ALGORITHM FOR THE DIAGNOSIS OF ANGINA PECTORIS, THE CHOICE OF
INVESTIGATIONS
While history often suffices to establish the diagnosis of angina pectoris, additional investigations are usually
needed to confirm the diagnosis, to assess prognosis and to select the most appropriate therapy. Different strategies may be followed depending on the patient’s previous history and the severity (frequency and intensity) of their symptoms. In patients with new symptoms, in whom the diagnosis of coronary artery disease has not yet been established, the approach will differ in comparison with patients with known coronary artery disease, after previous coronary angiography or coronary intervention or after previous myocardial infarction.
Three diagnostic strategies can be distinguished:
(1) It may be adequate to rely solely on the patient’s history, supplemented by physical examination
and a resting electrocardiogram. This approach often suffices in elderly patients with mild symptoms
responding promptly to medical therapy and in patients in whom coronary interventions are not
considered a therapeutic option.
(2) Another approach is based on a functional assessment of the presence or absence and extent of
myocardial ischaemia, which may include exercise testing with electrocardiography, exercise (or other
stress) myocardial perfusion imaging (thallium or one of the technetium-99 m labelled perfusion
tracers), stress-echocardiography and, possibly, exercise radionuclide angiography. In patients with
significant functional abnormalities, this may be followed by coronary angiography to assess whether
coronary intervention is indicated and which intervention would be most appropriate. The indications
for coronary angiography are discussed in more
*Equivalent to 100–200 m. detail below. Guidelines on management of stable angina pectoris 397
Eur Heart J, Vol. 18, March 1997
(3) A further option is to proceed immediately from history, physical examination and ECG to coronary
angiography. This approach may be indicated particularly in patients with typical and severe symptoms,
including unstable angina, patients with early post infarction angina, and in patients with early
recurrence of symptoms after previous coronary intervention[36].
In clinical practice, the second approach is followed most frequently. In patients with frequent or
severe stable angina, functional assessment is often useful prior to or in addition to angiography. It should
be appreciated that symptoms resembling angina do not necessarily have a causal relation to any coronary
artery narrowings present. Thus, additional functional assessment may be needed in patients with less typical
symptoms and moderately severe coronary artery narrowings. Furthermore, such an assessment may help
to establish the functional significance of abnormalities observed in the coronary angiogram[37]. For example, in a patient with both complete obstruction of one coronary vessel (and possibly previous myo- cardial infarction) and a moderately severe stenosis in another vessel, perfusion scintigraphy may help to decide whether symptoms are likely to be alleviated by percutaneous intervention (PTCA) of the moderately severe lesion only, or by surgical intervention of both vessels.
Table 1(a) Pretest likelihood of coronary artery disease in symptomatic patients according to age and sex
Table 1(b) Coronary artery disease post-test likelihood (%) based on age, sex, symptom classification and
exercise-induced electrocardiographic ST-segment depression
FUNCTIONAL ASSESSMENT, A MULTI-STAGED APPROACH TO
ESTIMATE THE PROBABILITY OF CORONARY ARTERY DISEASE
In patients without previous diagnosis of coronary artery disease, a stepwise approach can be followed to
assess the probability of significant coronary artery disease based on a combined analysis of factors such
as age, gender and the type of chest pain, as well as presence and degree of ST segment changes during
exercise (Tables 1 (a) and (b)). The probability of the presence of significant coronary artery disease can be
refined by analysis of the presence and degree of ST segment changes during exercise[38,39]. From the Table it is apparent that an exercise test will not be very useful to verify the diagnosis of coronary artery disease in a 64-year-old man with typical angina. Even in the absence of ECG changes during the test, the likelihood of coronary artery disease will still be 79%, while it would rise to 99% if 0·2 mV ST segment depression were to occur. Yet the test may help to determine the functional impairment of that patient (exercise tolerance), to measure the blood pressure response (as an indicator of left ventricular function) and to estimate prognosis. Similarly, the diagnostic value of exercise electrocardiography is low in asymptomatic men and women.
The greatest diagnostic value is obtained in patients with an intermediate pre-test likelihood, for
example between 20% and 80%. A further refinement is a multivariate analysis of stress test results[40,41], in
which the probability is estimated based on a combination of heart rate at peak exercise, ST segment depression, the presence or absence of angina during the test, workload achieved and ST segment slope. Such estimation of the likelihood of coronary artery disease provides more insight into the actual situation of a patient than an arbitrary classification of normal or abnormal. In patients with a low probability of coronary
artery disease (for example, <20%) and an adequate exercise tolerance, usually no further investigations will
be necessary, even though the presence of coronary artery disease can not be excluded. In patients with a
high post test likelihood (for example >80%) the diagnosis of coronary artery disease has been established. If
the symptomatology is moderately severe or severe, and not adequately controlled by medical therapy, coronary angiography is indicated to determine whether coronary intervention is warranted.
In patients with an intermediate post test likelihood (between 20 and 80%) after a stress test, a second
non invasive test will be helpful to distinguish between subgroups of patients with a higher or lower post test
probability. Depending on facilities and experience in a given environment, either myocardial perfusion scintigraphy or stress echocardiography may be chosen as a second test (Table 2). In principle, subsequent tests to improve diagnostic certainty should be requested only if the results would impact on patient management, including prescription of preventive measures. Often, no further tests are required in patients with mild symptoms and a normal exercise tolerance, even if the diagnosis remains somewhat uncertain. In contrast, additional stress test or angiography is warranted in patients with more severe
or frequent symptoms, particularly if these occur at low workload in the absence of electrocardiographic signs
of myocardial ischaemia. Additional stress tests with perfusion scintigraphy or echocardiography are often
useful in:
(1) Patients with typical anginal symptoms and nondiagnostic exercise ECG (ECG changes at rest
because of left ventricular hypertrophy, preexcitation or bundle branch block) or difficulty in
performing exercise due to non-cardiac limitations, or a normal exercise ECG with (moderately) severe
symptoms.
(2) Subjects with atypical angina or absence of symptoms with a positive exercise ECG (with the
exception of very abnormal changes).
(3) Special subgroups with typical angina and a positive exercise ECG where false-positive stress tests are
common, for example in younger women[42].
Table 2 Functional tests of coronary artery disease
It should be appreciated that the diagnostic approach to patients with chest pain of possible cardiac
origin has changed since the introduction of effective measures for prevention of progression of coronary
artery disease. In addition to an advice to stop smoking and treatment of hypertension and diabetes, patients
with known coronary artery disease may now require treatment with lipid lowering drugs, particularly cholesterol synthesis inhibitors (statins). It has been shown unequivocally that these drugs reduce the rate of progression of coronary disease[43,44] and reduce the incidence of coronary events.[45–47]. Since these drugs are costly, these should be prescribed for (secondary) prevention only in patients with documented coronary disease. Thus, it has become important to establish or rule out this diagnosis even in patients with mild symptoms in whom coronary intervention would not be considered.
