cholesterol goals may not fully exploit the benefit of statin therapy. Statin therapy should always be considered for patients with stable CAD and stable angina, based on their elevated level of risk and evidence of benefit of cholesterol lowering within the normal range. Therapy should aim at statin dosages documented to reduce morbidity/mortality in clinical trials. If this dose is not sufficient to achieve the target total cholesterol and LDL levels as mentioned above, the dose of statin therapy may be increased as tolerated to achieve the targets. The daily statin dosages with solid documentation in the above-mentioned studies are simvastatin 40 mg, pravastatin 40 mg, and atorvastatin 10 mg. Recently, high-dose atorvastatin treatment (80 mg daily) has been shown to reduce the risk of cardiovascular events when compared with 10 mg atorvastatin or simvastatin ~24 mg in patients with stable CAD.
The increased efficacy of high-dose atorvastatin treatment was accompanied by six-fold increase (from 0.2 to 1.2%; P < 0.001) in enzymatic signs of liver damage, but no discernible increase in myalgia. High-dose atorvastatin therapy should be reserved for high-risk patients.
Statin treatment is associated with few side effects, but skeletal muscle damage (symptoms, CK elevations, and, rarely, rhabdomyolysis) may occur, and liver enzymes should be also monitored after initiation of therapy. Gastrointestinal disturbances may limit the dosage. If statins are poorly tolerated at high doses, or lipid control is not achieved with the highest statin dose, reduction of the statin dose and the addition of the cholesterol absorption inhibitor, ezetimibe, may afford adequate reduction of cholesterol. Effects on morbidity and mortality of such combination treatment have, however, not yet been documented.
Lipid-modifying drugs other than statins, e.g. fibrates, resins, or prolonged release nicotinic acid, and their combinations with statins and other hypolipidaemics may be needed to control the lipid levels among patients with severe dyslipidaemia. This is especially true of those with low levels of HDL cholesterol and high triglycerides. ACE-inhibitors. ACE-inhibitors are well established for the treatment of hypertension and heart failure, but have not been shown to confer better overall protection against the cardiovascular complications in hypertension, compared with that afforded by other antihypertensive drugs. ACE-inhibitors or angiotensin receptor blockers (ARBs) are recommended for the treatment of diabetic patients with microalbuminuria to prevent progression of renal dysfunction, and as first-line agents to treat blood pressure in diabetic patients.
Because of observed reductions in MI and cardiac mortality in trials of ACE-inhibitors for heart failure and post-MI, ACE-inhibitors have also been investigated as secondary preventive therapy for patients with coronary disease without heart failure. The HOPE study included high-risk patients with established CVD (coronary or non-coronary) or diabetes, and at least one other risk factor, and randomized them to treatment with ramipril or placebo for 5 years. The EUROPA study included patients with stable CAD, with a broad range of risk but without clinical heart failure, who were randomized to treatment with perindopril or placebo for 4.2 years. The PEACE study included patients with stable CAD without heart failure who were treated with trandolapril or placebo for 4.8 years. As shown in Figure 1, the annual cardiovascular mortality rates in the placebo groups ranged from 0.8% (PEACE) to 1.6% (HOPE). The differences in cardiovascular risk were associated with differences in therapy at baseline.
Treatment benefits with ACE-inhibition were thus smaller in PEACE than in HOPE or EUROPA. One possible explanation for this difference in outcomes might be differences between the three ACE-inhibitors and/or the relative dosages used. However, the dosage of trandolapril used in PEACE was associated with a significant 25% reduction of cardiovascular death and a 29% reduction of severe heart failure, but a lesser decrease ion-fatal MI (214%, NS) in consecutively enrolled post-MI patients with LV dysfunction in the TRACE study. Baseline blood pressure was lower (133/78 mmHg) in the PEACE population than in either of the other two studies. The rates of previous revascularization ranged from 44% (HOPE) to 72% (PEACE), and drug therapy at baseline differed between the studies. Lipid-lowering therapy was received by only 29% of patients in HOPE compared with 70% in PEACE; the corresponding figures were 76 vs. 96% for antithrombotic drug treatment and 40 vs. 60% for beta-blocker use. Conversely, calcium channel blocker (CCB) use at baseline was more common in the HOPE study. Overall, PEACE patients were at lower absolute risk of cardiovascular death than the HOPE or EUROPA patients. These differences in baseline risk and non-study-related therapy may have contributed importantly to the differences in cardiovascular outcome with ACE-inhibitor therapy.
The relative effects of ramipril and perindopril on cardiovascular outcome were similar in a high-risk population and an intermediate population, respectively, although for obvious reasons, the ARR was greater in the population at highest absolute risk (MICRO-HOPE). Pre-defined subgroup analysis of EUROPA and HOPE according to individual factors known to affect risk, such as age, diabetes, prior MI, non coronary vascular disease, and microalbuminuria, showed relative benefit of similar magnitude from therapy with ACE-inhibitor in almost all subgroups.
Beta-1 blockade by metoprolol or bisoprolol have been shown to effectively reduce cardiac events in patients with congestive heart failure. Carvedilol, a nonselective beta-blocker that also blocks alpha-1 receptors, also reduces risk of death and hospitalizations for cardiovascular causes in patients with heart failure.
Calcium channel blockers. Heart rate lowering CCBs may improve the prognosis of post-MI patients, as shown in the DAVIT II study for verapamil and in a subgroup analysis of patients without signs of heart failure in the MDPIT study for diltiazem. Also, in the INTERCEPT trial there was a trend towards a reduction in the primary endpoint of cardiac death, non-fatal re-infarction and refractory ischaemia, and a significant reduction of the need for revascularization among post-MI patients treated with diltiazem compared with placebo. CCBs are also effective antihypertensive agents without advantages over other blood pressure lowering drugs regarding clinical outcomes overall, but CCB treatment is associated with an increased risk of heart failure.
Prognostic documentation in stable CAD has not been available for dihydropyridine CCBs until recently. Older trials of short-acting nifedipine showed no benefit regarding hard endpoints among patients with CAD, and even an increased risk of dying with high doses of the drug. This sparked an intense ‘calcium antagonist debate’ which pointed out the inappropriateness of treatment with short-acting vasodilator drugs such as dihydropyridine CCBs. A eta-analysis of the safety of nifedipine in stable angina ectoris suggested that the drug was safe.
The recently published ACTION trial, which compared treatment with long-acting nifedipine and placebo during 4.9 years of follow-up in 7665 patients with stable angina pectoris, is adequately powered for assessments of morbidity and mortality. The ACTION trial showed no benefit of treatment with long-acting nifedipine compared with placebo with regard to composite endpoints including death, MI, refractory angina, debilitating stroke, and heart failure. Nifedipine treatment tended to increase the need for peripheral revascularization (HR 1.25; P = 0.073), but reduced the need for coronary bypass surgery (HR 0.79; P = 0.0021). The authors concluded that nifedipine treatment is safe and reduces the need for coronary interventions, but has not been shown to have beneficial effects on hard endpoints such as death and MI.
A major drawback with the ACTION trial is the liberal inclusion of patients with high blood pressure, as the blood pressure lowering effects of nifedipine compared with placebo would be expected to provide health benefits unrelated (or in addition) to those possibly afforded by the antiischaemic or other effects of calcium antagonism. Thus, ACTION included patients with blood pressures <200/105 mmHg, and 52% of the patients had blood pressures ≥140/90 mmHg at baseline, even though the average blood pressure was 137/80 mmHg. The proportion with blood pressure ≥140/90 mmHg was reduced to 35% in the nifedipine group and 47% in the placebo group, indicating that attempts to achieve similar blood pressure control among all participants in the study were insufficient. On average, nifedipine treatment caused a slight, but significant and sustained elevation of heart rate by approximately 1 bpm, and reduced blood pressure by ~6/3 mmHg. Subgroup analysis of the ACTION study showed significant benefit of nifedipine treatment among patients with elevated blood pressure at baseline but a tendency towards unfavourable results among those who had blood pressures below 140/90 mmHg. A 6 mmHg reduction of systolic blood pressure would be expected to reduce major cardiovascular events by some 25% according to the meta-regression analysis of Staessen et al., and this effect should not be restricted to clearly hypertensive patients. Thus, the findings of ACTION may not be compatible with the benefits one might expect due to the reduction of blood pressure.
The CAMELOT study compared treatment with amlodipine, enalapril, or placebo in 1991 patients with stable CAD and normal blood pressure during 2 years of follow-up. As discussed earlier, amlodipine and enalapril treatment lowered blood pressure equally and seemed to reduce the incidence of ‘hard’ endpoints similarly, although these results were not significant.
The abovementioned APSIS and TIBET studies were not placebo-controlled or ‘powered’ to determine effects on mortality, but show no major differences between betablockers and CCBs with regard to cardiovascular morbidity and mortality during long-term treatment of stable angina pectoris. A meta-analysis of 72 trials comparing calcium antagonists and beta-blockers in stable angina pectoris indicated similar outcomes with the two drug classes. However, the mean duration of the studies in this meta-analysis was only 8 weeks. A meta-analysis restricted to six larger trials reached a similar conclusion.
To conclude, there is no evidence to support the use of CCBs for prognostic reasons in uncomplicated stable angina, although heart rate lowering CCBs may be used as an alternative to beta-blockers post-MI in patients without heart failure who do not tolerate beta-blockers.
Recommendations for pharmacological therapy to improve prognosis in patients with stable angina
Class I
(1) Aspirin 75 mg daily in all patients without specific contraindications (i.e. active GI bleeding, aspirin allergy, or previous aspirin intolerance) (level of evidence A)
(2) Statin therapy for all patients with coronary disease (level of evidence A)
(3) ACE-inhibitor therapy in patients with coincident indications for ACE-inhibition, such as hypertension, heart failure, LV dysfunction, prior MI with LV dysfunction, or diabetes (level of evidence A)
(4) Oral beta-blocker therapy in patients post-MI or with heart failure (level of evidence A)
Class IIa
(1) ACE-inhibitor therapy in all patients with angina and proven coronary disease (level of evidence B)
(2) Clopidogrel as an alternative antiplatelet agent in patients with stable angina who cannot take aspirin (e.g. aspirin allergic) (level of evidence B)
(3) High dose statin therapy in high-risk (.2% annual CV mortality) patients with proven coronary disease (level of evidence B)
Class IIb
(1) Fibrate therapy in patients with low HDL and high triglycerides who have diabetes or the metabolic syndrome (level of evidence B)
(2) Fibrate or nicotinic acid as adjunctive therapy to statin in patients with low HDL and high triglycerides at high risk (.2% annual CV mortality) (level of evidence C)
Pharmacological treatment of symptoms and ischaemia
Symptoms of angina pectoris and signs of ischaemia (also silent ischaemia) may be reduced by drugs that reduce myocardial oxygen demand and/or increase blood flow to the ischaemic area. Commonly used anti-anginal drugs are beta-blockers, calcium antagonists, and organic nitrates.
