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Management of stable angina 

Management of stable angina

Chapter:
Management of stable angina
Author(s):

Adam D. Timmis

DOI:
10.1093/med/9780199204854.003.161304_update_002

Update:

The use of the Syntax scoring system which characterizes the complexity of coronary artery lesions at angiography now helps to identify patients who are best treated with CABG rather than PCI. A high syntax score is associated with a better long term outcome from CABG compared to PCI. This chapter now includes content from retired Chapter 16.13.8.

Updated on 29 Oct 2015. The previous version of this content can be found here.
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Essentials

Angina—the pain provoked by myocardial ischaemia—is usually caused by obstructive coronary artery disease that is sufficiently severe to restrict oxygen delivery to the cardiac myocytes. Quality of life is impaired in direct proportion to the severity of symptoms.

Clinical history remains the most useful basis for diagnosis and referral decisions to specialist services, the commonest indications being (1) new-onset angina, (2) exclusion of angina in high-risk individuals with atypical symptoms, (3) worsening angina in a patient with previously stable symptoms, (4) new or recurrent angina in a patient with history of myocardial infarction or coronary revascularization, (5) assessment of occupational fitness (e.g. airline pilots).

Investigation—noninvasive testing is used primarily for diagnosis, but whatever test is employed—exercise ECG, myocardial perfusion imaging, stress echocardiography, or multidetector CT—the incremental diagnostic value is greatest for patients with an intermediate pretest probability of coronary artery disease in whom uncertainty is greatest. Such tests also have a role in risk assessment to inform decisions about the urgency and aggressiveness of treatment in individual cases.

Medical treatment of angina involves (1) dealing with exacerbating comorbidities, (2) secondary prevention by lifestyle modification (smoking cessation, exercise training, Mediterranean-style diet, etc.) and drugs (aspirin, statins, etc.), (3) antianginal drugs (most commonly β‎-blockers, calcium channel blockers, and short-acting nitrates).

Patients with continuing moderate or severe stable angina despite optimal medical treatment should undergo coronary angiography, particularly if they are identified as being at high risk on noninvasive testing. In symptomatic patients, revascularization is generally indicated if one or more of the major coronary arteries—or their large branches—have flow-limiting stenoses (>70% luminal narrowing) or occlusions. Percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) produce comparable symptomatic benefit. With regard to life expectancy, PCI does not produce survival benefit in patients with stable angina. By contrast, studies more than 40 years ago showed that CABG produced small gains in life expectancy in some patients.

With current management strategies, patients with angina are living longer, but a few remain symptomatic with poor quality of life despite optimal medical treatment and having exhausted revascularization options. Psychological support is important to treat anxiety and depression and improve confidence, but other treatment options such as neuromodulatory techniques are not evidence-based and do not have guideline recommendations.

Introduction

Angina—the pain provoked by myocardial ischaemia—is usually caused by obstructive coronary artery disease that is sufficiently severe to restrict oxygen delivery to the cardiac myocytes (Box 16.13.4.1). It is one of the most common initial manifestations of coronary artery disease, occurs almost as commonly in women as in men, and is not showing the steep decline in incidence seen for acute myocardial infarction. When angina occurs in patients without coronary artery disease it may be attributable to other ischaemic mechanisms such as severe anaemia resulting in inadequate oxygen delivery to the cardiac myocytes, or left ventricular hypertrophy secondary to hypertension or aortic stenosis resulting in increased oxygen demand. The appropriately named syndrome X is a diagnosis of exclusion in patients with angina and unobstructed coronary arteries for which there is no clear cause despite full cardiac investigation: abnormal microvascular function is one proposed mechanism, but although symptoms are often resistant to treatment, prognosis is usually good in terms of life expectancy.

In most patients with angina caused by coronary artery disease, quality of life is impaired in direct proportion to the severity of symptoms (Fig. 16.13.4.1). Prognosis is often good, particularly in patients with chronic stable symptoms receiving contemporary secondary prevention therapy, but in those with recently diagnosed angina risk is greater, with a 2 to 3% incidence of death or nonfatal myocardial infarction in the first year. Recognition of the need for early investigation has led to the widespread implementation of chest pain clinics in the United Kingdom and elsewhere to provide patients with suspected angina prompt treatment to relieve symptoms and reduce risk.

Fig. 16.13.4.1 Effect of angina on quality of life. Data are at baseline and 2 years after randomization in the RITA trial, showing impact of angina on life aspects encoded in part 2 of the Nottingham Health Profile. Note how quality of life deteriorates rapidly with worsening angina.

Fig. 16.13.4.1
Effect of angina on quality of life. Data are at baseline and 2 years after randomization in the RITA trial, showing impact of angina on life aspects encoded in part 2 of the Nottingham Health Profile. Note how quality of life deteriorates rapidly with worsening angina.