Non-invasive investigations
Resting electrocardiogram (ECG)
All patients with the suspicion of angina pectoris based upon symptoms should have a resting 12-lead
electrocardiogram (ECG) recorded. This will not identify with certainty whether patients have coronary artery
disease or not; a normal resting ECG is not uncommon even in patients with very severe angina. However, the resting ECG may show signs of coronary artery disease such as previous myocardial infarction or an abnormal repolarisation pattern. In addition, the ECG may show other abnormalities such as left ventricular hypertrophy, bundle branch block, pre-excitation, arrhythmias or
conduction defects. Such information may be helpful in defining the mechanisms responsible for chest pain or in
identifying patient subgroups with a higher risk of death or myocardial infarction.
ECG stress testing
For patients with stable angina pectoris, the first investigation after clinical assessment and a resting ECG is
likely to be an exercise ECG. The exercise test should be carried out only after careful clinical evaluation of
symptoms and a physical examination including resting ECG. ECG changes during exercise are associated with
the presence of coronary artery disease with a sensitivity of around 70% and a specificity of approximately 90%.
The results of the ECG stress testing should be interpreted by trained clinicians[48,49]. In population studies
with a low prevalence of ischaemic heart disease the proportion of false positive tests will be high. Furthermore,
false positive exercise recordings are common in women with a low prevalence of disease. ECG changes
during exercise suggesting myocardial ischaemia in the absence of coronary artery disease are also seen in
patients with such conditions as syndrome X, digitalis treatment and electrolyte abnormalities.
In order to improve the specificity and sensitivity of exercise ECG to identify coronary artery disease the
test procedure should be standardized with the use of nomograms predicting the exercise response taking into
account age, gender and body size. The test may be conducted in patients taking anti-ischaemic drugs. A
‘normal’ test in such patients does not rule out significant coronary disease. Thus, a second test, with less or
no medication, may be indicated, depending on the clinical question to be answered[48].
The evaluation of the exercise test demands assessment of the pretest and post-test likelihood of
coronary disease in the particular patient under investigation (Table 1 (a) and (b)). The ECG should be
continuously recorded with a print-out of signal averaged recordings at preselected intervals, mostly at each
minute during exercise, and 4 to 10 minutes of recovery after exercise. An exercise test is commonly regarded as ‘positive’ if there is horizontal or downsloping ST-segment depression 0·1 mV in any lead. Such a dichotomous approach (i.e. ‘positive’ or ‘negative’) is to be deplored. It is misleading because in assessing the significance of the test, one should take into account not
only the ECG changes but also the work load, heart rate increase and blood pressure response, and the clinical
context. ST changes related to heart rate have been suggested to be more reliable, describing the slope of ST
segment changes over time[40,50]. Either the Bruce protocol or one of its modifications on a treadmill or a bicycle
ergometer can be employed. The bicycle work load is described in terms of Watts (W). Increments are of 20 W
per 1 minute 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[48]. A standard protocol should be employed, since this may be used for
future reference in the same patient. In addition to the diagnostic value of the exercise ECG, the stress test has
an important role in demonstrating silent ischaemia and in predicting the prognosis of patients with chronic
stable angina pectoris and following the progress of the disease or the effect of treatment.
The reason for stopping the test and the symptoms at that time, including their severity, should always
be recorded. Time to the onset of ECG changes and/or symptoms, the overall exercise time, the blood pressure
and heart rate response, and the post-exercise recovery pace of ECG changes should be assessed. The exercise
stress test is terminated at the discretion of the physician for one of the following reasons:
(1) Symptom limitation, e.g. pain, fatigue, dyspnoea; for repeated exercise tests. The use of Borg scale is
recommended to allow comparisons[51].
(2) Combination of symptoms such as pain with significant ST-changes.
(3) Safety reasons such as marked ST-segment changes (particularly ST-segment elevation), arrhythmias, or
a sustained fall in systolic blood pressure.
400 Guidelines on management of stable angina pectoris Eur Heart J, Vol. 18, March 1997
Ambulatory monitoring
The sensitivity and specificity of the ST segment changes for the diagnosis of coronary artery disease are lower
than for the exercise test, but may reveal evidence of myocardial ischaemia that is not provoked by exercise[
52,53]. Ambulatory electrocardiographic (Holter) monitoring rarely adds important clinical information
for assessment of the diagnosis of chronic stable angina pectoris over and above that provided by an exercise
test. Evaluation of repolarisation changes by ambulatory monitorning requires the use of equipment with
an adequate frequency response, according to the guidelines for electrocardiography. Two-lead or three-lead
recordings are used most frequently and should include a bipolar V5 chest lead. Recording of twelve-leads by
ambulatory monitoring may have advantages.
Echocardiography at rest
Two-dimensional echocardiography is useful to estimate the size of the heart chambers and regional and
global left ventricular function. In addition, M Mode echocardiography offers accurate and reproducible
measurements of cardiac chamber dimension and wall thickness, although the geometry in patients with coronary
artery disease is often complex due to myocardial infarction, remodelling and aneurysms. Measurements
of left ventricular performance during systole and diastole may include ejection fraction, ejection time intervals,
and systolic and diastolic volumes, wall stress, stroke volume, cardiac output and the diastolic Doppler
flow pattern. Echocardiography is also useful to rule out the possibility of other disorders such as valvular heart
disease or hypertrophic cardiomyopathy as a cause of symptoms[54].
Stress echocardiography
Stress echocardiography has been developed as an alternative to ‘classical’ exercise testing with electrocardiography,
and as an additional investigation to establish the presence or location of myocardial ischaemia during
stress.
At least 10 to 20% of patients referred for evaluation of chest pain are unable to perform an
adequate diagnostic ECG exercise test. In these patients dobutamine stress echocardiography represents an
alternative exercise independent stress modality. Yet it should be appreciated that 5% of patients have an
inadequate echo window and 10% of the patients referred for a dobutamine stress test have a non-diagnostic
result (submaximal negative test). The methodology and interpretation of stress
echocardiography has been described in several excellent reviews[55,56]. In short, the heart is stressed
by infusion of dobutamine or similar substances. Dobutamine is administered intravenously starting
at 10 ìg . kg"1 . min"1 for 3 min, increasing by 10 ìg . kg"1 . min"1 every 3 min to a maximum of
40 ìg . kg"1 . min"1, which is continued for 6 min. In patients not achieving 85% of their age-predicted maximal
heart rate, who have no symptoms or signs of ischaemia, atropine is given at the lower stage (0·25 mg
injections to a maximum of 1·0 mg) while dobutamine is continued. Throughout the test the ECG is monitored,
and full 12 lead ECG recordings are made every minute. The two-dimensional echocardiogram is continuously
monitored on a quad screen display for side by side examination of rest and stress images, and recorded by
video, or on digital equipment. Normal myocardium shows an increase of movement and thickening during
stress, while ischaemia is recognized by reduced regional wall thickening and transient regional wall motion
abnormalities. It should be appreciated that proper interpretation of changes in wall motion on a stress
echocardiogram requires considerable, experience and expertise. Optimal recording equipment and computer
display (quad screen) is essential. In experienced hands this method can become an excellent tool to clarify
regional wall motion abnormalities due to coronary disease.