Short-acting nitrates. Rapidly acting formulations of nitroglycerin provide effective symptom relief in connection with attacks of angina pectoris, and may be used for ‘situational prophylaxis’. The pain relieving and antiischaemic effects are related to venodilatation and reduced diastolic filling of the heart (reduced intracardiac pressure), which promotes subendocardial perfusion. Coronary vasodilatation and antagonism of coronary vasospasm may contribute. Nitrate tolerance (see below) blunts responses to short-acting nitroglycerin, and should be avoided.
There is marked first-pass metabolism of orally administered nitroglycerin. Absorption via the oral mucosa is rapid and by-passes the liver, leading to increased bioavailability. Thus, rapid and efficient symptom relief by nitroglycerin may be achieved with sublingual or buccal tablets, or an oral spray. Buccal tablets have a longer duration of action and may be useful for situational prophylaxis. Nitroglycerin tablets decay when exposed to air, and opened containers should be discarded within 3 months; spray formulations are stable.
Nitroglycerin causes dose-dependent vasodilator sideeffects, such as headache and flushing. Overdosing may cause postural hypotension and reflexogenic cardiac sympathetic activation with tachycardia, leading to ‘paradoxical’ angina. An attack of angina that does not respond to short-acting nitroglycerin should be regarded as a possible MI. Thus, patients should be carefully instructed about how to use short-acting nitroglycerin. Short-acting nitrate consumption is a simple and good measure of treatment effects with other anti-anginal drugs.
Long-acting nitrates. Treatment with long-acting nitrates reduces the frequency and severity of anginal attacks, and may increase exercise tolerance. Long-acting nitrate treatment is only symptomatic, as studies after MI have failed to show prognostic benefit of such treatment.
Side effects are mainly related to vasodilatation, i.e. headaches and flushing, as described earlier.
Several long-acting nitrates are available. Isosobide dinitrate (ISDN) has an intermediate duration of action, and requires more than once daily dosing. Isosorbide5-mononitrate (ISMN) is supplied in various formulations that provide extended action of a suitable duration (see below). Nitroglycerin patches for transdermal treatment allow full control of the duration of action, but are more expensive than ISDN or ISMN.
Nitrate tolerance may develop wheitrate levels are continuously maintained above a certain threshold level, and results in poorer protection against angina attacks and resistance to the pain relieving effects of short-acting nitroglycerin. Thus, patients treated with long-acting nitrates should have a ‘nitrate-free’ interval each day to preserve the therapeutic effects. This may be achieved with appropriate timing of doses of intermediate acting ISDN or with formulations of ISMN that provide a suitable plasma concentration profile. Continuous transdermal nitroglycerin therapy is not effective and patients should remove the patches during part of the day or at night to achieve the nitrate-free interval; a decreased anginal threshold and rebound angina may, however, occur when patches are removed. Transdermal nitroglycerin has been more clearly associated with rebound ischaemia than oral longacting nitrate treatment.
Beta-blockers. Beta-blockers are well documented for the prevention of anginal symptoms and ischaemia. They reduce oxygen demand by reducing heart rate andn contractility, and by reducing blood pressure. Resting and exercise heart rate will be reduced by most beta-blockers except those with partial agonist activity where only the exercise heart rate is reduced. Perfusion of ischaemic areas may be improved by prolonging diastole (i.e. the perfusion time), and by ‘reverse coronary steal’ due to increased vascular resistance ion-ischaemic areas. Beta-blockers are also well established in the treatment of hypertension.
Beta-1 selective antagonists are as effective as nonselective antagonists, indicating that the beta-1 selective sympathetic neurotransmitter, noradrenaline, is the primary beta-adrenergic target for inhibition. Beta-1 selective agents are preferred due to advantages concerning side-effects and precautions compared with non-selective beta-blockers. Commonly used beta-1 blockers with good documentation as anti-anginal drugs are metoprolol, atenolol, and bisoprolol. The anti-anginal and anti-ischaemic effects are related to the degree of cardiac beta-1 adrenoceptor blockade, i.e. to the plasma concentration of the drug, whereas the blood pressure lowering effect in hypertension is not. To achieve 24 h efficacy a beta-1 blocker with a long half-life (e.g. bisoprolol) or a formulation providing an extended plasma concentration profile (e.g. metoprolol CR) may be used. For atenolol (with a plasma half-life of 6–9 h), twice daily dosing may be better, but increasing the dose also extends the duration of action. Target doses for full anti-anginal effects are: bisoprolol 10 mg od, metoprolol CR 200 mg od, atenolol 100 mg/day od (or 50 mg bid). The degree of beta-blockade may be assessed by exercise testing. Beta-blockers are effective anti-anginal drugs which increase exercise tolerance, and decrease symptoms and short-acting nitrate consumption. However, symptoms may increase on beta-blockade in patients with vasospastic angina.
Calcium channel blockers. CCBs are also well established anti-anginal agents. This is a heterogeneous class of drugs which dilatate coronary and other arteries by inhibiting calcium influx via L-type channels. Non-selective or heart rate lowering CCBs (verapamil and diltiazem) also to some degree reduce myocardial contractility, heart rate, and A-V nodal conduction. Even vasoselective dihydropyridine CCBs (e.g. nifedipine, amlodipine, and felodipine) may cause some cardiodepression, but this is counteracted by reflexogenic cardiac sympathetic activation with slight increases in heart rate which subside over time. However, signs of sympathetic activation may be seen even after months of treatment with a dihydropyridine CCB.
Long-acting CCBs (e.g. amlodipine) or sustained release formulations of short-acting CCBs (e.g. nifedipine, felodipine, verapamil, and diltiazem) are preferred, to minimize fluctuations of plasma concentrations and cardiovascular effects. Side effects are also concentration-dependent, and mainly related to the arterial vasodilator responses (headache, flushing, and ankle oedema). These effects are more pronounced with dihydropyridine CCBs. Verapamil may cause constipation.
The anti-anginal effects of CCBs are related to decreased cardiac work due to systemic vasodilatation, as well as coronary vasodilatation and counteraction of vasospasm. CCBs are especially effective in patients with vasospastic (prinzmetal) angina, but in some patients CCBs may, however, increase ischaemia.
The anti-anginal and anti-ischaemic effects of CCBs are additive to those of beta-blockers in many, but not all patients. Dihydropyridine CCBs are suitable for combination with beta-blockers, which counteract the reflexogenic cardiac sympathetic activation. Heart rate lowering CCBs may cause conduction disturbances in predisposed patients treated with beta-blockers. All CCBs may precipitate heart failure in predisposed patients. Attempts to use dihydropyridine CCBs for vasodilator treatment of heart failure have not been successful. However, amlodipine may be used for the treatment of angina in patients with compensated heart failure if not controlled by other therapy (i.e. nitrates, beta-blockers).
Comparison of beta-blocker and calcium antagonist (CCB) treatment in stable angina. The IMAGE study compared patients with stable angina treated with metoprolol CR 200 mg od or nifedipine SR 20 mg bid during 6 weeks (140 patients in each group). Both metoprolol and nifedipine prolonged exercise tolerance over baseline levels, with greater improvement in patients receiving metoprolol (P , 0.05). Responses to the two drugs were variable, and were difficult to predict. In the APSIS study, treatment with verapamil SR for 1 month was slightly more effective than metoprolol CR in increasing exercise tolerance. However, although exercise-induced ischaemia was predictive of cardiovascular events in the study, short-term treatment effects on exercise-induced ischaemia did not independently predict improvement in long-term outcome. This highlights the important difference between treatment of symptoms and ischaemia and treatment aimed prognosis. Severity of ischaemia on baseline assessment acts as a marker of the underlying severity of coronary disease. But it is the severity of disease which influences the likelihood of plaque destabilization, and the propensity to and severity of thrombotic complications if and when plaque becomes unstable, factors which are not modified by traditional anti-ischaemic agents.
Thus, in the absence of prior MI, the available data suggest that the choice between a beta-blocker and a CCB for anti-anginal treatment may be guided by individual tolerance and the presence of other disease and co-treatment. If these factors are equally weighted, a beta-blocker is recommended as the first choice.
Other agents. Sinus node inhibitors, such as ivabradine, act by selectivity inhibiting the cardiac pacemaker current If, and have negative chronotropic effects both at rest and during exercise. If inhibition has proven anti-anginal efficacy and ivabradine may be used as an alternative agent in patients who do not tolerate beta-blockade. It has been licenced by the EMEA for this purpose.
Metabolically acting agents protect from ischaemia by increasing glucose metabolism relative to that of fatty acids. Trimetazidine and ranolazine are both considered as metabolic anti-anginal drugs. However, ranolazine has also more recently been shown to be an inhibitor of the late sodium current, which is activated in case of ischaemia, leading to calcium overload of the ischaemic myocardium, decreased compliance, increased LV stiffness, and compression of the capillaries. The inhibition of the late sodium current by ranolazine reverses these effects, and prevents calcium overload, and the subsequent conse uences thereof.
Both trimetazidine and ranolazine have been shown to have anti-anginal efficacy. They may be used in combination therapy with haemodynamically acting agents, as their primary effect is not through reduction in heart rate or blood pressure. Trimetazidine has been available for several years, but not in all countries. Ranolazine, although under intensive investigation is not yet licenced for use by the EMEA. Whether these drugs influence the prognosis of patients with stable angina has not been determined.
Molsidomine is a vasodilator with an action similar to that of organic nitrates and in the appropriate dosage is an effective anti-ischaemic and anti-anginal agent. It is not available in all countries.
Recommendations for pharmacological therapy. Antianginal drug treatment should be tailored to the needs of the individual patient, and should be monitored individually. Short-acting nitrate therapy should be prescribed for all patients for immediate relief of acute symptoms as tolerated. Although different types of drugs have been shown to have additive anti-anginal effects in clinical trials, this may not necessarily be so in the individual patient. More intense anti-anginal treatment may also cause problems, as it has been shown that three anti-anginal drugs may provide less symptomatic protection than two drugs. Thus, the dosing of one drug should be optimized before adding another one, and it is advisable to switch drug combinations before attempting a three drug regimen. Poor adherence is always a factor to consider when drug therapy is unsuccessful.