Pocock SJ, Henderson RA, Seed P, Treasure T, Hampton JR. Quality of life, employment status, and anginal symptoms after coronary angioplasty or bypass surgery.3-year follow-up in the Randomized Intervention Treatment of Angina (RITA) Trial. Circulation 1996;94:135–42.

Referral for specialist assessment

Referral for specialist assessment (Box 16.13.4.2) is indicated in all patients with known coronary artery disease—particularly those with previous myocardial infarction or coronary revascularization—who experience abrupt worsening of symptoms, often indicating plaque rupture and risk of impending infarction.

However, referral decisions may be more difficult in patients presenting for the first time with chest pain. A noncardiac diagnosis accounts for most cases, but it is the task of the primary care or general physician to ensure that all those with suspected angina receive specialist assessment for confirmation of the diagnosis and risk stratification to identify those at greatest risk who need more intensive treatment. As in any screening process, false-negative diagnoses in which patients receive inappropriate reassurance must be avoided. By contrast, a proportion of false-positive diagnoses and referrals is acceptable, and among patients referred from primary care to chest pain clinics 75% have a noncardiac diagnosis.

In primary care, screening is based largely on the character of the symptoms and the age and gender of the patient, other risk factors further helping to identify those with a high probability of coronary artery disease (see below). Access to noninvasive diagnostic tests can be helpful in primary care or the nonspecialist clinic, but there is often insufficient recognition of their limitations, the exercise ECG (for example) having a diagnostic sensitivity of only about 68%, which means that up to one-third of all cases with coronary disease are missed. For this reason, the clinical history remains the most useful basis for diagnosis and referral decisions. Thresholds for referral should be lowered in high-risk patients, including those with previous myocardial infarction and diabetes, and also in airline pilots and public service drivers whose occupations might put others at risk in the event of myocardial infarction or sudden death.

The recommendation that all patients with suspected angina be referred for specialist assessment leaves little room for prevarication. Yet studies repeatedly show inequitable management of patients with chest pain, those with the greatest need often being the very patients who receive the least intensive treatment. Thus elderly patients with chest pain and those of South Asian origin are both high-risk groups, but are less likely than their younger and white counterparts to receive referral to chest pain clinics. Women are also disadvantaged and are less likely than men to be referred, even though it is increasingly recognized that angina in women is almost as common as in men and prognosis little better (Fig. 16.13.4.2). The reasons for this inequity are complex and poorly understood, but the consequences for health care are important.

Fig. 16.13.4.2 Prognosis of angina in women and men. Primary care electronic records for Finland linked with mortality data have permitted estimation of the prognosis of angina for men and women, presented here as standardized mortality ratios. Two mutually exclusive case definitions of angina were used based on nitrate prescription and test positivity, yielding respectively over 90 000 and over 27 000 cases. The data show that the contemporary prognosis of angina is not always good and at all ages is similar for men and for women. SMR, standardized mortality ratio.

Fig. 16.13.4.2
Prognosis of angina in women and men. Primary care electronic records for Finland linked with mortality data have permitted estimation of the prognosis of angina for men and women, presented here as standardized mortality ratios. Two mutually exclusive case definitions of angina were used based on nitrate prescription and test positivity, yielding respectively over 90 000 and over 27 000 cases. The data show that the contemporary prognosis of angina is not always good and at all ages is similar for men and for women. SMR, standardized mortality ratio.

Hemingway H, McCallum A, Shipley M, Manderbacks K, Martikainen P, Keskimaki I. Incidence and prognostic implications of stable angina pectoris among women and men. JAMA, 2006;295:1404–11.

Diagnosis of angina

Angina varies considerably in its clinical presentation and its overlap with other entities can make the differential diagnosis of chest pain difficult. A detailed description of the symptom complex is the most important step in the diagnostic process and in the context of other factors, particularly age and gender, allows the clinician to estimate the probability of coronary artery disease. The extent of work-up required to exclude a noncardiac cause needs to be individually determined. The diagnosis is informed by the clinician’s intuition, experience, and interviewing skills, supported by investigations such as resting ECG, stress testing, and coronary angiography.