Myocardial perfusion scintigraphy
Myocardial perfusion scintigraphy is usually performed in association with a symptom limited exercise test on
either a bicycle ergometer or a treadmill. It offers a somewhat more sensitive and specific prediction of the
presence of coronary artery disease than exercise electrocardiography and allows detection of the location of
myocardial ischaemia during exercise. Isotopes used most frequently are thallium 201 and technetium-99 m
labelled perfusion tracers. The isotope is injected at peak exercise, preferably at the time when a patient experiences
symptoms compatible with myocardial ischaemia. Images are made immediately (thallium) or shortly after
exercise and repeated a few hours later, or the next day after a new injection of the tracer. In patients who are
unable to exercise adequately, infusion with dobutamine or similar agents may be used to stress the heart. A third
approach is the use of vasodilators (dipyridamole or adenosine) to enhance perfusion in areas supplied by
‘normal’ coronary arteries. Myocardial ischaemia, or underperfused areas after vasodilatation, can be recognized as an area with
diminished isotope uptake during exercise in comparison with the uptake at rest. Interpretation of the test can
be facilitated by semi-quantitative analysis and tomographic display (SPECT=single photon emission computer
tomography). Sensitivity and specificity for perfusion scintigraphy are similar to those obtained with
stress echocardiography. Increased uptake of thallium 201 in the lung field identifies patients with extensive
coronary artery disease[57–60].
Guidelines on management of stable angina pectoris 401 Eur Heart J, Vol. 18, March 1997
Radionuclide angiography during exercise
Radionuclide angiography using technetium labelled red blood cells can be used to assess left ventricular function
(global ejection fraction and regional wall motion) at rest and during exercise. For these studies exercise is
conducted in the supine position with stepwise increments in work load with a 3 to 5min step duration.
Images are collected over 1 to 2 min on each exercise stage. Healthy subjects will show a normal ejection
fraction at rest which increases on exercise, while patients with coronary disease (or other types of left
ventricular dysfunction) often exhibit no increase or a decrease of global ejection fraction as well as development
of regional wall motion abnormalities during exercise[57,58].
Coronary angiography
Coronary angiography has a pivotal position in the management of patients with chronic stable angina
pectoris. It is currently the most reliable tool to ascertain the anatomical severity of coronary artery disease. However,
necropsy and ultrasound studies[61] have clearly demonstrated that the extent of plaque mass is grossly
underestimated by this technique. It carries a small risk of mortality (<0·1%)[62] and often needs to be supplemented
by functional tests.
Indications.
Taking into account the development of new techniques of myocardial revascularization and the low risk of complications of coronary angiography, it should be considered in the following conditions:
(1) Severe stable angina (Class 3 of the Canadian Cardiovascular Society Classification (CCS)), particularly
if the symptoms are inadequately responding to medical treatment;
(2) Chronic stable angina (Class 1 to 2) if there is a history of myocardial infarction or evidence of
myocardial ischaemia at a low work load;
(3) Chronic stable angina in patients with bundle branch block if readily-induced ischaemia is demonstrated
by myocardial perfusion scintigraphy;
(4) Patients with stable angina who are being considered for major vascular surgery (repair of aortic aneurysm, femoral bypass, or carotid artery surgery);
(5) Patients with serious ventricular arrhythmias;
(6) Patients previously treated by myocardial revascularization (PTCA or CABG) who develop recurrence
of moderate or severe angina pectoris;
(7) When it is essential to establish the diagnosis for clinical or occupational reasons.
T
he performance and interpretation of coronary angiography must be irreproachable. A complete examination
includes left ventricular cineangiography perform ed in the right arterior oblique projection together
with a ventriculogram in the left oblique projection. This permits assessment of left ventricular function including
wall motion abnormalities. The left coronary artery is usually examined in five projections, to ensure optimal
assessment of each specific coronary segment, and the right coronary artery in at least two projections. Recording
of overlapping segments must be avoided and specific, steeply angulated caudal left and right anterior
oblique projection must frequently be used. Interpretation of the arteriogram includes description of the
morphology and severity of coronary lesions, together with the presence of collateral vessels.
Most angiographers tend to overestimate the degree of stenosis prior to intervention, and underestimate
the residual narrowing after treatment[63,64].
Quantitative coronary angiography greatly improves the accurate assessment of coronary stenoses. In clinical
practice, assessment and, even more, the treatment of a 50–75% stenosis must be complemented by evaluation of
its physiological importance with the usual markers of ischaemia. In a diffusely narrowed and/or small vessel,
it is preferable not to use the percentage of stenosis but to use the absolute value (mm) of the minimal
lumen diameter (MLD). In general, an MLD<1 mm in a proximal vessel indicates a flow-limiting stenosis,
regardless of the percentage diameter stenosis. In conclusion, coronary angiography has
evolved into a routine examination. It provides a considerable body of information for establishing the diagnosis
and assessing the prognosis of coronary artery disease. Nevertheless, the decision to perform this examination
must be based on the clinical and physiological findings derived from a careful review of the history
and evidence of myocardial ischaemia. In selected patients, objective intravascular ultrasound
may provide additional information regarding the status of plaques and the presence or absence of intracoronary
thrombosis. The measurement of fractional flow reserve[65] is a promising new technique for assessment
of the functional significance of stenoses. These methods are still under investigation.
TREATMENT
Aims of treatment
To improve prognosis by preventing myocardial
infarction and death
In order to achieve this end, attempts must be made to induce regression or halt progression of coronary
atherosclerosis, and to prevent complications, especially thrombosis. Lifestyle changes and drugs play a vital role
in this, but the myocardium may also be protected if its perfusion is enhanced by interventional techniques.
To minimize or abolish symptoms
Lifestyle changes, drugs, and interventional techniques all play a part.
402 Guidelines on management of stable angina pectoris
Eur Heart J, Vol. 18, March 1997
General management
Patients and their close associates should be informed of the nature of angina pectoris, and the implications of the
diagnosis and the treatments that may be recommended. The patient can be reassured that, in most cases, angina
improves with proper management. Risk factors, especially smoking habit and lipid levels, should be assessed
in all cases. Particular attention must be paid to elements of the lifestyle that could have contributed to the
condition and which may influence prognosis. The recommendations of the European Task Force[66] on ‘Prevention
of Coronary Heart Disease in Clinical Practice’ should be followed.