Recommendations for pharmacological therapy to improve symptoms and/or reduce ischaemia in patients with stable angina
Class I
(1) Provide short-acting nitroglycerin for acute symptom relief and situational prophylaxis, with appropriate instructions on how to use the treatment (level of evidence B)
(2) Test the effects of a beta-1 blocker, and titrate to full dose; consider the need for 24 h protection against ischaemia (level of evidence A)
(3) In case of beta-blocker intolerance or poor efficacy attempt monotherapy with a CCB (level of evidence A), long-acting nitrate (level of evidence C), or nicorandil (level of evidence C)
(4) If the effects of beta-blocker monotherapy are insufficient, add a dihydropyridine CCB (level of evidence B)
Class IIa
(1) In case of beta-blocker intolerance try sinus node inhibitor (level of evidence B)
(2) If CCB monotherapy or combination therapy (CCB with beta-blocker) is unsuccessful, substitute the CCB with a long-acting nitrate or nicorandil. Be careful to avoid nitrate tolerance (level of evidence C)
Class IIb
(1) Metabolic agents may be used, where available, as add-on therapy, or as substitution therapy when conventional drugs are not tolerated (level of evidence B)
Consider triple therapy only if optimal two drug regimens are insufficient, and evaluate the effects of additional drugs carefully. Patients whose symptoms are poorly controlled on double therapy should be assessed for suitability for revascularization, as should those who express a strong preference for revascularization rather than pharmacological therapy. The ongoing need for medication to improve prognosis irrespective of revascularization status, and the balance of risk and benefit on an individual basis, should be explained in detail. Despite the array of therapeutic options outlined, the management of refractory angina continues to pose a challenge, and management options in such cases are outlined in a separate section below.
Special therapeutic considerations: cardiac Syndrome X and vasospastic angina
Treatment of Syndrome X. Treatment should focus on symptomatic relief. As nitrates are effective in about half of the patients, it is reasonable to start treatment with long-acting nitrates. If symptoms persist, calcium antagonists and b-blockers, which are beneficial in Syndrome X patients, may be added. Although a-adrenergic blockade increases vasodilator reserve in patients with Syndrome X, a-adrenergic blocking agents are clinically inefficient. There are reports that other drugs such as nicorandil and trimetazidine might be helpful in some patients.
ACE-inhibitors and statins are helpful to reverse underlying endothelial dysfunction. Thus, these drugs should be actively considered for patients with Syndrome X as part of their risk factor management, and there are some data to suggest that ACE-inhibitors and statins may also be beneficial in reducing exercise-induced ischaemia in this population.
The challenge of achieving long-lasting therapeutic effects in patients with Syndrome X requires a multidisciplinary approach. This might include analgesic intervention using imipramine or aminophylline, psychological intervention, electrostimulation techniques, and physical training. Some studies of transdermal hormone replacement therapy in post-menopausal patients have shown an improvement in endothelial function and symptoms, but in the light of recent trials documenting adverse cardiovascular outcomes with the use of HRT, caution is advised in prescription of HRT for this purpose.
Recommendations for pharmacological therapy to improve symptoms in patients with Syndrome X
Class I
(1) Therapy with nitrates, b-blockers, and calcium antagonists alone or in combination (level of evidence B)
(2) Statin therapy in patients with hyperlipidaemia (level of evidence B)
(3) ACE inhibition in patients with hypertension (level of evidence C)
Class IIa
(1) Trial of therapy with other anti-anginals including nicorandil and metabolic agents (level of evidence C)
Class IIb
(1) Aminophylline for continued pain, despite Class I measures (level of evidence C)
(2) Imipramine for continued pain, despite Class I measures (level of evidence C)
Treatment of vasospastic angina. Removal of precipitating factors such as cessation of smoking is essential. The main elements of drug therapy are nitrates and calcium antagonists. Although nitrates are highly effective in abolishing acute vasospasm, they are not as successful in preventing attacks of resting angina. CCBs are more effective in alleviating the signs and symptoms of coronary spasm and treatment should be aimed at using high doses (up to 480 mg/d verapamil, up to 260 mg/d diltiazem, up to 120 mg/d nifedipine). However, calcium antagonists achieve a complete resolution of symptoms in only 38% of patients. In most patients, a combination therapy with long-acting nitrates and high doses of calcium antagonists will result in an improvement of symptoms. In patients with resistant symptoms, addition of a second calcium antagonist of another class may be successful. Medical treatment seems to be more effective in women and in patients with ST-elevation during provocation testing.
The role of a-blockers is controversial but occasional therapeutic benefit has been reported. Nicorandil, a potassium channel activator, may also be useful in occasional patients with refractory vasospastic angina. Reports of success in treating drug-resistant focal vasospasm by coronary artery stenting exist, but this approach is not advocated for widespread application. CABG is not indicated because spasm distal to the anastomosis may occur. Spontaneous remission of spasmodicity occurs in about half of western people following medical treatment for at least 1 year. Thus, it is acceptable to taper and discontinue treatment 6–12 months after angina has disappeared on drug treatment. If vasospasm occurs in association with significant coronary disease, guideline recommendations for treatments to improve prognosis and secondary prevention should also be adhered to.
Recommendations for pharmacological therapy of vasospastic angina
Class I
(1) Treatment with calcium antagonists and if necessary nitrates in patients whose coronary arteriogram is normal or shows only non-obstructive lesions (level of evidence B)
Exams and Tests
Your health care provider will do a physical exam and measure your blood pressure. Tests that may be done to diagnose or rule out angina include:
· Coronary risk profile (special blood tests)
· ECG
· Exercise tolerance test (stress test or treadmill test)
· Nuclear medicine (thallium) stress test
· Stress echocardiogram
Treatment
The options for treating angina include lifestyle changes, medications, and procedures such as coronary angioplasty or stent placement and coronary artery bypass surgery.
You and your doctor should agree on a plan for treating your angina on a daily basis. This should include:
· What medicines you should be taking to prevent angina
· What activities are okay for you to do, and which ones are not
· What medicines you should take when you have angina
· What are the signs that your angina is getting worse
· When you should call the doctor or 911
MEDICATIONS
You may be asked to take one or more medicines to treat blood pressure, diabetes, or high cholesterol levels. Follow your doctor’s directions closely to help prevent your angina from getting worse.
Nitroglycerin pills or spray may be used to stop chest pain.
Taking aspirin and clopidogrel (Plavix) or prasugrel (Effient) helps prevent blood clots from forming in your arteries, and reduces your risk of having a heart attack. Ask your doctor whether you should be taking these medications.
Your doctor may give you one or more medicines to help prevent you from having angina.
· ACE inhibitors to lower blood pressure and protect your heart
· Beta-blockers to lower heart rate, blood pressure, and oxygen use by the heart
· Calcium channel blockers to relax arteries, lower blood pressure, and reduce strain on the heart
· Nitrates to help prevent angina
· Ranolazine (Ranexa) to treat chronic angina
NEVER STOP TAKING ANY OF THESE DRUGS ON YOUR OWN. Always talk to your doctor first. Stopping these drugs suddenly can make your angina worse or cause a heart attack. This is especially true of anti-clotting drugs (aspirin, clopidogrel, and prasugrel).
Your doctor may recommend a cardiac rehabilitation program to help improve your heart’s fitness.
Unstable Angina
Unstable angina is a condition in which your heart doesn’t get enough blood flow and oxygen. It may lead to a heart attack.
Angina is a type of chest discomfort caused by poor blood flow through the blood vessels (coronary vessels) of the heart muscle (myocardium).
Causes
Coronary artery disease due to atherosclerosis is by far the most common cause of unstable angina. Atherosclerosis is the buildup of fatty material called plaque along the walls of the arteries. This causes arteries to become narrowed and less flexible. The narrowing interrupts blood flow to the heart, causing chest pain.
People with unstable angina are at increased risk of having a heart attack.
Rare causes of angina are:
· Abnormal function of tiny branch arteries without narrowing of larger arteries (called microvascular dysfunction or Syndrome X)
Risk factors for coronary artery disease include:
· Diabetes
· Family history of early coronary heart disease — a close relative such as a sibling or parent had heart disease before age 55 (in a man) or before age 65 (in a woman)
· High LDL cholesterol
· Low HDL cholesterol
· Male gender
· Not getting enough exercise
· Obesity
· Older age
· Smoking
Symptoms
Symptoms of angina may include:
· Chest pain that you may also feel in the shoulder, arm, jaw, neck, back, or other area
· Discomfort that feels like tightness, squeezing, crushing, burning, choking, or aching
· Discomfort that occurs at rest and does not easily go away when you take medicine
· Shortness of breath
· Sweating
With stable angina, the chest pain or other symptom only occurs with a certain amount of activity or stress. The pain does not occur more often or get worse over time.
Unstable angina is chest pain that is sudden and often gets worse over time. You may be developing unstable angina if the chest pain:
· Starts to feel different, is more severe, comes more often, or occurs with less activity or while you are at rest
· Lasts longer than 15 – 20 minutes
· Occurs without cause (for example, while you are asleep or sitting quietly)
· Does not respond well to a medicine called nitroglycerin
· Occurs with a drop in blood pressure or shortness of breath
Unstable angina is a warning sign that a heart attack may happen soon. It needs to be treated right away. If you have any type of chest pain, see your doctor.
Exams and Tests
The doctor will perform a physical examination and check your blood pressure. The doctor may hear abnormal sounds, such as a heart murmur or irregular heartbeat, when listening to your chest with a stethoscope.
Tests for angina include:
· Blood tests to show if you have heart tissue damage or are at a high risk for heart attack, including troponin I and T-00745, creatine phosphokinase (CPK), and myoglobin
· ECG
· Stress tests
o Exercise tolerance test (stress test or treadmill test)
· Coronary angiography (taking pictures of the heart arteries using x-rays and dye) — this is the most direct test to diagnose heart artery narrowing
Coronary Artery Spasm
Coronary artery spasm is a temporary, suddearrowing of one of the coronary arteries (the arteries that supply blood to the heart). The spasm slows or stops blood flow through the artery and starves part of the heart of oxygen-rich blood.
Causes
The spasm often occurs in coronary arteries that have not become hardened due to plaque buildup (atherosclerosis). However, it also can occur in arteries with plaque buildup.
These spasms are due to a squeezing of muscles in the artery wall. They usually occur in just one area of the artery. The coronary artery may appear normal during testing, but it does not functioormally.
About 2% of patients with angina (chest pain and pressure) have coronary artery spasm.
Coronary artery spasm occurs most commonly in people who smoke or who have high cholesterol or high blood pressure. It may occur without cause, or it may be triggered by:
· Alcohol withdrawal
· Emotional stress
· Exposure to cold
· Medications that cause narrowing of the blood vessels (vasoconstriction)
· Stimulant drugs such as amphetamines and cocaine
Cocaine use and cigarette smoking can cause severe spasms of the arteries, and can cause the heart to work harder. In many people, coronary artery spasm may occur without any other heart risk factors (such as smoking, diabetes, high blood pressure, and high cholesterol).