Clinical evaluation

A careful history of the character, location, radiation, provocation, and duration of the chest pain provides the most useful diagnostic information. Typically angina is experienced as a constricting, centrally located chest discomfort, radiating to the arms, throat, or jaw, provoked by exertion, less commonly by stress, and relieved by rest usually within 5–10 min. Symptoms are often worse in the morning, shortly after getting up, probably because catecholamine levels and blood pressure peak at this time of day. For similar reasons angina tends to be worse in cold weather and also after a heavy meal. In addition to age and gender, diagnostic probability is also influenced by a family history of premature coronary artery disease and also by other risk factors—particularly diabetes, smoking, hypertension, and dyslipidaemia. Thus, in the patient with chest pain, the probability of coronary disease is very low in men and women under 30, almost regardless of the typicality of the symptoms, while in men and women over 60 with multiple risk factors the probability of coronary disease is high even when the history has atypical features. The experienced clinician makes these probability judgements intuitively in the consulting room and they provide the main basis for the diagnosis of angina. For further discussion see Chapter 16.2.1.

Despite the reliance on clinical history in making a diagnosis of angina, it can be misleading, with atypical features, such as exertional dyspnoea in the absence of chest pain. Atypical presentations are said to be more common in patients with diabetes but, contrary to popular belief, there is little evidence that this also applies in women and South Asian people.

The physical examination is often normal in the patient with angina but may contribute to diagnosis if signs of major risk factors are identified, particularly hypertension, cutaneous manifestations of dyslipidaemia, and complications of diabetes such as retinopathy and neuropathy. Patients with signs of peripheral vascular disease (e.g. absent pulses, arterial bruits) have associated coronary involvement in most cases.

Simple laboratory investigations may also contribute to diagnosis by identifying groups at heightened risk of coronary disease due to renal dysfunction, dyslipidaemia, or diabetes. Anaemia is also important to document because it may cause or—more commonly—exacerbate myocardial ischaemia.

Noninvasive investigation

Noninvasive testing is used primarily for diagnosis of coronary artery disease, but also has a role in risk assessment (see below). By tradition, nearly all patients presenting with chest pain have an ECG, although it is of limited diagnostic value. Many patients with angina have a normal recording and, although regional ST-segment or T-wave changes are commonly associated with coronary disease, only pathological Q waves, reflecting previous myocardial infarction, are diagnostic. Other features of the ECG of potential relevance include tachycardia—particularly in patients with atrial fibrillation—and evidence of left ventricular hypertrophy, either of which may cause or exacerbate myocardial ischaemia.

Diagnostic indications for noninvasive testing depend largely on the level of uncertainty following the clinical assessment. Thus, a 60-year-old man with multiple risk factors who experiences constricting chest pain relieved by rest when he walks up stairs does not need noninvasive testing for diagnostic purposes—he clearly has angina and a negative test would do nothing to change that diagnosis. Similarly, a 25-year-old with transient stabbing pains in the left side of the chest unrelated to exertion does not have angina and a positive test would not modify that diagnostic judgement. These Bayesian considerations apply to all noninvasive tests that commonly provide false-positive or false-negative results with little incremental value when the probability of coronary disease based on clinical assessment is respectively very low or very high. Incremental diagnostic value is greatest for patients with an intermediate pretest probability of coronary artery disease (say 10–90%) in whom uncertainty is greatest (Fig. 16.13.4.3). In these patients the results of noninvasive testing, positive or negative, can help resolve the uncertainty and contribute to the appropriate further management (Fig. 16.13.4.4). The choice of noninvasive test is driven in part by the probability of coronary disease, a low probability (say 10–30%) favouring a test with very high sensitivity such as CT calcium scoring and angiography, which allows confident rule-out of coronary artery disease if the test is normal. By contrast, when the probability of coronary artery disease is higher, perfusion imaging or stress echo are favoured over the exercise ECG because the specificity of these imaging techniques is higher and an abnormal result strongly suggestive of coronary artery disease. When the probability of coronary disease is very high (>60%) the United Kingdom NICE guidance is for coronary angiography without prior noninvasive testing. However, other contemporary guidelines consider noninvasive ischaemia testing a necessary prerequisite to coronary angiography in the diagnostic work-up of these patients.

Fig. 16.13.4.3 Diagnosis of coronary artery disease—(CAD)—probability analysis. If the pretest probability of CAD is very low (e.g. a young patient with very atypical chest pain) or very high (e.g. an elderly patient with typical angina), stress testing is generally unhelpful for diagnostic purposes because a positive test does not increase the probability of CAD very much. By contrast, in patients with an intermediate probability of disease, where there is real uncertainty about the diagnosis, a positive test produces a much larger increase in the probability of disease.

Fig. 16.13.4.3
Diagnosis of coronary artery disease—(CAD)—probability analysis. If the pretest probability of CAD is very low (e.g. a young patient with very atypical chest pain) or very high (e.g. an elderly patient with typical angina), stress testing is generally unhelpful for diagnostic purposes because a positive test does not increase the probability of CAD very much. By contrast, in patients with an intermediate probability of disease, where there is real uncertainty about the diagnosis, a positive test produces a much larger increase in the probability of disease.

Fig. 16.13.4.4 Risk-based management strategy in chronic stable angina.