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[67,68]. Cessation of
smoking greatly impoves both symptoms and prognosis. Patients often require special help in abandoning their
addiction, and transdermal nicotine has proved effective and safe in helping patients with coronary artery disease
to quit smoking.
Diet. Patients should be encouraged to adopt a ‘Mediterranean’ diet, with vegetables, fruit, fish and
poultry being the mainstays. The intensity of change needed in the diet depends upon the total (LDL) plasma
cholesterol level and other lipid abnormalities[69]. Those who are overweight should be put on a weight reducing
diet. Alcohol in moderation may be beneficial[70], but excessive consumption is harmful, especially in patients
with hypertension or heart failure.
Hypertension, diabetes and other disorders. Concomitant disorders should be managed appropriately. Particular
attention should be given to control of elevated blood pressure and diabetes mellitus. Both increase the risk
of progression of coronary disease, particularly when ill-controlled. Also anaemia, if present, should be
corrected.
Physical activity. Physical activity within the patient’s limitations should be encouraged, as it may increase
exercise tolerance[71], and 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 individuals’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[72].
Psychological factors. While the role of stress in the genesis of coronary artery disease is controversial, 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[73].
Car driving. In most countries, patients with stable angina are permitted to drive except for commercial
public transport or heavy vehicles. Stressful driving conditons should be avoided.
Sexual intercourse. Sexual intercourse may trigger angina. Common sense will dictate that this should
not be too physically nor emotionally demanding.Nitroglycerin prior to intercourse may be helpful.
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 patients with
chronic stable angina
Pharmacological treatment of angina encompasses both the prevention of the complications of coronary
atherosclerosis and the relief of symptoms.
The prevention of myocardial infarction and death
In recent years, it has become clear that drugs that modify lipids or decrease the risk of thrombosis substantially
improve prognosis with regard to the incidence of both myocardial infarction and death. Nitrates and
calcium antagonists have not been shown to be effective in this respect, but large trials have established that, at
least in the post-infarction patient, betablockers reduce mortality and reinfarction.
Lipid-lowering drugs.
All patients with angina pectoris should have a lipid profile. The Scandinavian Simvastatin Survival Study[45] showed that a statin, given to patients with angina pectoris and a total cholesterol level between 5·5 and 8·0 mmol . l"1 (212 and 308 mg . dl"1),
substantially reduces the risk of myocardial infarction, death, and the need for coronary bypass surgery. Supportive
evidence from other trials suggests benefit at even lower lipid levels[46,47]. Previous concerns about the
risks of lipid-lowering have now been allayed. Indications for drug therapy depend upon the overall risk of
the patient[66,74]. If diet fails to reduce the cholesterol level, lipid-lowering drugs should be prescribed with the
aim of reducing the total cholesterol level to below 5·0 mmol . l"1 (192 mg . dl"1) and LDL cholesterol below
2·6 mmol . l"1 (100 mg . dl"1). The choice of lipidlowering regimen will depend upon the lipid-profile.
Aspirin.
An overview of trials of antiplatelet agents in 3000 patients with stable angina showed a 33%
Guidelines on management of stable angina pectoris 403 Eur Heart J, Vol. 18, March 1997 reduction in vascular events[75,76]. It is recommended that aspirin is administered routinely in a dosage of 75–160 mg daily in the absence of contra-indications.
Hormone replacement therapy (HRT).
Epidemiological evidence strongly suggests a beneficial effect of HRT in patients without manifest coronary disease. Although
there is little information on the benefits and safety of HRT in anginal patients, there is no reason not to use
these drugs where indicated in patients with coronary artery disease.
Anti-oxidants.
The theoretical benefits of anti-oxidant therapy have not yet been confirmed in adequate trials.
Further studies are needed before this therapy can be recommended for angina patients.
Drugs for symptom relief
Three main classes of drugs are used to control symptoms in chronic stable angina:nitrates, beta-blockers and
calcium antagonists[77]. Given in appropriate regimens, all these agents can be effective in this context, but there
is a considerable and, to a large extent, unpredictable variation in response and adverse effects. The aim of
anti-anginal treatment is to reduce the myocardial oxygen requirements or to increase myocardial perfusion.
Often, it may be possible to achieve both aims.
Nitrates.
Sublingual nitrates work rapidly, i.e. within minutes, and the effect lasts for about 30–45 min. Profound relief of symptoms is the result of venodilatation, afterload reduction and coronary dilatation. Many nitrate delivery systems have been developed for
chronic prophylactic use. It has become clear, however, that patients can develop at least partial tolerance to
this therapy. The use of nitrate-free interval between dosing is an effective means of overcoming the development
of tolerance, although in some cases a rebound of symptoms may occur at this time. This can be
obviated by the concomitant use of another class of anti-anginal agent. Nitrates did not influence morbidity
or mortality in the 4–6 weeks after myocardial infarction in the ISIS-4[78] and GISSI-3[79] trials. There have
been no long-term trials of nitrates in patients with chronic stable angina.
The main adverse effect of nitrates is headache, which may be troublesome but tends to diminish with
continued use. Other side-effects include flushing and syncope. Nitrates are particularly indicated for the
prompt relief or prevention of angina and are also of value long-term in patients with heart failure or with
contra-indications to beta-blockers. They are often (but not always) effective in patients with vasospastic angina
and in syndrome X.
â-blockers.
â-blockers act mainly by blocking the â1 receptor. ‘Non-selective’ â-blockers also block the â2
receptor but even ‘selective’ â-blockers have some effect upon this receptor, especially at higher dosages. Blockade
of the â1 receptor slows the heart rate and reduces myocardial contractility; both these effects reduce
myocardial oxygen demand and thereby the severity of ischaemia. All â-blockers when given in adequate
dosages help to prevent anginal attacks.
Selective â-blockers are generally to be preferred in patients suffering from asthma, peripheral vascular
disease and insulin-dependent diabetes, although they are not entirely safe in these contexts. Some more
recently developed agents cause peripheral vasodilatation and may be more useful in cases of peripheral
vascular disease. Major adverse effects include severe bradycardia, hypotension, brochospasm and, rarely,
heart failure, but these are uncommon if patients are appropriately selected. More subtle side-effects, which
may go unrecognised unless sought, include fatigue, lassitude, nightmares, and cold extremities.
The effect of â-blockers on the prognosis of stable angina has not been specifically studied in a large
trial. A history of angina has, however, been present in about one-third of the patients recruited into postinfarction
studies of these agents. The Beta-Blocker Pooling Project[80] reported a highly significant reduction
in mortality in this sub-group, and it seems reasonable to assume that â-blockers have the potential to
prevent death, especially sudden death, and the development of myocardial infarction even when there has been
no prior infarction. â-blockers are indicated for most patients with more than the mildest angina, in the absence of contraindications. They are particularly indicated in the postinfarction patient.
Calcium antagonists.