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Symptoms
Spasm may be “silent” — without symptoms — or it may result in chest pain or angina. If the spasm lasts long enough, it may even cause a heart attack.
The main symptom is a type of chest pain called angina, which most often is felt under the chest bone (sternum) or left side of the chest, and is described as:
· Constricting
· Crushing
· Pressure
· Squeezing
· Tightness
It is usually severe. The pain may spread to the neck, jaw, shoulder, or arm.
The pain of coronary artery spasm:
· Often occurs at rest
· May occur at the same time each day, usually between midnight and 8:00 AM
· Lasts from 5 to 30 minutes
The person may lose consciousness.
Unlike angina that is caused by hardening of the coronary arteries, chest pain and shortness of breath due to coronary artery spasm are ofteot present when you walk or exercise
Exams and Tests
Tests to diagnose coronary artery spasm may include:
· ECG
· Echocardiography
Treatment
The goal of treatment is to control chest pain and prevent a heart attack. A medicine called nitroglycerin can relieve an episode of pain.
Your health care provider may prescribe other medications to prevent chest pain. You may need a type of medicine called a calcium channel blocker long-term. Your doctor may prescribe long-acting nitrates along with the calcium channel blocker.
Beta-blockers are another type of medication that may be used. However, beta-blockers may make the condition worse and may be harmful if used with cocaine.
Outlook (Prognosis)
Coronary artery spasm is a chronic condition. However, treatment usually helps control symptoms.
The disorder may be a sign that you have a high risk for heart attacks or potentially deadly irregular heart rhythms (arrhythmias). The outlook is generally good if you follow your doctor’s treatment recommendations and avoid certain triggers.
The hemodynamic findings are related directly to the extent of necrosis or scarring of the myocardium. In mild infarction, toe hemodynamics may be normal. With more severe disease, there may be a raised left ventricular end-diastolic pressure with associated increase in the pulmonary artery diastolic pressure, decreased cardiac output, and decreased ejection fraction. When the patient is hypotensive or in shock, the cardiac output is considerably reduced in conjunction with evidences of left ventricular failure and a high left ventricular filling pressure. The “wedge” and left ventricular diastolic pressure may be raised, with no abnormality in the right ventricular diastolic pressure or the right atrial pressure; thus, the superior Vena cava or right atrial pressures are often misleading because they do not reflect left ventricular events. They are, however, valuable if the pressures are very low, indicating the possibility of hypovolemia; the response to volume loads may be helpful in producing an increased cardiac output. The presence of a large V wave in the pulmonary wedge pressure pulse is helpful in diagnosing acute mitral insufficiency due to papillary muscle dysfunction in patients who abruptly worsen, with development of cardiac failure. Similarly, raised oxygen content in the right ventricle under similar circumstances helps in diagnosis of perforated ventricular septum.
Clinical Findings
History: Most patients with angina pectoris report of retrosternal chest discomfort rather than frank pain. The former is usually described as a pressure, heaviness, squeezing, burning, or choking sensation. Anginal pain may be localized primarily in the epigastrium, back, neck, jaw, or shoulders. Typical locations for radiation of pain are arms, shoulders, and neck. Typically, angina is precipitated by exertion, eating, exposure to cold, or emotional stress. It lasts for approximately 1-5 minutes and is relieved by rest or nitroglycerin. Chest pain lasting only a few seconds is not usually angina pectoris. The intensity of angina does not change with respiration, cough, or change in position. Pain above the mandible and below the epigastrium is rarely anginal iature.
Ask patients about the frequency of angina, severity of pain, and number of nitroglycerin pills used during angina episodes.
Angina decubitus is a variant of angina pectoris that occurs at night while the patient is recumbent. Some have suggested that it is induced by an increase in myocardial oxygen demand caused by expansion of the blood volume with increased venous return during recumbency.
The Canadian Cardiovascular Society grading scale is used for classification of angina severity, as follows:
Class I – Angina only during strenuous or prolonged physical activity
Class II – Slight limitation, with angina only during vigorous physical activity
Class III – Symptoms with everyday living activities, ie, moderate limitation
Class IV – Inability to perform any activity without angina or angina at rest, ie, severe limitation
The New York Heart Association classification is also used to quantify the functional limitation imposed by patients’ symptoms, as follows:
Class I – No limitation of physical activity (Ordinary physical activity does not cause symptoms.)
Class II – Slight limitation of physical activity (Ordinary physical activity does cause symptoms.)
Class III – Moderate limitation of activity (Patient is comfortable at rest, but less than ordinary activities cause symptoms.)
Class IV – Unable to perform any physical activity without discomfort, therefore severe limitation (Patient may be symptomatic even at rest.)
Unstable angina is defined as new-onset angina (ie, within 2 mo of initial presentation) of at least class III severity, significant recent increase in frequency and severity of angina, or angina at rest.
Physical:
For most patients with stable angina, physical examination findings are normal. Diagnosing secondary causes of angina, such as aortic stenosis, is important.
A positive Levine sign (characterized by the patient’s fist clenched over the sternum when describing the discomfort) is suggestive of angina pectoris.
Look for physical signs of abnormal lipid metabolism (eg, xanthelasma, xanthoma) or of diffuse atherosclerosis (eg, absence or diminished peripheral pulses, increased light reflexes or arteriovenous nicking upon ophthalmic examination, carotid bruit).
Examination of patients during the angina attack may be more helpful. Useful physical findings include third and/or fourth heart sounds due to LV systolic and/or diastolic dysfunction and mitral regurgitation secondary to papillary muscle dysfunction.
Pain produced by chest wall pressure is usually of chest wall origin.
1. Premonitory pain-Over one-third of patients give a history of alteration the pattern of angina, sudden onset of typical or atypical angina, or unusual “indigestion” felt in the chest.
2. Pain of infarction-This may begin during rest (even in sleep) or activity. It is similar to angina in location and radiation but is more severe, does not subside with rest, and builds up rapidly or in waves to maximum intensity in the space of a few minutes or longer. Nitroglycerin has little effect. The pain may last for hours if unrelieved by narcotics and is often unbearable. Patients break out in a cold sweat, feel weak and apprehensive; and move about, seeking a position of comfort. They prefer not to lie quietly. Lightheadedness, syncope, dyspnea, orthopnea, cough, wheezing, nausea and vomiting, or abdominal bloating may be present singly or in any combination.
3. Painless infarction-In 5-15% of cases, pain is absent or minor and is overshadowed by the immediate complications, notably acute pulmonary edema or rapidly developing heart failure, profound weakness, shock, syncope, or cerebral thrombosis.
B. Signs: Physical findings are highly variable; the presence of rales, gallop rhythm, tachycardia, arrhythmia or bradycardia, and hypotension correlate well with hemodynamic and clinical evidences of the severity of the attack and the extent of the necrosed myocardium.
1. Shock. Shock may be described as a systolic blood pressure below
2. Cardiac effects-In the severe attack, the first and second heart sounds are faint, are often indistinguishable on auscultation, and assume the so-called “tic-tac” quality. Gallop rhythm, distended neck veins, and basal rales are often present. Acute pulmonary edema or progressive congestive failure may dominate the picture. In less severe attacks, examination is normal or there may be diminished intensity of the first sound or low systolic blood pressure; arrhythmia, hypoxemia, radiologic evidence of pulmonary venous congestion, and echocardiographic evidence of left ventricular distention may be present. Pericardial friction rub appears in 20% of cases between the second and fifth days; it is often transient or intermittent and is rarely of clinical significance unless the patient is taking anticoagulants, in which case a large hemorrhagic effusion may develop.
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The presence of right ventricular failure with raised venous pressure disproportionate to left, ventricular failure in the presence of an inferior myocardial infarction should make one consider right ventricular infarction. In the usual case of severe left ventricular failure followed by right ventricular failure, the former dominates. When the reverse is true, right ventricular infarction associated with enlargement and hypokinesis of the right ventricle may be present. The ventricular septum and the posterior left and right ventricles are usually infarcted.
3. Fever-Fever-is absent at the onset (in contrast to acute pericarditis) and during prolonged shock. It usually rises to 37.8-
C. Laboratory Findings: Leukocytosis of 10-20 thousand cells/mL usually develops on the second day and disappears in 1 week. The sedimentation rate is normal at onset, rises on the second or third day, and remains elevated for 1-3 weeks. SGOT activity increases in 6-12 hours, reaches a peak in 24—48 hours, and returns to normal in 3—5 days. Serum lactic acid dehydrogenase may remain elevated for 5-7 days. Serial determinations are helpful in equivocal instances. Creatine phosphokinase (CPK) isoenzyme activity may increase earliest (especially -the MB isoenzyme, derived almost exclusively from the myocardium), and, when determined every 2 hours, gives an estimate of the magnitude of the infarction, although for diagnosis, CPK determination every 6—12 hours is adequate.
D. Electrocardiography: Electrocardiographic changes do not correlate well with the clinical severity of the infarction. The characteristic pattern consists of specific changes that undergo a stereotyped “evolution ” over a matter of weeks in the average case. At the onset there are elevation of ST segment and T wave and abnormal Q waves; fee ST segment progressively returns to the baselines as T waves become symmetrically inverted. An unequivocal electrocardiographic diagnosis of infarction can only be made in the presence of all 3 abnormalities. Serial ST-T changes alone are compatible with but not diagnostic of infarction. The characteristic changes are not seen in the presence of left bundle branch block or when a previous infarct has permanently altered fee ECG. Even in these instances an ECG taken early in an attack often shows ST segment displacement. Hypertensive heart.wmv
Chest radiograph findings are usually normal in patients with angina pectoris. However, they may show cardiomegaly in patients with previous MI, ischemic cardiomyopathy, pericardial effusion, or acute pulmonary edema. Calcification of coronary arteries frequently correlates with major coronary artery disease.
These test results must be interpreted in the context of the likelihood of the presence of coronary artery disease determined from the patient’s history and physical examination findings. In a population with low prevalence, the predictive abilities of these tests are low; however, in patients with a high likelihood of coronary artery disease, the predictive value is much higher.
Stress echocardiography can be used to evaluate segmental wall motion during exercise. It detects changes in regional wall motion that occur during myocardial ischemia. Normal myocardium becomes hyperdynamic during exercise; ischemic segments become hypokinetic or akinetic.
Stress echocardiography has the advantage of simultaneous evaluation of LV function, cardiac dimensions, and valvular disease. It is especially useful in patients with baseline ECG abnormalities and those with systolic murmurs suggestive of aortic stenosis or hypertrophic cardiomyopathy.
It is also helpful for localizing ischemia and evaluating its severity.