Fig. 16.13.4.4
Risk-based management strategy in chronic stable angina.

Timmis AD, Nathan AW, Sullivan ID. Essentials of cardiology, 3rd edition. Oxford, Blackwell Scientific Publications, 1997.

Exercise ECG

Once widely used for diagnosis of coronary artery disease, it is now giving way to the newer generation of noninvasive diagnostic tests described below. Details are described in Chapter 16.3.1. The sensitivity and specificity of the exercise ECG is 68% and 77% respectively, with diagnostic value tending to be lower in women than in men. The regional development of planar or down-sloping ST-segment depression, with gradual recovery when exercise stops, is usually diagnostic, particularly when associated with typical chest pain (Fig. 16.13.4.5a). The exercise ECG may also provide prognostic information: low exercise tolerance, ST depression early during exercise, an exertional fall in blood pressure, or exercise-induced ventricular arrhythmias all point to an increased risk of myocardial infarction or sudden death. The Duke treadmill score, which takes into account duration of exercise, degree of ST-segment deviation, and angina provides a quantitative prognostic assessment and a useful basis for determining the urgency of coronary arteriography.

Fig. 16.13.4.5 Noninvasive testing for diagnosis of myocardial ischaemia. (a) Exercise ECG: lead V2 of the ECG is shown. Exercise produces progressive ST-segment depression with gradual resolution during the recovery period. (b) Isotope perfusion imaging. These are colour-coded perfusion images obtained during exercise stress. The upper panels shows reversible ischaemia with an exertional perfusion defect (arrowed) affecting the lateral left ventricular wall with resolution at rest. The lower panels show fixed perfusion defects denoting prior infarction.

Fig. 16.13.4.5
Noninvasive testing for diagnosis of myocardial ischaemia. (a) Exercise ECG: lead V2 of the ECG is shown. Exercise produces progressive ST-segment depression with gradual resolution during the recovery period. (b) Isotope perfusion imaging. These are colour-coded perfusion images obtained during exercise stress. The upper panels shows reversible ischaemia with an exertional perfusion defect (arrowed) affecting the lateral left ventricular wall with resolution at rest. The lower panels show fixed perfusion defects denoting prior infarction.

Isotope perfusion imaging

This is also widely used for diagnostic purposes in patients with an intermediate probability of coronary artery disease and, although more costly and time-consuming than the exercise ECG, has enhanced diagnostic accuracy (sensitivity and specificity about 90%). Details are described in Chapter 16.3.3. Fixed defects, present at rest and during stress, indicate areas of myocardial infarction (Fig. 16.13.4.5b). Isotope perfusion imaging also provides useful prognostic information, the extent and severity of perfusion defects (fixed or reversible), the degree of lung uptake of radio-isotope (reflecting level of pulmonary capillary pressure), and the calculated ventricular volume and ejection fraction all predicting risk of future events.

Cardiac magnetic resonance (CMR) perfusion imaging

This has now found an important role in the investigation of patients with an intermediate probability of coronary artery disease, offering high levels of diagnostic accuracy (sensitivity c.90%, specificity 80%) for detection of myocardial ischaemia. Although currently unable to provide the same coronary anatomical definition as CT or conventional angiography, it also provides additional prognostic information about ventricular volumes, ejection fraction, and the extent of myocardial infarction which combine to predict risk of future events. The identification of viable and hibernating myocardium with CMR may be used to guide revascularization strategies.

Stress echocardiography

This too is used increasingly for diagnostic purposes in patients with an intermediate probability of coronary artery disease, but is more dependent than other noninvasive tests on the technical and interpretive skills of the operator. Details are described in Chapter 16.3.2. In expert hands it has similar sensitivity to exercise ECG but higher specificity for diagnosing coronary artery disease in patients with suspected angina. Left ventricular imaging during dobutamine infusion permits assessment of regional wall motion in response to adrenergic stress, with decreasing systolic wall motion or wall thickening indicating ischaemia and the likelihood of coronary artery disease.

Multidetector CT (MDCT)

The current generation of multidetector (or multislice) CT scanners have sufficient image acquisition speed and spatial resolution to provide noninvasive coronary arteriograms that are finding increasing clinical application particularly for exclusion of coronary artery disease based on very high levels of diagnostic sensitivity that exceed 95%. (Fig. 16.13.4.6). Details are described in Chapter 16.3.3. Unlike conventional coronary arteriography information is also provided about the arterial wall, particularly the severity and distribution of coronary calcification which relates to the severity of coronary atherosclerosis. MDCT provides real promise for delivery of noninvasive coronary arteriography whichis already having a significant impact on the outpatient assessment of patients with chest pain, particularly as a rule-out test in those with a low probability of coronary disease.