Calcium antagonists cause coronary and peripheral vasodilation. Furthermore, smooth muscle relaxation and reduction of afterload together with the negative inotropic effects of some of the agents will reduce myocardial oxygen consumption. While
various formulations of the two prototype papaverinelike and benzothiazepine-like calcium antagonists—
verapamil and diltiazem— are widely available, most current development involves analogues of the
nifedipine-like dihydropyridine class. The calcium antagonists are a structurally heterogeneous group of compounds
with important differences in pharmacological action.
Verapamil slows conduction through the atrioventricular node and has important negative inotropic
effects as well as causing smooth muscle relaxation which leads to an increase in coronary blood flow and a
reduction in afterload. The dihydropyridines, such as nifedipine and amlodipine, also cause smooth muscle
relaxation but have no effect on cardiac pacemaker tissue which may result in a reflex increase in the heart
rate. In common with other calcium antagonists, these drugs have negative inotropic effects, which are, however,
less marked than those of verapamil. The effect of diltiazem is similar to those of verapamil though it has a
less potent effect of left ventricular function.
The calcium antagonists in general should be used with caution in patients in heart failure or with 404 Guidelines on management of stable angina pectoris Eur Heart J, Vol. 18, March 1997 poor left ventricular function, although some long acting
dihydropyridines, such as amlodipine, may be safer in this context.
Unlike â-blockers, calcium antagonists have not been shown to reduce mortality after myocardial infarction,
although there is some evidence that verapamil and diltiazem may reduce the risk of reinfarction[81,82].
Concerns have been expressed about the safety of calcium antagonists, particularly the short-acting preparations[
83]. Calcium antagonists should be considered if beta-blockers are contra-indicated or ineffective. They
are specifically indicated for vasospastic angina.
Other agents.
Molsidomine belongs to a newly discovered class of sydnonimines, which resemble nitroglycerin
in their mode of action. Molsidomine appears to act more slowly than nitrates, but its effect lasts longer.
Nicorandil, a potassium channel activator, also possesses nitrate-like activity. It relaxes vascular smooth
muscle; and does not appear to cause tolerance with chronic dosing. Metabolic agents, such as trimetazidine,
may also be useful.
Combination treatment.
Many but by no means all studies have demonstrated additional beneficial antianginal effects when a beta-blocker is used in combination with a calcium antagonist or a long-acting nitrate preparation. Care needs, to be taken however, with the
combination of a â-blocker and verapamil or diltiazem, especially if there is evidence of conduction disturbance
or left ventricular dysfunction. Furthermore, calcium antagonists may be combined with long-acting nitrates.
The effects of combining drugs may be due to an additional reduction in the rate-pressure product both at
rest and on exercise, but the IMAGE study[84] suggests that the benefit of adding a new agent may be due to the
recruitment of new reponders than to combination per se. In addition, synergy between two classes of drug may
abolish the potentially detrimental effects of each. There is little evidence to support the current vogue of using
triple therapy. Indeed as Tolins et al.[85] have emphasized, ‘maximal’ therapy is not necessarily optimal
therapy.
Choice of anti-anginal agent.
All patients should be offered short-acting nitrates either sublingually or by spray. These drugs may be used not only to treat an
acute episode but are particuarly valuable taken prophylactically when an attack is anticipated, for example
prior to exercise.
Choice of first line treatment for prophylaxis depends on the underlying predominant pathophysiological
process, left ventricular function, and associated conditions. Patients with very clear-cut effort-related
angina should be offered a beta-blocker as should those with a prior myocardial infarction. Diltiazem and verapamil
are also useful in such circumstances though they should be avoided in the presence of significant left
ventricular dysfunction. Nitrates are of value where there is left ventricular dysfunction; â-blockers and some
vascular selective long-acting dihydropiridines can also be given cautiously in such circumstances. Patients with
asthma and peripheral vascular disease may be best treated with a long acting nitrate or a calcium antagonist,
although selective â-blockers may be given with caution. As mentioned above, various combinations of
â-blockers, nitrates and calcium antagonists have been shown to be useful where a single agent is ineffective, but
it is probably best to evaluate an alternative single drug before starting combination treatment.
Percutaneous transluminal coronary
angioplasty
Percutaneous transluminal coronary angioplasty (PTCA) is widely used in the treatment of stable angina
pectoris. Introduced in 1977 by Grüntzig, the number of procedures has increased exponentially and angioplasty
has surpassed the frequency of coronary bypass graft surgery (CABG). This dramatic increase is largely the
result of major changes in the technique, the materials, and lesion selection criteria. The introduction of better
imaging systems has also contributed to the great improvements in results that have been seen. In the
majority of cases, the procedure is achieved with a balloon tracking over a guide wire. Alternative methods
may be preferred for particular types of lesions. Large bulky, eccentric lesions are good indications for directional
atherectomy. Ablation with a Rotablator is most effective in the treatment of hard, fibrocalcific lesions,
ostial lesions, and diffuse disease. Earlier enthusiasm for laser therapy has declined because of the frequent need
for adjunctive balloon angioplasty and a high rate of restenosis. By contrast, stents are used more and more
frequently in coronary interventional cardiology. Better deployment and new management after stent implantation
have increased the safety of coronary stenting and led to a low risk of subacute thrombosis and vascular
complications[86]. Stents have markedly decreased the need for emergency CABG, the rate of post procedure
myocardial infarction, and restenosis.
Success and risks.
In stable angina pectoris, a procedural success in anatomically suitable patients is achieved in
95% of cases[87]. The mortality rate is less than 0·2% in patients with single vessel disease and 0·5% in case of
multivessel disease. The need for emergency bypass surgery is currently less than 1% since the advent of
stents. The rate of myocardial infarction, as recognised by developments of new Q waves, is now less than 1%.
These results can be achieved within a short period of hospitalisation. Furthermore, the use of small
(6 F) catheters allow simple lesions to be treated on a day case basis. The return to work is rapid.
Restenosis.
Restenosis remains a major concern. It occurs in 35 to 40% of cases with angiographic control.
In some cases, restenosis is detected by the recurrence of symptoms but it can be completely silent and detected
Guidelines on management of stable angina pectoris 405 Eur Heart J, Vol. 18, March 1997
only by systematic angiography. Non-invasive tests are not very predictive (predictive value 50% if positive) but
have a good negative predictive value (93%). There are two principal mechanisms of restenosis: chronic recoil of the artery (remodelling)[88] and neo-intimal proliferation (healing process). In more than 50 randomised multicentre trials, drugs have failed to
prevent neo-intimal proliferation perhaps because they attacked only one (relatively limited) of the mechanisms.