Signs of severe coronary artery disease during exercise stress echocardiography include LV dilation, a decrease in global systolic function, and new or worsening mitral regurgitation. However, with dobutamine stress echocardiography, even in patients with severe coronary artery disease, the LV cavity may not dilate and global systolic function may improve.
A major problem with stress echocardiography is the technical difficulty with obtaining adequate images in some patients.
Thallium Tl 201 and technetium Tc 99m sestamibi are the most frequently used myocardial perfusion scintigraphy tests. These tests are especially useful in patients with baseline ECG abnormalities, to localize the region of ischemia, and as prognostic indicators. The presence of increased lung uptake upon thallium imaging is associated with a poor prognosis. Increased lung uptake, together with poststress dilation of the LV and multiple perfusion defects, is suggestive of either left main coronary artery disease or severe 3-vessel disease. The number of affected myocardial segments is predictive of long-term survival. Smaller perfusion defects are usually associated with peripheral coronary artery lesions, which are associated with a better prognosis. The absence of perfusion defects even in the presence of symptoms indicates an excellent prognosis.
Differential Diagnosis
In acute pericarditis, fever often precedes fee onset of pain, which may be predominantly pleuritic and is significantly relieved by breath-holding and leaning forward and made worse by swallowing. The friction rub appears earlier, is louder, is heard over a greater area, and is more persistent than in infarction, and a pleuropericardial rub is often present. There are no QRS changes, and ST elevation and T wave inversion are more widespread, without reciprocal changes (except in aVR). SGOT and LDH are rarely elevated.
Dissection of fee aorta causes violent chest pain feat is often of maximum severity at onset. It typically spreads up or down fee chest and back over a period of hours. Changes in pulses, changing aortic murmurs, and left pleural effusion or cardiac tamponade are distinctive features. Blood pressure does not fall early. Syncope or neurologic abnormalities are common. Electrocardiographic changes are not diagnostic of infarction unless fee coronary ostia arc involved in fee proximal dissection.
Acute pulmonary embolism may cause chest pain indistinguishable from myocardial infarction as well as hypotension, dyspnea, and distended neck veins, but fee ECG, regardless of coronarylike changes, will often show right axis deviation or right ventricular conduction defect early in fee course of fee acute process. SGOT and LDH are often elevated, as in myocardial infarction. The myocardial band isoenzyme of CPK is not elevated in acute pulmonary embolism. If the attack is not fatal, pulmonary infarction may follow, frequently causing pleuritic pain, hemoptysis, and localized lung findings. Thrombophlebitis is often found when careful examination is made of the legs, the groins, and the lower abdomen.
Cervical or thoracic spine disease produces sudden, severe chest pain similar to myocardial infarction; but orthopedic measures give relief and the ECG is normal.
Reflux esophagitis may simulate the pain of infarction, and the T waves may be flat or even inverted during the attack, but there is no hypotension or subsequent fever, leukocytosis, or increase in sedimentation rate, SGOT, LDH, or CPK.
Acute pancreatitis and acute cholecystitis may superficially mimic infarction by causing ST-T changes; Q wave abnormalities are rare. A past history of gastrointestinal symptoms, present findings in the abdomen, jaundice, elevated serum amylase, and x-ray findings differentiate these. Most helpful is the absence of diagnostic serial electrocardiographic changes and absence of elevated CPK-MB;
Spontaneous pneumothorax, mediastinal emphysema, preemptive herpes zoster, and severe psychophysiologic cardiovascular reactions may have to be differentiated from myocardial infarction.
Complications
Congestive heart failure and shock may be present at onset of infarction or may develop insidiously or abruptly following an arrhythmia or pulmonary embolization. Sedation and weakness may mask the presence of dyspnea and orthopnea. Distension of neck veins, persistent basal rales, gallop rhythm, the appearance of the murmur of mitral insufficiency, abnormal cardiac pulsations, an enlarging tender liver, and peripheral edema should besought daily. If increasing cardiac failure or evidence of poor cardiac output develops, a Swan-Ganz flow-directed balloon catheter should be inserted to determine precisely the hemodynamic abnormalities and to assist in treatment. Portable chest x-ray films to recognize pulmonary venous congestion are desirable. If anticoagulants are not given, pulmonary embolism secondary to phlebitis of the leg or pelvic veins occurs in 5-10% of patients during the acute and convalescent stage.
Arrhythmias occur commonly after myocardial infarction and are thought to be the cause of death in about 40% of patients. The mechanism is either cardiac arrest or ventricular fibrillation; the former occurs following shock or heart failure, and the latter is more apt to be a primary event (although it can be secondary). Continuous monitoring has revealed a higher incidence of ventricular tachycardia, complete atrioventricular block, and other less serious arrhythmias than was formerly suspected. The appearance of left anterior hemiblock, especially combined with right bundle branch block, often precedes the development of complete atrioventricular block and requires insertion of a prophylactic pacemaker. Ventricular premature beats often precede more serious arrhythmias in late or secondary but may not in early or primary ventricular fibrillation. Atrial arrhythmias are less common and often transient, as is the case with atrial fibrillation. The prompt recognition of arrhythmias is essential in order to initiate treatment.
Cerebrovascular accident may result from a fall in blood pressure associated with myocardial infarction or from embolism secondary to a mural thrombus. It is advisable to take an ECG in all patients with “cerebrovascular accident.“
Recurrent myocardial infarction or extension of the infarction occurs in about 5% of patients during recovery from the initial attack.
Rupture of the heart is uncommon. When it occurs, it is usually in the first week.
Perforation of the ventricular septum is rare, characterized by the sudden appearance of a loud, harsh systolic murmur and thrill over the lower left parastemal area or apex and acute heart failure. This must be distinguished from mitral insufficiency caused by papillary muscle infarction or dysfunction. The diagnosis may sometimes be made by passing (at the bedside) a pulmonary artery flow-directed catheter and noting the size of the v wave in the wedged position and the oxygen content in the right ventricle. Two-dimensional echocardiography may demonstrate the perforation of the ventricular septum and so obviate the need for catheterization. Both lesions may precipitate cardiac failure and require cardiac surgery when the patient’s condition has stabilized in weeks or months and right and left heart catheterization reveals a significant hemodynamic lesion. ‘Emergency surgical repair is sometimes required but has a high mortality rate. An effort should be made to delay surgery for at least a month.
Ventricular aneurysm and peripheral arterial embolism may occur early or not for months after recovery. The spectrum of ventricular aneurysm is now recognized to extend from frank outpocketing of an area of myocardium with well-demarcated paradoxic pulsations to localized poor contraction or irregular pulsation seen on cineangiography. Approximately 20% or patients develop some form of aneurysm or left ventricular hypokinesis, recognized clinically by abnormal paradoxic precordial pulsations and proved by gated pool scintigraphy, 2-dimensional echocardiography, cinefluoroscopy, or left ventricular cineangiography. Some of these patients develop refractory cardiac failure and benefit from surgical excision.
The shoulder-hand syndrome is a rare preventable disorder caused by prolonged immobilization of the arms and shoulders, possibly due to “reflex sympathetic dystrophy.” Early pain and tenderness over the affected shoulder are followed by pain and swelling and weakness of the hand, with excessive or deficient sweating. Oliguria, anuria, or, rarely, tubular necrosis may result if shock persists.
TREATMENT
Medical Care: The main goals of treatment in angina pectoris are to relieve the symptoms, slow the progression of disease, and reduce the possibility of future events, especially MI and premature death.
General measures
Smoking cessation results in a significant reduction of acute adverse effects on the heart and may reverse, or at least slow, atherosclerosis. Strongly encourage patients to quit smoking, and take an active role in helping them to achieve this goal.
Treat risk factors, including hypertension, diabetes mellitus, obesity, and hyperlipidemia.
Several clinical trials have shown that in patients with established coronary artery disease, reduction of low-density lipoprotein (LDL) level with a beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor (ie, statin) is associated with significant reductions in both mortality rate and major cardiac events.
These benefits are present even in patients with mild-to-moderate elevations of LDL cholesterol level.
Recent trials with cholesterol-lowering agents have confirmed the benefits of the therapeutic LDL lowering in older persons.
Angiographic studies demonstrate that a reduction of the LDL level in patients with coronary artery disease could cause slowing of progression, stabilization, or even regression of coronary artery lesions.
A recent study demonstrates a significant reduction of symptomatic myocardial ischemia in patients with unstable angina or non–Q-wave infarction with the administration of a statin during the early acute phase.
In a more recent study of 10,001 patients with stable coronary artery disease, an aggressive cholesterol-lowering approach with atorvastatin 80 mg daily (mean cholesterol level of 77 mg/dL) compared to a less-aggressive approach with atorvastatin 10 mg daily (mean cholesterol level of 101 mg/dL) resulted in a 2.2% absolute reduction and a 22% relative reduction in the occurrence of a first major cardiovascular event (defined as death from coronary heart disease; nonfatal, non–procedure-related myocardial infarction; resuscitation from cardiac arrest; or fatal or nonfatal stroke).This occurred with a greater incidence of elevated aminotransferase levels with the aggressive cholesterol-lowering approach (1.2% vs 0.2%, p<0.001).
On the basis of several recent studies that have demonstrated the benefits of more aggressive LDL-lowering therapies in high-risk patients with coronary artery disease, the Committee of the National Cholesterol Education Program recently made the following modifications to the Adult Treatment Panel III (ATP III) guidelines.
In high-risk patients, a serum LDL cholesterol level of less than 100 mg/dL is the goal.
In very high-risk patients, an LDL cholesterol level goal of less than 70 mg/dL is a therapeutic option. Patients in the category of very high risk are those with established coronary artery disease with one of the following: multiple major risk factors (especially diabetes), severe and poorly controlled risk factors (especially continued cigarette smoking), multiple risk factors of the metabolic syndrome (especially high triglyceride levels [>200 mg/dL] plus non-HDL cholesterol level [>130 mg/dL] with low HDL cholesterol level [<40 mg/dL]), and patients with acute coronary syndromes.
For moderately high-risk persons (2+ risk factors), the recommended LDL cholesterol level is less than130 mg/dL, but an LDL cholesterol level of 100 mg/dL is a therapeutic option.
Some triglyceride-rich lipoproteins, including partially degraded very LDL levels, are believed to be independent risk factors for coronary artery disease. In daily practice, non-HDL cholesterol level (ie, LDL + very LDL cholesterol [total cholesterol – HDL cholesterol]) is the most readily available measure of the total pool of these atherogenic lipoproteins. Thus, the ATP III has identified non-HDL cholesterol level as a secondary target of therapy in persons with high triglyceride levels (>200 mg/dL). The goal for non-HDL cholesterol level (for persons with serum triglyceride levels >200 mg/dL) is 30 mg/dL higher than the identified LDL cholesterol level goal.