Fig. 16.13.4.6 Noninvasive coronary angiography by MDCT. The right coronary artery (arrowed) is patent but has localized areas of dense calcification in its proximal and mid segments denoting atherosclerosis.

Fig. 16.13.4.6
Noninvasive coronary angiography by MDCT. The right coronary artery (arrowed) is patent but has localized areas of dense calcification in its proximal and mid segments denoting atherosclerosis.

Risk assessment of angina

Recent clinical trials of patients with chronic angina show that aggressive treatment under cardiological supervision reduces risk considerably such that long-term prognosis is good, with all-cause mortality rates of about 1.5% per year. However, prognosis is worse in cohorts attending chest pain clinics in the early weeks or months after symptom onset, with mortality rates in excess of 3% in the first year. Identification of high-risk patients is therefore an important part of the initial assessment to inform decisions about the urgency and aggressiveness of treatment in individual cases.

Clinical indicators of risk

As with diagnosis, it is the clinical assessment that provides the most useful prognostic information in angina. Risk is greatest in patients who are old, those with typical symptoms and—contrary to conventional wisdom—those with more severe symptoms. Women and South Asians with angina do not appear to be at greater risk. Risk increases with the number of ‘reversible’ risk factors, particularly diabetes, smoking, hypertension, and dyslipidaemia, all of which are important targets for treatment. Risk is also increased in patients with a history of myocardial infarction or stroke. Tachycardia is associated with increased risk, although treatment to slow the heart rate is directed primarily at preventing exertional ischaemia. Heart failure increases risk substantially. The most useful laboratory markers of risk are blood concentrations of lipids (particularly LDL cholesterol and apolipoproteins), glycated haemoglobin, and creatinine, but the search is on for novel biomarkers to identify high-risk stable angina patients with greater precision.

Noninvasive testing for risk assessment

Abnormalities of the resting ECG, particularly pathological Q waves and left bundle branch block, are associated with heightened risk in the patient with angina. Other noninvasive tests, including the exercise ECG and perfusion imaging, are also used for risk assessment (see ‘Diagnosis of angina’ earlier). Generally speaking, negative test results indicate a good prognosis and a low level of urgency for further invasive investigation. However, when test results suggest severe and extensive ischaemia, risk is often high with important implications for future management.

Risk scores

Many scores have been developed for determining cardiovascular risk in healthy populations and in patients with acute myocardial infarction. Scores are also available for risk assessment in chronic stable angina based on many of the clinical and laboratory variables described above, plus echocardiographic measurement of left ventricular function. As yet, angina risk scores have not found major application in clinical practice.

Invasive testing for risk assessment

In patients with angina, risk of myocardial infarction and cardiovascular death is related to the extent and severity of angiographic coronary artery disease. Risk is particularly high when disease (luminal stenosis >50%) affects all three of the major coronary arteries. In patients with left main coronary artery disease death is inevitable in the event of left main occlusion and urgent revascularization is usually recommended.

Novel biomarkers

A range of inflammatory markers, including C-reactive protein, have been assessed in stable patients with coronary artery disease, but their incremental predictive value for future coronary events is very low once conventional risk factors have been taken into account. Brain natriuretic peptide may be more useful in this group of patients, although currently its main clinical application is in the diagnosis of heart failure (see Chapter 16.2.1).

Treatment of angina

The purpose of treatment is to correct symptoms and reduce risk, thereby improving both the quality of life and its duration (Fig. 16.13.4.7).

Fig. 16.13.4.7 Medical management of stable angina.

Fig. 16.13.4.7
Medical management of stable angina.

European Society of Cardiology guidelines. Eur Heart J 2006;27:1341–81. With permission of Oxford University Press (UK) � European Society of Cardiology, www.escardio.org/guidelines.

General measures

Comorbidities that exacerbate angina include anaemia, obesity, and thyrotoxicosis, all of which need treating. Most important, however, is hypertension, which increases myocardial oxygen demand in proportion to its severity. Simple lowering of blood pressure will often correct angina without the need for additional symptomatic treatment. Atrial fibrillation is also important because it is common, particularly in elderly patients, and increases myocardial oxygen demand due to tachycardia. Symptom relief can often be achieved by heart rate control or cardioversion. Aortic stenosis is another cause of angina that can be corrected by valve replacement.