Recently, trials with c73E3 Gp IIb/IIIa receptor blockade have indicated a reduction in death and myocardial
infarction after PTCA[89]. The remodelling process can be prevented by stent implantation which significantly
decreases the rate of restenosis in patients with stable angina and vessels with diameters between 2·6 and
3·4 mm. The combination of stent implantation and a drug locally or generally delivered could lead in the near
future to a marked reduction in the rate of restenosis. When the patient experiences recurrence of chest pain
and significant restenosis, a repeat PTCA with or without stent implantation can be performed. The risk of this
reintervention is low and the success rate high.
Comparisons of PTCA and drug treatment.
There is, as yet, no convincing evidence that PTCA is superior to medical treatment with regard to the risk of myocardial
infarction or death in patients with chronic stable angina. The decision whether to undertake PTCA in
such patients depends, therefore, on the anticipated benefit to be obtained in respect of angina. Few comparative
trials have been undertaken to address this issue. In the ACME trial[90,91], a randomized study
comparing PTCA vs medical therapy in single LAD disease, PTCA decreased the incidence of symptomatic
ischaemia and was associated with more normal treadmill exercise tests. However, 48% of the medically
treated patients were rendered free of angina compared with 64% of the PTCA group, and PTCA was associated
with a higher frequency of complications and greater expense.
Coronary bypass graft surgery
Coronary bypass graft surgery has been recognised as a very effective method of myocardial revascularisation
for more than 25 years. Coronary artery surgery is now a reproducible and technically precise procedure. Patient
survival and freedom from events are dependent to an important degree on attention to technical details. The
coronary bypass operation is usually performed with cardiopulmonary bypass using the pump oxygenator,
although less invasive techniques are being increasingly employed. A number of methods of minimising perioperative
ischaemia and numerous strategies for myocardial management are in use.
Conduits for coronary bypass graft surgery.
Several autogenous conduits are available. The long saphenous vein is still widely used, but if possible, arterial grafts are
preferred because their long-term patency is superior to that of saphenous vein graft. The left internal mammary
artery is incorporated in almost all bypass procedures of the left coronary artery. The right internal mammary
artery, may also be used. Other conduits, such as the right gastro-epiploic artery and inferior epigastric artery
may also be considered. Endarterectomy is most often reserved for vessels with distal disease not satisfactory
for distal grafts. This method is most commonly applied to the right coronary artery at and beyond the crux.
It has been shown that endarterectomy is associated with a higher perioperative mortality and myocardial
infarction whilst a lower long-term graft patency is frequently observed.
Risks and complications.
The in-hospital major complications
largely depend on the extent of vessel disease,
left ventricular function and associated diseases (renal or
respiratory insufficiency). The in-hospital mortality rate
is 1% in single vessel disease and increases up to 4 to 5%
in multivessel disease with poor left ventricular function.
Perioperative myocardial infarction characterized by the
occurrence of new Q waves may be observed in 4 to 5%
of cases[92].
Patency of the conduits. The patency rate of saphenous vein grafts is quite variable but 10 to 20% of grafts are
occluded within one week of surgery from thrombosis. By 3 to 5 years after operation, 60–70% of vein grafts
have evidence of atherosclerotic narrowing[93]. This new disease is characterized by very soft, friable material
which is very prone to embolize to the distal part of the vessels. By contrast, 90% of the internal mammary
artery grafts anastomosed to the left anterior coronary artery are patent 10 years after operation[94]. The risk of
re-operation is high, the 5 to 11% mortality rate depending mainly on the LV function.
Comparison of CABG with medical therapy.
Yusuf et al.[95] have undertaken a systematic review of the outcomes of 2649 patients randomly assigned to receive
CABG or medical management for coronary artery disease in seven individual trials conducted between
1972 and 1984. This meta-analysis demonstrated that CABG reduced mortality in patients with left main
disease and others at relatively high risk, such as those with three vessel disease associated with impaired left
ventricular function.
Comparison of PTCA vs CABG.
Five major randomised trials have compared these two forms of intervention, mainly in patients with multiple vessel disease. Three
were conducted in Europe (RITA[96], GABI[97] and CABRI[98] and two in U.S.A. (EAST[99] and BARI[100].
Only one (RITA)[96] compared the results of PTCA and CABG in patients with single vessel disease.
The results of these trials are uniform and consistent:both methods of myocardial revascularization
were associated with a similar risk of death and nonfatal myocardial infarction, although the trials were
406 Guidelines on management of stable angina pectoris Eur Heart J, Vol. 18, March 1997
underpowered to detect small differences between both methods or differences among specific patient subgroups.
CABG involved a longer hospitalization and convalescence but thereafter, patients had less angina
and required fewer anti-anginal drugs. PTCA is a simpler method, without thoracotomy, general anaesthesia,
or exposure to nosocomial infection, but, subsequently, patients, particularly women, were more likely
to complain of angina, take anti-anginal drugs and undergo further revascularization procedures. In the
BARI trial, treated diabetics (insulin or oral therapy ) had a significantly lower 5-year mortality rate with
CABG than with PTCA (19% versus 35% P<0·02). In contrast, the mortality rate in diabetics not on drug
treatment was 9% for both therapies. Over 2 years, the cost of a treatment policy commencing with PTCA is
around 80% of a policy based on CABG. In evaluating these studies, it has to be borne in mind that all are
relatively short term, and that in the long-term further interventions are likely to be necessary in both groups as
native vessel coronary disease progresses. The high risk of repeat CABG may then become an important issue,
while angioplasty should be considered as a repeatable low risk procedure.
The choice of treatment in stable angina
pectoris
In selecting a treatment programme for patients with stable angina pectoris, the physician must constantly
bear in mind the two aims of treatment— to improve prognosis and to relieve symptoms. This strategy is
based on four pieces of information: a careful history, the response to some form of stress testing, ventricular
function, and the extent of coronary artery disease. Other factors have obviously to be taken into consideration,
such as age, gender, and comorbid conditions (pulmonary or renal disease, for example).
General management. It must be stressed that all patients, whether or not they are candidates for intervention,
should adopt those lifestyle changes that improve prognosis such as stopping smoking and a
lipid-modifying diet. Aspirin should be given as a routine in the absence of contra-indications, and lipidmodifying
drugs should be added if cholesterol remains high in spite of a diet.
Medical treatment vs intervention.
When first seen and regularly thereafter, the physician should consider whether the patient is at high risk of death. If so, and
if investigations show that the prognosis would be improved by surgery, this should be undertaken, irrespective
of the severity of the symptoms. Otherwise, medical treatment should be initiated. If symptoms are
not adequately controlled after some weeks of what is considered to be optimal medical management, the
indications for PTCA and CABG should be reviewed.
Choice of intervention (Fig. 1).
In deciding whether PTCA or CABG should be selected, the following considerations should be taken into account:
High risk patients with significantly impaired LV function.
CABG is recommended in patients with poor LV function (EF <30%) and left main coronary artery disease. If the left main artery has been surgically bypassed, PTCA of that artery (with or without the help of LV assistance) may be performed. The high
risk of acute and chronic recoil leading to restenosis necessitates stent implantation in this case. CABG is
also recommended for a single remaining vessel. CABG is indicated for abnormal LV function and triple
vessel disease, particularly when the proximal LAD is involved.