Patients with established coronary disease and low HDL cholesterol levels are at high risk for recurrent events and should be targeted for aggressive nonpharmacological (ie, dietary modification, weight loss, physical exercise) and pharmacological treatment.
A recent study demonstrated that in patients with established coronary artery disease who have low HDL and low-risk LDL levels, drug therapy with medications that raise HDL cholesterol levels and lower triglyceride levels but have no effect on LDL cholesterol levels (eg, gemfibrozil) could significantly reduce the risk of major cardiac events.
Currently, the accepted approach to the management of patients with coronary artery disease and low HDL levels is as follows:
In all persons with low HDL cholesterol levels, the primary target of therapy is to achieve the ATP III guideline LDL cholesterol level goals with diet, exercise, and drug therapy as needed.
After reaching the targeted LDL level goal, emphasis shifts to other issues. That is, in patients with low HDL cholesterol levels who have associated high triglyceride levels (>200 mg/dL), the secondary priority is to achieve the non-HDL cholesterol level goal of 30 mg/dL higher than the identified LDL cholesterol level goal. In patients with isolated low HDL cholesterol levels (triglycerides <200 mg/dL), drugs to raise the HDL cholesterol level (eg, gemfibrozil, nicotinic acid) can be considered.
Exercise training results in improvement of symptoms, increase in the threshold of ischemia, and improvement of patients’ sense of well-being. However, before enrolling a patient in an exercise-training program, perform an exercise tolerance test to establish the safety of such a program.
Consider enteric-coated aspirin at a dose of 80-325 mg/d for all patients with stable angina who have no contraindications to its use. In patients in whom aspirin cannot be used because of allergy or gastrointestinal complications, consider clopidogrel.
Although early observational studies suggested a cardiovascular protective effect with the use of hormone replacement therapy, recent large randomized trials failed to demonstrate any benefit with hormone replacement therapy in the primary or secondary prevention of cardiovascular disease.
In fact, these studies even demonstrated an increased risk of coronary artery disease and stroke in patients on hormone replacement therapy.
The Women’s Health Initiative study demonstrated that the use of hormone replacement therapy for 1 year in 10,000 healthy postmenopausal women is associated with 7 more instances of coronary artery disease, 8 more strokes, 8 more pulmonary emboli, 8 more invasive breast cancers, 5 fewer hip fractures, and 6 fewer colorectal cancers.
Based on these data, the risks and benefits of hormone replacement therapy must be assessed on an individual basis for each patient.
Sublingual nitroglycerin has been the mainstay of treatment for angina pectoris. Sublingual nitroglycerin can be used for acute relief of angina and prophylactically before activities that may precipitate angina. No evidence indicates that long-acting nitrates improve survival in patients with coronary artery disease.
Beta-blockers are also used for symptomatic relief of angina and prevention of ischemic events. They work by reducing myocardial oxygen demand and by decreasing the heart rate and myocardial contractility. Beta-blockers have been shown to reduce the rates of mortality and morbidity following acute MI.
Long-acting heart rate–slowing calcium channel blockers can be used to control anginal symptoms in patients with a contraindication to beta-blockers and in those in whom symptomatic relief of angina cannot be achieved with the use of beta-blockers, nitrates, or both. Avoid short-acting dihydropyridine calcium channel blockers because they have been shown to increase the risk of adverse cardiac events.
Anginal symptoms in patients with Prinzmetal angina can be treated with calcium channel blockers with or without nitrates. In one study, supplemental vitamin E added to a calcium channel blocker significantly reduced anginal symptoms among such patients.
In patients with syndrome X and hypertension, ACE inhibitors may normalize thallium perfusion defects and increase exercise capacity.
MEDICATION
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Drug Category: Antiplatelet agents — Prevent thrombus formation by inhibiting platelet aggregation. Aspirin is proven beneficial in primary and secondary prevention of coronary artery disease. In patients with aspirin intolerance, use clopidogrel. Clopidogrel is also used in combination with aspirin after coronary stent placement. Recently, clopidogrel use in addition to aspirin has been shown to be significantly superior to aspirin alone in patients with acute coronary syndrome without ST-segment elevation MI.
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Drug Name |
Aspirin (Bayer, Empirin, Anacin) — Prevents platelet aggregation by irreversible cyclooxygenase inhibition with subsequent suppression of thromboxane A2. Antiplatelet effect can last as long as 7 d. |
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Adult Dose |
81-325 mg PO qd |
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Pediatric Dose |
Not established |
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Contraindications |
Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma |
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Interactions |
Antacids and urinary alkalinizers may decrease effects; corticosteroids decrease salicylate serum levels; anticoagulants may cause additive hypoprothrombinemic effects and increased bleeding time; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs |
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Pregnancy |
D – Unsafe in pregnancy |
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Precautions |
May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in patients with severe anemia, history of blood coagulation defects, or taking anticoagulants; adverse effects include prolonged bleeding time, rhinitis, asthma, urticaria, and exacerbation of gout; monitor BP, BUN, and uric acid level; consider discontinuing 7 d before surgery |
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Drug Name |
Clopidogrel (Plavix) — Selectively inhibits ADP binding to platelet receptor and subsequent ADP-mediated activation of GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Consider in patients with contraindication to aspirin. |
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Adult Dose |
75 mg PO qd |
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Pediatric Dose |
Not established |
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Contraindications |
Documented hypersensitivity; active pathological bleeding |
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Interactions |
Naproxen associated with increased occult GI blood loss; prolongs bleeding time; safety of coadministration with warfariot established |
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Pregnancy |
C – Safety for use during pregnancy has not been established. |
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Precautions |
Caution in patients at increased risk of bleeding from trauma, surgery, or other pathological conditions; caution in patients with lesions with propensity to bleed (eg, ulcers); adverse effects include rash, diarrhea, purpura, GI ulcers, neutropenia, and rare cases of agranulocytosis; consider discontinuing 7 d before surgery |
Drug Category: Beta-adrenergic blocking agents — Work by competing with endogenous catecholamines for beta-adrenergic receptors. Reduce myocardial oxygen consumption via several effects, including decrease in resting and exercise heart rates and reductions in myocardial contractility and afterload. Classified as nonselective, beta-1 selective, and having intrinsic sympathomimetic effects.
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Drug Name |
Metoprolol (Lopressor, Toprol XL) — Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. Is lipophilic and penetrates CNS. |
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Adult Dose |
50-200 mg PO bid |
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Pediatric Dose |
Not established |
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Contraindications |
Documented hypersensitivity; uncompensated CHF; bradycardia; asthma; cardiogenic shock; AV conduction abnormalities |
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Interactions |
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; sparfloxacin, phenothiazines, astemizole, calcium channel blockers, quinidine, flecainide, and contraceptives may increase toxicity; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine |
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Pregnancy |
B – Usually safe but benefits must outweigh the risks. |
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Precautions |
Beta-adrenergic blockade may mask signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor BP, heart rate, and ECG; adverse effects include hypotension, decreased libido, impotence, lethargy, depression, and decreased HDL; may cause less bronchial tree and arterial smooth muscle constriction |
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Drug Name |
Atenolol (Tenormin) — Selectively blocks beta-1 receptors with little or no effect on beta-2 receptors. Is hydrophilic and does not penetrate CNS. |
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Adult Dose |
50-200 mg PO qd |
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Pediatric Dose |
Not established |
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Contraindications |
Documented hypersensitivity; CHF; pulmonary edema; cardiogenic shock; AV conduction abnormalities; heart block (without pacemaker) |
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Interactions |
Aluminum salts, barbiturates, calcium salts, cholestyramine, NSAIDs, penicillins, and rifampin may decrease effects; haloperidol, hydralazine, loop diuretics, and MAOIs may increase toxicity |
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Pregnancy |
C – Safety for use during pregnancy has not been established. |
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Precautions |
Beta-adrenergic blockade may hide symptoms of acute hypoglycemia and mask signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism and cause thyroid storm; monitor patients closely and withdraw drug slowly; adverse effects include bradycardia, hypotension, decreased libido, impotence, and decreased HDL; beta1-selective blockers may cause less bronchial tree and arterial smooth muscle constriction; titrate dose carefully to level of patient tolerance and effectiveness |
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Drug Name |
Propranolol (Inderal) — Nonselective beta-blocker that is lipophilic (penetrates CNS). Although generally short-acting agent, long-acting preparations also available. |
|
Adult Dose |
IR: 40-160 mg PO bid |
|
Pediatric Dose |
Not established |
|
Contraindications |
Documented hypersensitivity; history of bronchospasm; uncompensated CHF; bradycardia; cardiogenic shock; AV conduction abnormalities |
|
Interactions |
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; may increase toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines |
|
Pregnancy |
C – Safety for use during pregnancy has not been established. |
|
Precautions |
Beta-adrenergic blockade may mask signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely; adverse effects include bronchial constriction, Raynaud phenomenon, hypotension, decreased libido, impotence, lethargy, depression, and decreased HDL; caution in Wolff-Parkinson-White syndrome and renal or hepatic dysfunction |
Drug Category: Calcium channel blockers — Reduce transmembrane flux of calcium via calcium channels. Cause smooth muscle relaxation, resulting in peripheral arterial vasodilation and afterload reduction. Indicated when symptoms persist despite treatment with beta-blockers or when beta-blockers are contraindicated. Also indicated in patients with Prinzmetal angina with or without nitrates.