Secondary prevention

The risk of myocardial infarction, stroke, and cardiovascular death can be reduced by lifestyle modification and specific drug therapy. Logic also requires that major atherogenic risk factors—particularly diabetes, smoking, hypertension, and dyslipidaemia—are treated vigorously in patients with angina, evidence for risk reduction being best for blood pressure control, smoking cessation, and LDL cholesterol reduction. Strict glycaemic control in type 2 diabetes, on the other hand, provides little demonstrable protection against cardiovascular endpoints although microvascular complications (renal failure and retinopathy) are effectively diminished

Lifestyle modification

Evidence-based recommendations are for smoking cessation, exercise training and a Mediterranean-style diet characterized by low intake of total and saturated fats and increased intake of fresh fruits and vegetables, and cereals rich in fibre, antioxidants, minerals, vegetable proteins, and B-group vitamins. Weight reduction in obese patients is also recommended, particularly those with hypertension, dyslipidaemia, or diabetes.

Secondary prevention drugs

All patients with angina should receive aspirin 75–150 mg daily, its antiplatelet activity reducing the thrombotic response to plaque rupture and protecting against myocardial infarction and stroke. Patients intolerant of aspirin despite proton pump inhibition should be treated with clopidogrel, which offers equivalent protection.

Patients with angina should also receive statin therapy to lower LDL cholesterol, thereby reducing lipid accumulation in the arterial wall and stabilizing the atherosclerotic plaque against rupture. Risk reduction is independent of baseline LDL cholesterol concentration, but the more it is lowered the greater the protection against cardiovascular events. At present, therefore, recommendations are to treat to a target of 4 mmol/litre for total cholesterol and 2 mmol/litre for LDL cholesterol. If this cannot be achieved with simvastatin 40 mg (the conventional first-line statin in the United Kingdom), the dose needs increasing or a more potent statin such as atorvastatin or rosuvastatin needs to be substituted. In patients who cannot be treated to target or who are unable to tolerate statins, ezetimibe is usually added (or substituted) to reduce cholesterol absorption from the bowel, although there is no current evidence of prognostic benefit. The cardiovascular risk associated with low HDL is well established, but treatment to increase HDL with nicotinic acid derivatives or the more potent cholesteryl ester transfer protein (CETP) inhibitors that are currently under investigation, does nothing to reduce risk in patients with coronary artery disease.

Angiotensin converting enzyme (ACE) inhibition provides some additional protection against cardiovascular endpoints in patients with angina, but this probably relates to their blood pressure lowering effect and current recommendations are for their use only in patients with angina who have additional indications for ACE inhibition such as hypertension, heart failure, or diabetes.

β‎-Blockers, though widely used for symptomatic treatment, have no clear evidence-based indication for secondary prevention in patients with angina unless there is associated left ventricular dysfunction, when prognostic benefit is well established. Antioxidant vitamins C and E and omega-3 fatty acids have failed the test of clinical trials for secondary prevention in coronary artery disease. Similarly, there appears to be no role for hormone replacement therapy for protecting against coronary events in postmenopausal women.

Antianginal drugs

Drugs used to treat angina reduce ischaemia by improving the balance between myocardial oxygen supply and demand (Fig. 16.13.4.8). Guideline recommendations are that medical therapy with antianginal drugs should be tried before angioplasty or surgery is considered, except in those patients with stable angina with left main stem or multivessel coronary disease in whom there is evidence that surgical revascularization might improve prognosis.

Fig. 16.13.4.8 Symptom relief with drugs.

Fig. 16.13.4.8
Symptom relief with drugs.

The antianginal drugs recommended for initial treatment are β‎-blockers and calcium channel blocker, together with a short-acting nitrate for prompt alleviation of angina attacks. If these drugs are not tolerated, are contraindicated, or fail to correct symptoms, alternative antianginals may be considered.

β‎-Blockers

These drugs reduce myocardial oxygen demand, principally by slowing the heart rate, although reductions in left ventricular wall tension (blood pressure) and contractility also contribute. Choice of β‎-blocker is largely determined by patient acceptability, with preference given to once-daily cardioselective agents such as bisoprolol. Effective relief of exertional angina can often be obtained without recourse to other drugs if the heart rate response to exercise can be reduced sufficiently. There is a clear indication for β‎-blockers when angina occurs in patients with heart failure or asymptomatic left ventricular dysfunction. They are usually well tolerated, but noncardiac side effects, particularly fatigue and erectile dysfunction, may be troublesome even with cardioselective agents. β‎-Blockers are contraindicated in patients with bronchial asthma.

Calcium blockers

Like nitrates, these are vasodilators and improve myocardial oxygen balance by their effect on coronary flow and peripheral resistance. Angina complicated by hypertension provides a clear indication for drugs of this class, and amlodipine is usually the preferred agent. Diltiazem and verapamil are also useful because, in addition to vasodilator activity, they often produce minor reductions in heart rate, although combination therapy with β‎-blockers is best avoided. Nifedipine, which tends to increase heart rate, is not recommended for treatment of angina. Side effects of calcium blockers are related to vasodilatation and include facial flushing, postural dizziness, and mild ankle oedema.