Associated severe co-morbid conditions.
In some cases, such as severe renal failure or pulmonary insufficiency, CABG may be contraindicated. PTCA, with or without
the help of a left ventricular assistance device (cardiopulmonary support), can be used.
Patients with normal or mild impairment of LV function.
Patients with left main narrowing should be treated by surgery. Triple vessel disease including proximal LAD
stenosis could be considered for CABG in most of the cases but, depending on the characteristics of the lesions
and if complete myocardial revascularization is possible, PTCA could be performed. Patients with double vessel
disease may be treated by coronary angioplasty, even in cases with a totally occluded vessel : Subgroup analysis
of CABRI showed that in this particular group of patients, there was no difference in terms of survival or
non-fatal MI between the two techniques of myocardial revascularization. Patients with single vessel disease
should be treated with angioplasty rather than with CABG.
Special subgroups
Women
Figure 1 Factors in the choice of intervention. Guidelines on management of stable angina pectoris 407
Eur Heart J, Vol. 18, March 1997 coronary artery disease is assumed to be less likely, chronic stable angina pectoris may be underdiagnosed. Symptoms of chest pain in women are often atypical and therefore dismissed, particularly if the woman is young.
Furthermore, because the prevalence of coronary artery disease in younger women is low, the exercise test is
more likely to be falsely positive. This explains the more frequent prevalence of chest pain with normal coronary
arteries in women (five times that of men) and therefore the better prognosis for women with ‘angina’ who have
been evaluated without angiography as a baseline[103]. The diagnostic value of exercise stress testing is lower in
women[104], primarily because of the lower prevalence of coronary artery disease. Women who can exercise to
stage III of the Bruce protocol or who have ST-segment normalisation within 4 min postexercise are unlikely to
have coronary artery disease[105]. Microvascular disease (syndrome X) may provoke chest pain in women due to
myocardial ischaemia despite angiographically normal arteries[106]. Women are less likely to be referred for
coronary angiography than men and women referred for chest pain who subsequently underwent coronary angiography
are found to have normal coronary arteries more often than men[107]. Due to the high frequency of
false positive exercise ECG tests, myocardial perfusion scintigraphy or stress echocardiography should more
often be considered. Women with typical angina symptoms on effort with positive exercise ECG or myocardial
perfusion defects should have access to coronary angiography.
There is no justification for treating men and women differently after coronary artery disease is diagnosed.
Women have a higher morbidity and mortality when suffering myocardial infarction than men after
taking into account known adverse factors and correcting for age. There are suggestions that treatment of
myocardial infarction is less vigorous in women than in men and that survival chances are reduced in women
discharged after myocardial infarction because they do not have the same therapeutic interventions as men[108].
There is a need to improve detection and treatment of coronary artery disease in women; when diagnosed
they have the same benefits from medical therapy and revascularization.
The elderly
After the age of 75 years there is an equal prevalence of coronary artery disease in men and women[109]. The
disease is more likely to be diffuse and severe; left main coronary artery stenosis and triple vessel disease are
more prevalent in older patients, as is depressed left ventricular function[110]. Coexistent illness or a sedentary
lifestyle may limit the usefulness of exertional chest pain as a diagnostic finding and exercise testing is less often of
diagnostic value for technical reasons. Due to the diffuse distribution of coronary artery disease, there is a higher
likelihood of non-specific ECG changes during the stress test[48]. In general, elderly patients with anginal
symptoms should be evaluated and managed in the same way as younger ones. With increasing age, however,
many patients are willing to accept a less well proven diagnosis of chronic stable angina pectoris and to start
treatment for evaluation of its efficacy. This means that not all elderly patients need be referred for exercise stress
testing, especially when noncardiac factors might limit the test.
Changes in drug bioavailability, elimination and sensitivity mean that dose modification is essential when
prescribing cardiovascular drugs to elderly patients[111]. Further issues which should be taken into account when
prescribing for the elderly include risk of drug interactions, polypharmacy and compliance problems.
Although evidence suggests that doctors may be reluctant to treat angina aggressively in very old patients, the
usual antianginal medications are as efficacious in this patient population as in the young. On the other hand,
elderly patients have a higher incidence of contraindications, complications and therapy withdrawals. Considering
symptoms as well as prognosis, elderly patients have the same benefit from medical therapy, angioplasty
and bypass surgery as younger patients[112,113,114].
Syndrome X
A significant proportion of patients undergoing diagnostic coronary angiography for chest pain show normal or
near normal coronary arteries. It has been reported that 6 to 30% of the patients fall into this category[115,116].
The term syndrome X is often used if patients with normal angiograms have angina-like chest pain and a
positive exercise stress test[115]. Angina with a normal coronary angiogram is clearly a heterogeneous condition
and a noncardiac cause, e.g. oesophageal disease is probably common[117]. In subsets of patients, myocardial
ischaemia can clearly be provoked and a reduced coronary vasodilator reserve has been demonstrated in
these patients. There are observations suggesting that patients with syndrome X may have an endothelial
dysfunction[118].
Patients with angina pectoris and normal coronary arteries have a good prognosis regarding mortality[
119]. This is important information for the patient who often has severe chest pain, functional limitation
and psychological distress. Patients with syndrome X are considered to respond poorly to conventional pharmacological
treatment. Sublingual nitrates are reported to relieve chest pain in only about 50% of the patients[115].
Conventional anti-ischaemic treatments have less consistent benefits. Since there is a female predominance in
angina with normal coronary arteries and the symptoms commonly start after menopause, a pathogenetic role of
oestrogen deficiency has been suggested[120]. Hormone replacement therapy may be useful[121].
Logistics of care
The organisation of medical care varies greatly from one country to another, and no uniform role can therefore
408 Guidelines on management of stable angina pectoris Eur Heart J, Vol. 18, March 1997
be assigned to the generalist or specialist respectively. In those countries in which general practitioners or other
generalists play a major role, it is important to recognise both their potential contribution and their limitations in
the management of angina. Because of their usually better knowledge of the patient and his or her personal
circumstances, they are often best placed to assess the whole individual and to advise on and supervise lifestyle
modifications, as well as compliance with therapy. However, specialist assessment is virtually always necessary
with regard to establishing the diagnosis and assessing severity and prognosis. Chest pain clinics which can
review patients without delay are of considerable value, particularly in patients with recent onset or suspected
unstable angina.
Conclusions and recommendations
(1) Stable angina pectoris due to coronary atherosclerosis is a common and disabling disorder. While
compatible with longevity, there is a substantial risk of progression to myocardial infarction, and/or
death. With proper management, the symptoms can usually be controlled and the prognosis substantially
improved. In practice, it seems probable that there is both widespread underdiagnosis and
overdiagnosis, and that optimal management strategies are often not implemented.