|
Drug Name |
Amlodipine (Norvasc) — During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. |
|
Adult Dose |
5-10 mg PO qd |
|
Pediatric Dose |
Not established |
|
Contraindications |
Documented hypersensitivity; severe CHF; sick sinus syndrome; second- or third-degree AV block; hypotension (< |
|
Interactions |
Fentanyl may increase hypotensive effects; may increase cyclosporine levels; H2 blockers (eg, cimetidine) may increase toxic effects |
|
Pregnancy |
C – Safety for use during pregnancy has not been established. |
|
Precautions |
Severe aortic stenosis, CHF, hepatic dysfunction; adverse effects include headache, edema, flushing, palpitation, drowsiness, and fatigue |
|
Drug Name |
Diltiazem (Cardizem CD, Dilacor) — During depolarization, inhibits calcium ions from entering slow channels and voltage-sensitive areas of vascular smooth muscle and myocardium. |
|
Adult Dose |
IR: 120-360 mg PO divided tid/qid |
|
Pediatric Dose |
Not established |
|
Contraindications |
Documented hypersensitivity; severe CHF; sick sinus syndrome; second- or third-degree AV block; hypotension (< |
|
Interactions |
May increase carbamazepine, digoxin, cyclosporine, and theophylline levels; when administered with amiodarone, may cause bradycardia and decrease in cardiac output; when given with beta-blockers may increase cardiac depression; cimetidine may increase levels |
|
Pregnancy |
C – Safety for use during pregnancy has not been established. |
|
Precautions |
Caution in impaired renal or hepatic function; may increase LFT levels, and hepatic injury may occur; adverse effects include constipation, AV conduction block, worsening of heart failure, peripheral edema, bradycardia, and AV dissociation |
|
Drug Name |
Verapamil (Calan, Covera) — During depolarization, inhibits calcium ion from entering slow channels or voltage-sensitive areas of vascular smooth muscle and myocardium. |
|
Adult Dose |
IR: 80-120 mg PO tid/qid |
|
Pediatric Dose |
Not established |
|
Contraindications |
Documented hypersensitivity; severe CHF; sick sinus syndrome; second- or third-degree AV block; hypotension (< |
|
Interactions |
May increase carbamazepine, digoxin, theophylline, and cyclosporine levels; amiodarone can cause bradycardia and decrease in cardiac output; when administered concurrently with beta-blockers may increase cardiac depression; cimetidine may increase levels |
|
Pregnancy |
C – Safety for use during pregnancy has not been established. |
|
Precautions |
Hepatocellular injury may occur; transient elevations of transaminases with and without concomitant elevations in alkaline phosphatase and bilirubin have occurred (elevations have been transient and may disappear with continued treatment); monitor liver function periodically; adverse effects include constipation, AV dissociation, worsening heart failure, bradycardia, negative inotropism, and hypotension |
Drug Category: Short-acting nitroglycerins — Suitable for immediate relief of exertional or rest angina. Can also be used for prophylaxis several minutes before planned exercise to avoid angina. Reduce myocardial oxygen demand by reduction of LV and arterial pressure, primarily by reducing preload.
|
Drug Name |
Nitroglycerin (Nitrostat, Nitro-bid, Nitrol) — Causes relaxation of vascular smooth muscle by stimulating intracellular cyclic GMP production. Result is decrease in BP. |
|
Adult Dose |
0.3-0.6 mg SL prn |
|
Pediatric Dose |
Not established |
|
Contraindications |
Documented hypersensitivity; severe anemia; shock; postural hypotension; head trauma; closed-angle glaucoma; cerebral hemorrhage; hypertrophic obstructive cardiomyopathy |
|
Interactions |
Concurrent sildenafil (Viagra) may cause severe hypotension and death; aspirin may increase serum concentrations; calcium channel blockers may cause markedly symptomatic orthostatic hypotension (dose adjustment of either agent may be necessary) |
|
Pregnancy |
C – Safety for use during pregnancy has not been established. |
|
Precautions |
Caution in coronary artery disease and low systolic BP; adverse effects include hypotension, flushing, headache, light-headedness, and tolerance (8- to 12-h nitrate-free interval is most effective method to prevent development of tolerance); high IV doses may cause methemoglobinemia, heparin resistance, and ethanol intoxication; ischemia may worsen upon withdrawal |
Drug Category: Long-acting nitroglycerins — Reduce LV preload and afterload by venous and arterial dilation, which subsequently reduces myocardial oxygen consumption and relieves angina. Also cause dilation of epicardial coronary arteries, which is beneficial in patients with coronary spasm. In addition, nitroglycerin has antithrombotic and antiplatelet effects in patients with angina pectoris. No evidence suggests that nitrates improve survival or slow progression of coronary artery disease.
|
Drug Name |
Isosorbide (Isordil, ISMO) — Relaxes vascular smooth muscle by stimulating intracellular cyclic GMP. Decreases LV pressure (ie, preload) and arterial resistance (ie, afterload). Reduces cardiac oxygen demand by decreasing LV pressure and dilating arteries. |
|
Adult Dose |
Isosorbide dinitrate: 2.5-10 mg SL prn IR 10-30 mg PO bid/tid SR 80-120 mg PO qd IR Isosorbide mononitrate: 10-20 mg PO bid SR 30-120 mg PO qd |
|
Pediatric Dose |
Not established |
|
Contraindications |
Documented hypersensitivity; severe anemia; closed-angle glaucoma; postural hypotension; head trauma; cerebral hemorrhage |
|
Interactions |
Alcohol may cause severe hypotension and cardiovascular collapse; aspirin may increase serum concentrations and actions; calcium channel blockers may increase symptomatic orthostatic hypotension (adjust dose of either agent); may decrease effects of heparin |
|
Pregnancy |
C – Safety for use during pregnancy has not been established. |
|
Precautions |
Tolerance to vascular and antianginal effects of nitrates may develop; minimize tolerance by using smallest effective dose or pulse therapy (intermittent dosing) or by alternating with other coronary vasodilators (take last daily dose of short-acting agent no later than 7 pm); caution when administering to patients with glaucoma |
Drug Category: Angiotensin-converting enzyme inhibitors — Recently shown to reduce rates of death, MI, stroke, and need for revascularization procedures in patients with coronary artery disease or diabetes mellitus and at least one other cardiovascular risk factor, irrespective of the presence of hypertension or heart failure.
|
Drug Name |
Ramipril (Altace) — Prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone secretion. |
|
Adult Dose |
2.5-5 mg PO qd; not to exceed 20 mg/d |
|
Pediatric Dose |
Not established |
|
Contraindications |
Documented hypersensitivity; history of angioedema |
|
Interactions |
May increase digoxin, lithium, and allopurinol levels; probenecid may increase levels; coadministration with diuretics increases hypotensive effects; NSAIDs may reduce hypotensive effects |
|
Pregnancy |
C – Safety for use during pregnancy has not been established. |
|
Precautions |
Category D in second and third trimesters of pregnancy; adverse effects include persistent cough, angioedema, hypotension, and prerenal azotemia; caution in renal impairment, valvular stenosis, or severe CHF |
Drug Category: Anti-ischemic agents, miscellaneous — Ranolazine elicits action unlike beta-blockers, calcium antagonists, or nitrates. It does not affect hemodynamics or contractile and conduction parameters.
|
Drug Name |
Ranolazine (Ranexa) — Cardioselective anti-ischemic agent (piperazine derivative) that partially inhibits fatty acid oxidation. Also inhibits late sodium current into myocardial cells and prolongs QTc interval. Indicated for chronic angina unresponsive to other antianginal treatments. Used in combination with amlodipine, beta-blockers, or nitrates. Unlike beta-blockers, calcium channel blockers, and nitrates, does not reduce blood pressure or heart rate. Effect on angina rate or exercise tolerance appears to be smaller in women than in men. Absorption is highly variable but unaffected by food. |
|
Adult Dose |
500 mg PO bid initially; if necessary, may increase to 1000 mg PO bid |
|
Pediatric Dose |
Not established |
|
Contraindications |
Documented hypersensitivity; preexisting QT prolongation; hepatic impairment (Child-Pugh class A [mild], B [moderate], or C [severe]); QT-prolonging drugs (see Interactions); potent or moderate CYP4503A inhibitors (eg, ketoconazole, diltiazem) |
|
Interactions |
CYP4503A and P-gp substrate; potent CYP3A inhibitors (eg, ketoconazole at 200 mg bid) increase levels approximately 3.2-fold, moderate CYP3A inhibitors (eg, diltiazem at 180-360 mg/d) increase levels approximately 1.8- to 2.3-fold, and verapamil (a CYP3A and P-gp inhibitor) increases levels approximately 2-fold; caution with other P-gp inhibitors (eg, ritonavir, cyclosporine); toxicity may occur when coadministered with other drugs that increase QTc interval (eg, class I and III antiarrhythmic agents, certain macrolide and quinolone antibiotics, phenothiazines, TCAs) |
|
Pregnancy |
C – Safety for use during pregnancy has not been established. |
|
Precautions |
Causes dose-related QTc-interval prolongation (obtain baseline and follow-up ECGs to monitor for torsades de pointes and potential for sudden death; mild and moderate hepatic impairment increases QTc interval compared with normal hepatic function at same plasma level; increases blood pressure by approximately |
FOLLOW-UP
Deterrence/Prevention:
Coronary atherosclerosis is the main preventable cause of mortality in the United States. A rigorous effort to address correctable risk factors is the mainstay of preventive cardiovascular medicine.
Smoking cessation is the single most effective preventive intervention to reduce coronary atherosclerosis prevalence. It has been associated with a coronary artery disease reduction of 7-47% in primary prevention settings.
Aggressive treatment of diabetes mellitus, hypertension, LV hypertrophy, hyperlipidemia, and obesity has an important role in the prevention of coronary artery disease.
The most important recent development in coronary atherosclerosis risk modification is the introduction of inhibitors of beta-hydroxy-beta-methylglutaryl coenzyme A reductase. Reductions of total and LDL cholesterol levels by 25% and 35%, respectively, can achieve a similar reduction in rates of total and coronary mortality, MI, and need for coronary revascularization.
Complications:
Complications of angina pectoris include unstable angina, MI, and death.
Prognosis:
Important prognostic indicators in patients with angina pectoris include LV function, severity and location of atherosclerotic lesions, and response of symptoms to medical treatment.
LV function is the strongest predictor of long-term survival. Elevated LV end-diastolic pressure and volume along with reduced LV ejection fraction (<40%) are poor prognostic signs.
Critical lesions of left main and proximal left anterior descending coronary arteries are associated with a greater risk. Mortality rates are also directly associated with the number of epicardial arteries involved.
Unstable angina, recent MI, or both is a sign of atherosclerotic plaque instability, which is a strong predictor of increased risk of short-term coronary events.
A number of signs during noninvasive testing are predictive of a higher risk of coronary events, including ST-segment depression of more than
Patients who continue to smoke after an MI have a 22-47% increased risk of reinfarction and death.
In general, Prinzmetal angina and syndrome X are associated with excellent long-term prognoses.
Patient Education:
Educating patients about the benefits of smoking cessation, a low-cholesterol diet, physical activity, and periodic screening for diabetes mellitus and hypertension is the prime component of a long-term management plan.