Nitrates

These drugs improve myocardial oxygen delivery and reduce demand by direct coronary and peripheral vascular dilatation. Sublingual glyceryl trinitrate by tablet or spray should be given to all patients with angina, rapid absorption through the buccal mucosa providing symptomatic relief within 3 min. It can also be used prophylactically to prevent angina during exertion. Long-acting isosorbide mononitrate for regular oral administration is widely used, although variable tolerance to its therapeutic action may occur. Side effects are rarely troublesome apart from headache during the first few days of treatment.

Potassium channel openers

Nicorandil is the only drug in this group licensed to treat angina. It is a vasodilator with effects comparable to those of long-acting nitrates. The principal side effect is headache.

Trimetazidine

This interesting compound is licensed for treatment of angina in a number of European countries (not the United Kingdom). Its pharmacological effects are metabolic, not haemodynamic, with coupling between glycolysis and carbohydrate oxygenation restored by shifting cardiac energy metabolism from oxygenation of fatty acids (the preferred myocardial substrate) to glucose, thus preserving intracellular ATP levels. Antianginal effects are comparable to other agents. Side effects, including gastrointestinal disturbance, are rarely troublesome.

Ivabridine

Ivabridine inhibits the If channel in the sinus node, reducing the slope of diastolic depolarization and slowing the heart rate. The effect of ivabridine on heart rate is comparable to that of β‎-blockers, but because If channels are largely restricted to the heart and the retina blood pressure is unaffected and many of the noncardiac effects of β‎-blockers, particularly fatigue and erectile dysfunction, do not occur. Mild visual side effects tend to resolve during treatment. Antianginal efficacy appears to be comparable to β‎-blockers and calcium blockers and the drug is now licensed for treatment of angina in patients with normal sinus rhythm (rate reduction does not occur in atrial fibrillation) who have a contraindication to or intolerance of β‎-blockers.

Ranolazine

Ranolazine’s mechanism of action appears to involve inhibition of the late inward sodium channel which indirectly prevents calcium overload of ischaemic myocytes and reduces diastolic wall tension and oxygen demand. Heart rate or blood pressure are unaffected. Antianginal effects are additive to those of β‎-blockers and calcium blockers. Side effects including constipation and dizziness are rarely troublesome.

Revascularization

In the patient with angina, revascularization provides a nonpharmacological means of improving myocardial oxygen delivery by restoring coronary flow to the ischaemic myocardium. More than 60% of all revascularization procedures in stable angina are now by percutaneous intervention (PCI) using balloon angioplasty and stenting (Fig. 16.13.4.9). The remainder are by coronary artery bypass surgery (CABG), the choice depending largely on the extent and severity of coronary artery disease. At present, this can only be determined by coronary angiography which is an essential prerequisite of revascularization in the management of angina. See Chapters 16.13.6 and 16.13.7 for further discussion.

Fig. 16.13.4.9 Coronary stenting. Right coronary arteriogram (a) before stenting and (b) after deployment of a drug-eluting stent across the diseased segment (arrowed) in the proximal part of the vessel. The patient had stable angina and experienced complete relief of symptoms after the procedure.

Fig. 16.13.4.9
Coronary stenting. Right coronary arteriogram (a) before stenting and (b) after deployment of a drug-eluting stent across the diseased segment (arrowed) in the proximal part of the vessel. The patient had stable angina and experienced complete relief of symptoms after the procedure.

Which patients with stable angina should undergo coronary angiography?

Guideline recommendations are for angiography in patients with continuing moderate or severe angina despite optimal medical treatment. Other groups for whom angiography is recommended include those who have been successfully resuscitated from sudden cardiac death or who have life-threatening ventricular arrhythmias and those with suspected or known coronary artery disease whose jobs (e.g. piloting aircraft, driving public service vehicles) are dependent on a normal or fully revascularized coronary circulation. It may also be indicated in patients unwilling or unable to take antianginal drugs, or those in whom there is important diagnostic uncertainty despite noninvasive investigation. In patients whose angina has responded satisfactorily to medical treatment there is no absolute requirement for angiography but the potential for small gains in life expectancy with CABG for high-risk coronary anatomy (left main or three-vessel disease) should be discussed, and angiography offered to those who wish to have the coronary anatomy defined.