(2) Every patient with suspected stable angina requires prompt and appropriate cardiological investigation
to ensure that the diagnosis is correct and that the prognosis is evaluated. As a minimum, each patient
should have a carefully taken history and physical examination, an assessment of risk factors and a
resting electrocardiogram. Ready access to diagnostic facilities should be available to general practitioners.
Cardiology Departments should ensure that such patients are attended to without delay;
some hospitals now provide a special Chest Pain clinic for this purpose.
Three diagnostic strategies may be followed depending upon patient characteristics and the severity of
symptoms:
(a) The minimal assessment, as described above, without additional investigations. This may suffice, particularly
in elderly patients with readily controlled symptoms, or in those disabled or seriously ill for other
reasons.
(b) An initial non-invasive strategy which is appropriate for most patients. This allows an assessment
of the likelihood of and the severity of coronary heart disease in patients with mild to moderate symptoms e.g.
exercise testing with or without perfusion scintigraphy or stress echocardiography. In many patients, this may
lead to coronary angiography.
(c) Coronary angiography without prior functional testing. This may be an option for patients with
uncontrolled severe symptoms in whom revascularisation seems indicated urgently.
(3) It is essential in interpreting the findings of the exercise test, that the demographic and clinical features
of the individual are taken into account, as well as the workload achieved and the blood pressure
and heart rate responses. While of great value in many cases, however, this test may provide
equivocal or misleading information in some. Alternative investigations are needed when the diagnosis
remains uncertain or functional assessment is inadequate, especially when there are electrocardiographic
features which are difficult or impossible to interpret. Myocardial perfusion imaging and stress
echocardiography are of particular value in demonstrating the extent and localisation of myocardial
ischaemia. Echocardiography and radionuclide angiography are helpful in evaluating ventricular
function.
(4) The interpretation of chest pain is particularly difficult in young and middle-aged women. The
classical symptom complex of chronic stable angina, which is a reliable indicator of myocardial
ischaemia in men is not so in younger women. This problem is compounded by the relatively high
prevalence of ‘syndrome X’ in women, and by the frequency of ‘false positive’ exercise tests.
(5) The general management of the patient is of paramount importance. This must include a strategy
tailored to personal circumstances, an explanation of the nature of the condition and its treatment,
and attention to lifestyle issues. Aspirin should be administered unless contra-indicated, and lipidlowering
drugs should be considered if dietary measures fail to reduce total serum cholesterol
below 5·0 mmol . l"1.
(6) Nitrates, â-blockers and calcium antagonists, alone or in combination, are effective in controlling the
symptoms of angina in most cases. Because there is considerable variation in the response of patients to
each class of drug, and the side-effects are unpredictable, the choice of agent should be determined
on an individual basis. â-blockers are particularly indicated in those who experience angina after a
myocardial infarction as they reduce the risk of reinfarction and death. The costs of the various
drug regimens needs to be taken into account.
(7) Coronary angiography should be undertaken when symptoms are not satisfactorily controlled by medical
means, when non-invasive investigations suggest that the prognosis could be improved by
angioplasty or coronary artery bypass surgery, and when it is considered essential to establish the
diagnosis.
(8) Percutaneous transluminal coronary angioplasty (PTCA) is an effective treatment for stable angina
pectoris, and is indicated for patients with angina not satisfactorily controlled by medical treatment
when there are anatomically suitable lesions. Restenosis continues to be a problem, which is diminished
but not abolished by stenting. There is, as yet, no evidence that PTCA reduces the risk of death.
Guidelines on management of stable angina pectoris 409 Eur Heart J, Vol. 18, March 1997
(9) Coronary bypass graft surgery is highly effective in relieving the symptoms of stable angina and reduces
the risk of death over the succeeding 10 years in particular subgroups of patients, such as those
with left main stenosis, and three vessel disease, escpecially if left ventricular function is impaired.
(10) There is evidence that there are large numbers of patients in the community who are not being
appropriately assessed and treated. Specifically, many of those with stable angina have never undergone
functional testing to confirm the diagnosis and determine prognosis. Furthermore, neither
lipid-lowering agents nor aspirin are being as widely prescribed as they should be.
(11) Because of the wide variations in the quality of care afforded to sufferers from angina, there is a strong
case for auditing several components of the management of the condition. As is the practice in some
countries, local, regional or national registers of the outcome of PTCA and surgery should be created
and maintained.
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Appendix
Procedure of the Task Force
The Task Force on the Management of Stable Angina
Pectoris was created by the Committee for Scientific
and Clinical Initiatives of the European Society of
Cardiology in September 1995 and asked to report to
the Congress of the Society in August 1996.
The members of the Task Force were Prof. D. G.
Julian (Chairman) U.K., Prof. M. E. Bertrand (France),
Prof. Å. Hjalmarson (Sweden), Dr K. Fox (U.K.),
Prof. M. L. Simoons (The Netherlands), Prof. L.
Ceremuzynski (Poland), Prof. A. Maseri (Italy), Prof. T.
Meinertz (Germany), Prof. J. Meyer (Germany), Prof.
K. Pyörälä (Finland), Ass. Prof. N. Rehnqvist (Sweden),
Prof. L. Tavazzi (Italy), Prof. P. Toutouzas (Greece),
Prof. T. Treasure (U.K.)
A Core Group consisting of D. G. Julian, M. E.
Bertrand, Å. Hjalmarson, K. Fox and M. L. Simoons
prepared an initial document which was circulated to the
Task Force. The document was then extensively revised
and circulated to the members of the Committee for
Scientific and Clinical Initiatives and to the following
Working Groups:
Cardiac Rehabilitation and Exercise Testing
Drug Therapy in Cardiology
Myocardial Function
Nuclear Cardiology and Magnetic Resonance
Microcirculation
Echocardiography
Coronary Circulation
Epidemiology and Prevention
Thrombosis and Platelets
Pathogenesis of Atherosclerosis
Cardiovascular Surgery
Heart Failure
After further revision, it was submitted for
approval to the Committee for Scientific and Clinical
Initiatives of the Society. It was also sent to Dr F. L.
Ritchie of Seattle and Dr B. Gersch of Washington who
kindly commented on it. The report was finalised for
publication in November 1996.
The Task Force wishes to thank Mrs W. Thieme
for her invaluable assistance.
Financial Support
The Task Force wishes to express its appreciation of
the financial support provided by Astra Hässle AB,
Behringwerke AG, Institut de Recherches Internationales
Servier, Knoll AG, Laboratoires Searle,
Merck, Sharp and Dohme, Pfizer Ltd and Synthélabo.
The Task Force report was developed without any
involvement of the pharmaceutical companies that
provided financial support.
Guidelines on management of stable angina pectoris 413
Eur Heart J, Vol. 18, March 1997