TABLE AHA/ACC Secondary Prevention for Patients With Coronary and Other Vascular Disease: 2006 Update
|
|
Intervention Recommendations With Class of Recommendation and Level of Evidence |
|
SMOKING: |
•Ask about tobacco use status at every visit. I (B)•Advise every tobacco user to quit. I (B)•Assess the tobacco user’s willingness to quit. I (B)•Assist by counseling and developing a plan for quitting. I (B)•Arrange follow-up, referral to special programs, or pharmacotherapy (including nicotine replacement and bupropion). I (B)•Urge avoidance of exposure to environmental tobacco smoke at work and home. I (B) |
|
Goal |
|
|
Complete cessation. No exposure to environmental tobacco smoke. |
|
|
BLOOD PRESSURE CONTROL: |
For all patients: |
|
Goal |
•Initiate or maintain lifestyle modification—weight control; increased physical activity; alcohol moderation; sodium reduction; and emphasis on increased consumption of fresh fruits, vegetables, and low-fat dairy products. I (B) |
|
<140/90 mm Hg |
|
|
or |
|
|
<130/80 mm Hg if patient has diabetes or chronic kidney disease |
|
|
|
For patients with blood pressure ≥140/90 mm Hg (or ≥130/80 mm Hg for individuals with chronic kidney disease or diabetes):•As tolerated, add blood pressure medication, treating initially with β-blockers and/or ACE inhibitors, with addition of other drugs such as thiazides as needed to achieve goal blood pressure. I (A) |
|
|
[For compelling indications for individual drug classes in specific vascular diseases, see Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7).]4 |
|
LIPID MANAGEMENT: |
For all patients:•Start dietary therapy. Reduce intake of saturated fats (to <7% of total calories), trans-fatty acids, and cholesterol (to <200 mg/d). I (B)•Adding plant stanol/sterols (2 g/d) and viscous fiber (>10 g/d) will further lower LDL-C.•Promote daily physical activity and weight management. I (B)•Encourage increased consumption of omega-3 fatty acids in the form of fish or in capsule form (1 g/d) for risk reduction. For treatment of elevated triglycerides, higher doses are usually necessary for risk reduction. IIb (B) |
|
Goal |
|
|
LDL-C <100 mg/dL |
|
|
If triglycerides are ≥200 mg/dL, non-HDL-C should be <130 mg/dL |
|
|
|
For lipid management: |
|
|
Assess fasting lipid profile in all patients, and within 24 hours of hospitalization for those with an acute cardiovascular or coronary event. For hospitalized patients, initiate lipid-lowering medication as recommended below before discharge according to the following schedule: •LDL-C should be <100 mg/dL I (A), and•Further reduction of LDL-C to <70 mg/dL is reasonable. IIa (A)•If baseline LDL-C is ≥100 mg/dL, initiate LDL-lowering drug therapy.I (A)•If on-treatment LDL-C is ≥100 mg/dL, intensify LDL-lowering drug therapy (may require LDL-lowering drug combination. I (A)•If baseline LDL-C is 70 to 100 mg/dL, it is reasonable to treat to LDL-C <70 mg/dL. IIa (B)•If triglycerides are 200 to 499 mg/dL, non-HDL-C should be <130 mg/dL. I (B), and•Further reduction of non-HDL-C to <100 mg/dL is reasonable. IIa (B)•Therapeutic options to reduce non-HDL-C are: ⇒More intense LDL-C–lowering therapy I (B), or⇒Niacin (after LDL-C–lowering therapy) IIa (B), or⇒Fibrate therapy# (after LDL-C–lowering therapy) IIa (B)•If triglycerides are ≥500 mg/dL, therapeutic options to prevent pancreatitis are fibrate or niacin before LDL-lowering therapy; and treat LDL-C to goal after triglyceride-lowering therapy. Achieve non-HDL-C <130 mg/dL if possible. I (C) |
|
PHYSICAL ACTIVITY: |
•For all patients, assess risk with a physical activity history and/or an exercise test, to guide prescription. I (B)•For all patients, encourage 30 to 60 minutes of moderate-intensity aerobic activity, such as brisk walking, on most, preferably all, days of the week, supplemented by an increase in daily lifestyle activities (eg, walking breaks at work, gardening, household work). I (B)•Encourage resistance training 2 days per week. IIb (C)•Advise medically supervised programs for high-risk patients (eg, recent acute coronary syndrome or revascularization, heart failure). I (B) |
|
Goal |
|
|
30 minutes, 7 days per week (minimum 5 days per week) |
|
|
WEIGHT MANAGEMENT: |
•Assess body mass index and/or waist circumference on each visit and consistently encourage weight maintenance/reduction through an appropriate balance of physical activity, caloric intake, and formal behavioral programs when indicated to maintain/achieve a body mass index between 18.5 and 24.9 kg/m2. I (B)•If waist circumference (measured horizontally at the iliac crest) is ≥35 inches in women and ≥40 inches in men, initiate lifestyle changes and consider treatment strategies for metabolic syndrome as indicated. I (B)•The initial goal of weight loss therapy should be to reduce body weight by approximately 10% from baseline. With success, further weight loss can be attempted if indicated through further assessment. I (B) |
|
Goal |
|
|
Body mass index: 18.5 to 24.9 kg/m2 |
|
|
Waist circumference: men <40 inches, women <35 inches |
|
|
DIABETES MANAGEMENT: |
•Initiate lifestyle and pharmacotherapy to achieve near-normal HbA1c. I (B)•Begin vigorous modification of other risk factors (eg, physical activity, weight management, blood pressure control, and cholesterol management as recommended above). I (B)•Coordinate diabetic care with patient’s primary care physician or endocrinologist. I (C) |
|
Goal |
|
|
HbA1c <7% |
|
|
ANTIPLATELET AGENTS/ ANTICOAGULANTS: |
•Start aspirin 75 to 162 mg/d and continue indefinitely in all patients unless contraindicated. I (A)⇒For patients undergoing coronary artery bypass grafting, aspirin should be started within 48 hours after surgery to reduce saphenous vein graft closure. Dosing regimens ranging from 100 to 325 mg/d appear to be efficacious. Doses higher than 162 mg/d can be continued for up to 1 year. I (B)•Start and continue clopidogrel 75 mg/d in combination with aspirin for up to 12 months in patients after acute coronary syndrome or percutaneous coronary intervention with stent placement (≥1 month for bare metal stent, ≥3 months for sirolimus-eluting stent, and ≥6 months for paclitaxel-eluting stent). I (B)⇒Patients who have undergone percutaneous coronary intervention with stent placement should initially receive higher-dose aspirin at 325 mg/d for 1 month for bare metal stent, 3 months for sirolimus-eluting stent, and 6 months for paclitaxel-eluting stent. I (B)•Manage warfarin to international normalized ratio=2.0 to 3.0 for paroxysmal or chronic atrial fibrillation or flutter, and in post–myocardial infarction patients when clinically indicated (eg, atrial fibrillation, left ventricular thrombus). I (A)•Use of warfarin in conjunction with aspirin and/or clopidogrel is associated with increased risk of bleeding and should be monitored closely. I (B) |
|
RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM BLOCKERS: |
ACE inhibitors:•Start and continue indefinitely in all patients with left ventricular ejection fraction ≤40% and in those with hypertension, diabetes, or chronic kidney disease, unless contraindicated. I (A)•Consider for all other patients. I (B)•Among lower-risk patients with normal left ventricular ejection fraction in whom cardiovascular risk factors are well controlled and revascularization has been performed, use of ACE inhibitors may be considered optional. IIa (B) |
|
|
Angiotensin receptor blockers:•Use in patients who are intolerant of ACE inhibitors and have heart failure or have had a myocardial infarction with left ventricular ejection fraction ≤40%. I (A)•Consider in other patients who are ACE inhibitor intolerant. I (B)•Consider use in combination with ACE inhibitors in systolic-dysfunction heart failure. IIb (B) |
|
|
Aldosterone blockade:•Use in post–myocardial infarction patients, without significant renal dysfunction or hyperkalemia, who are already receiving therapeutic doses of an ACE inhibitor and β-blocker, have a left ventricular ejection fraction ≤40%, and have either diabetes or heart failure. I (A) |
|
β-BLOCKERS: |
•Start and continue indefinitely in all patients who have had myocardial infarction, acute coronary syndrome, or left ventricular dysfunction with or without heart failure symptoms, unless contraindicated. I (A) |
|
|
Consider chronic therapy for all other patients with coronary or other vascular disease or diabetes unless contraindicated. IIa (C) |
|
INFLUENZA VACCINATION: |
Patients with cardiovascular disease should have an influenza vaccination. I (B) |
TABLE 2Classification of Recommendations and Level of Evidence
|
Classification of Recommendations |
|
Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is beneficial, useful, and effective. |
|
Class II: Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment. |
|
Class IIa: Weight of evidence/opinion is in favor of usefulness/efficacy. |
|
Class IIb: Usefulness/efficacy is less well established by evidence/opinion. |
|
Class III: Conditions for which there is evidence and/or general agreement that a procedure/treatment is not useful/effective and in some cases may be harmful. |
|
Level of Evidence |
|
Level of Evidence A: Data derived from multiple randomized clinical trials or meta-analyses. |
|
Level of Evidence B: Data derived from a single randomized trial or nonrandomized studies. |
|
Level of Evidence C: Only consensus opinion of experts, case studies, or standard-of-care. |
Trials involving other secondary prevention therapies also have influenced major practice guidelines used to formulate the recommendations in this update. Thus, specific recommendations for clopidogrel use in post–acute coronary syndrome or post–percutaneous coronary intervention–stented patients are now included in this 2006 update. The present update also recommends lower-dose aspirin for chronic therapy. The results of additional studies have further confirmed the benefit of aldosterone antagonist therapy among patients with impaired left ventricular function. Finally, recently published findings of a trial involving angiotensin-converting enzyme inhibitor therapy among patients at relatively low risk with stable coronary disease and normal left ventricular function influenced the recommendations.
The writing group has for the first time added a recommendation with regard to influenza vaccination. According to the US Centers for Disease Control and Prevention, vaccination with inactivated influenza vaccine is recommended for individuals who have chronic disorders of the cardiovascular system because they are at increased risk for complications from influenza.
The writing group emphasizes the importance of giving consideration to the use of cardiovascular medications that have been proved in randomized clinical trials to be of benefit. This strengthens the evidence-based foundation for therapeutic application of these guidelines. The committee acknowledges that ethnic minorities, women, and the elderly are underrepresented in many trials and urges physician and patient participation in trials that will provide additional evidence with regard to therapeutic strategies for these groups of patients.
In the 11 years since the guidelines were first published, 2 other developments have made them even more important in clinical care. First, the aging of the population continues to expand the number of patients living with a diagnosis of cardiovascular disease (now estimated at 13 million for coronary heart disease alone) who might benefit from these therapies. Second, multiple studies of the use of these recommended therapies in appropriate patients, although showing slow improvement, continue to support the discouraging conclusion that many patients in whom therapies are indicated are not receiving them in actual clinical practice. The AHA and ACC recommend the use of programs such as the AHA’s Get With The Guidelines or the ACC’s Guidelines Applied to Practice to identify appropriate patients for therapy, provide practitioners with useful reminders based on the guidelines, and continuously assess the success achieved in providing these therapies to the patients who can benefit from them.