Choice of revascularization procedure—CABG vs PCI

In symptomatic patients who have undergone cardiac catheterization, revascularization is generally indicated if one or more of the major coronary arteries—or their large branches—have flow-limiting stenoses (>70% luminal narrowing) or occlusions. The choice of revascularization procedure is dependent on a range of factors and should be discussed in a multidisciplinary group that includes cardiologists and cardiac surgeons:

  • Management of stable angina Coronary anatomy—historically, PCI has been preferred for single-vessel and two-vessel coronary artery disease and CABG for more extensive disease. This preference based largely on presumed prognostic benefit for CABG in patients with three-vessel or left main stem disease (see below), has now given way to procedure selection based on coronary scoring systems. Most widely used is the SYNTAX score designed to quantify the complexity of left main or three-vessel disease according to simple lesion criteria readily accessible from the coronary arteriogram. If the SYNTAX score is <22, signifying low lesion complexity, 5-year outcomes favour revascularization by PCI, regardless of the number of diseased vessels. If, on the other hand, the SYNTAX score is higher CABG should be considered and for scores >33, signifying severe lesion complexity, CABG produces unequivocally better 5-year outcomes compared with PCI. In making revascularization decisions however other factors are also important, particularly patient preference.

  • Patient preference—PCI is often preferred because it avoids surgery, requires no more than 48 h hospitalization (day-case PCI is now feasible) and permits early return to normal activities within a few days of the procedure. In expressing a preference, however, it is important that the patient is properly informed of the relative risks and benefits of PCI and CABG in his or her particular case.

  • Procedural risk—mortality is lower for PCI than CABG (0.9% vs 2.2%). Stroke risk may also lower but rates of nonfatal myocardial infarction are comparable.

  • Symptomatic benefit—this is comparable for PCI and CABG, but recurrence of symptoms and need for repeat revascularization is higher for PCI because of coronary restenosis in the months following a successful procedure. Indeed restenosis has been the Achilles heel of PCI, and until the introduction of coronary stents affected 30% or more of all patients. Since then stenting has become widespread, producing more effective coronary patency although reductions in rates of restenosis to less than 10% had to await the introduction of drug-eluting stents that deliver antiproliferative drugs (e.g. sirolimus, paclitaxel) locally within the coronary artery. The prospect of providing long-term relief of symptoms without the need for repeat procedures has considerably enhanced the clinical value of PCI.

  • Prognostic benefit—There have been no studies showing survival benefit for PCI in patients with stable angina. For CABG, small gains in life expectancy have been reported in patients with left main stem coronary disease and three-vessel disease but are from studies nearly 40 years ago and their contemporary relevance may have changed with advances both in surgical techniques and in medical therapy. Indeed it is generally accepted that improvements in the prognosis of coronary artery disease in the last 25 years have little to do with revascularization, but much to do with lifestyle changes and advances in secondary prevention therapy.

Management of refractory angina

With current management strategies patients with angina are living longer, but a proportion, perhaps 5 to 10%, remain symptomatic on optimal medical treatment, having exhausted revascularization options. These patients commonly have extensively collateralized coronary circulations and well-preserved left ventricular function such that prognosis is not worse than other patients with angina, but the quality of life is poor because of refractory symptoms. Psychological support is important to treat anxiety and depression and improve confidence. Other options for further antianginal therapy are not evidence-based and are not recommended in international guidelines. They include neuromodulatory techniques (stellate ganglion block, transcutaneous electrical nerve stimulation, spinal cord stimulation) and enhanced counterpulsation therapy using pressure cuffs applied to the lower limbs that are inflated sequentially during diastole.

Further reading

Sekhri N, et al. (2007). How effective are rapid access chest pain clinics? Prognosis of incident angina and non-cardiac chest pain in 8762 consecutive patients. Heart, 93, 458–63.Find this resource:

Cooper A, et al. (2010). Assessment of recent onset chest pain or discomfort of suspected cardiac origin: summary of NICE guidance. BMJ, 340, c1118. http://guidance.nice.org.uk/CG95/NICEGuidance.Find this resource:

    Timmis A, et al. (2011). Management of stable angina. http://guidance.nice.org.uk/CG126/NICEGuidance.Find this resource:

      Head SJ, et al. (2014). The SYNTAX score and its clinical implications. Heart, 100, 169–77.Find this resource:

        Rapsomaniki E, et al. (2014). Prognostic models for stable coronary artery disease based on electronic health record cohort of 102,023 patients. Eur Heart J, 35, 844–52.Find this resource:

          Boden WE, et al. (2007). Optimal medical therapy with or without PCI in stable coronary disease. N Engl J Med, 35, 1503–16.Find this resource:

            NICE Guideline 2010: Chest Pain of Recent Onset (CG 95). http://www.nice.org.uk/guidance/cg95.Find this resource:

              NICE Guideline 2011: Management of Stable Angina (CG126). http://publications.nice.org.uk/management-of-stable-angina-cg126.Find this resource:

                Montalescot G, et al. (2013). 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J, 34. 2949–3003Find this resource:

                  Fihn SD, et al. (2012). ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol, 60, e44–e164.Find this resource: