Chapter 123: Chronic Stable Angina

ANGINA

Angina pectoris, the most common clinical manifestation of coronary artery disease (CAD), results from an imbalance between myocardial O₂ supply and demand, most often due to atherosclerotic coronary artery obstruction. Other major conditions that upset this balance and result in angina include aortic valve disease (Chap. 116: Valvular Heart Disease), hypertrophic cardiomyopathy (Chap. 117: Cardiomyopathies and Myocarditis and coronary artery spasm (see below).

SYMPTOMS

Angina is typically associated with exertion or emotional upset; relieved quickly by rest or nitroglycerin (Chap. 33: Chest Pain). Major risk factors are cigarette smoking, hypertension, hypercholesterolemia (↑LDL; ↓HDL), diabetes, obesity, and family history of CAD before age 55.

PHYSICAL EXAMINATION

Often normal; arterial bruits or retinal vascular abnormalities suggest generalized atherosclerosis; S₄ is common. During acute anginal episode, other signs may appear: e.g., an S₄, diaphoresis, rales, and a transient murmur of mitral regurgitation due to papillary muscle ischemia.

LABORATORY ECG

May be normal between anginal episodes or show old infarction (Chap. 113: Electrocardiography). During angina, ST- and T-wave abnormalities typically appear (ST-segment depression reflects subendocardial ischemia; ST-segment elevation may reflect acute infarction or transient coronary artery spasm). Ventricular arrhythmias frequently accompany acute ischemia.

STRESS TESTING

Enhances diagnosis of CAD; exercise is performed on treadmill or bicycle until target heart rate is achieved or pt becomes symptomatic (chest pain, light-headedness, hypotension, marked dyspnea, ventricular tachycardia) or develops diagnostic ST-segment changes. Useful information includes duration of exercise achieved; peak heart rate and bp; depth, morphology, and persistence of ST-segment depression; and whether and at which level of exercise pain, hypotension, or ventricular arrhythmias develop. Exercise testing with radionuclide, echocardiographic, or magnetic resonance imaging increases sensitivity and specificity and is particularly useful if baseline ECG abnormalities prevent interpretation of test. Note: Exercise testing should not be performed in pts with acute MI, unstable angina, or severe aortic stenosis. If the pt is unable to exercise, pharmacologic stress with IV dipyridamole, adenosine, regadenoson, or dobutamine can be performed in conjunction with radionuclide or echocardiographic imaging (Table 123-1). Pts with LBBB on baseline ECG should be referred for adenosine or dipyridamole radionuclide imaging, which is most specific for diagnosis of CAD in this setting.

TABLE 123-1: Stress Testing Recommendations
SUBGROUP	RECOMMENDED STUDY
Pt able to exercise
If baseline ST-T on ECG is normal	Standard exercise test (treadmill, bicycle, or arm ergometry)
If baseline ST-T impairs test interpretation (e.g., LVH with strain, digoxin)	Standard exercise test (above) combined with either Perfusion scintigraphy (e.g., ^99mTc-sestamibi) or Echocardiography
Pt not able to exercise (regardless of baseline ST-T abnormality)	Pharmacologic stress test (IV adenosine, regadenoson, dipyridamole, dobutamine) combined with imaging: Perfusion scintigraphy (e.g., ^99mTc-sestamibi or PET [rubidium-82 or N-13 ammonia]) or Echocardiography or Cardiac MRI
LBBB on baseline ECG	Pharmacologic stress test with imaging

The prognostic utility of coronary calcium detection (by electron-beam or multidetector CT) in the diagnosis and management of CAD continues to be defined.

Some pts do not experience chest pain during ischemic episodes with exertion (“silent ischemia”) but are identified by transient ST-T-wave abnormalities during stress (see below).

CORONARY ARTERIOGRAPHY

Major indications are (1) angina refractory to medical therapy, (2) markedly positive exercise test (≥2-mm ST-segment depression, onset of ischemia at low workload, or ventricular tachycardia or hypotension with exercise) suggestive of left main or three-vessel disease, (3) recurrent angina or positive exercise test after MI, (4) to assess for coronary artery spasm, and (5) to evaluate pts with perplexing chest pain in whom noninvasive tests are not diagnostic.

The role of noninvasive coronary imaging techniques (CT and MR angiography) continues to be defined.

Treatment: Chronic Stable Angina

(Fig. 123-1)

GENERAL

Identify and treat risk factors: mandatory cessation of smoking; treatment of diabetes, hypertension, and lipid disorders (Chap. 181: Hypercholesterolemia and Hypertriglyceridemia); advocate a diet low in saturated fat and trans fats.
Correct exacerbating factors contributing to angina: morbid obesity, CHF, anemia, hyperthyroidism.
Reassurance and pt education.

DRUG THERAPY

Sublingual nitroglycerin (TNG 0.3–0.6 mg); may be repeated at 5-min intervals; warn pts of possible headache or light-headedness; teach prophylactic use of TNG prior to activity that regularly evokes angina. If chest pain persists for >10 min despite 2–3 TNG, pt should report promptly to nearest medical facility for evaluation of possible acute coronary syndrome.

Long-Term Angina Suppression

The following classes of drugs are used, frequently in combination.

Long-Acting Nitrates

May be administered by many routes (Table 123-2); start at the lowest dose and frequency to limit tolerance and side effects of headache, light-headedness, tachycardia.

Beta Blockers

All have antianginal properties; β₁-selective agents are less likely to exacerbate airway or peripheral vascular disease (see Table 119-2). Dosage should be titrated to resting heart rate of 50–60 beats/min. Contraindications to beta blockers include CHF, AV block, bronchospasm, “brittle” diabetes. Side effects include fatigue, bronchospasm, depressed LV function, impotence, depression, and masking of hypoglycemia in diabetics.

Calcium Antagonists

Useful for stable and unstable angina, as well coronary vasospasm (see Table 119-2). Combination with other antianginal agents is beneficial, but verapamil should be administered cautiously to pts on beta blockers (additive effects on slowing heart rate). Use sustained-release, not short-acting, calcium antagonists; the latter are associated with increased coronary mortality.

Ranolazine

For pts who continue to experience stable angina despite the above standard medications, consider addition of ranolazine (500–1000 mg PO bid), which reduces anginal frequency and improves exercise capacity without affecting blood pressure or heart rate. Ranolazine is contraindicated in hepatic impairment, in pts with prolongation of the QT_c interval, or in combination with drugs that inhibit its metabolism (e.g., ketoconazole, macrolide antibiotics, HIV protease inhibitors, diltiazem, and verapamil).

Aspirin

81–162 mg/d reduces the incidence of MI in chronic stable angina, following MI, and in asymptomatic men. It is recommended in pts with CAD in the absence of contraindications (GI bleeding or allergy). Consider clopidogrel (75 mg/d) for aspirin-intolerant individuals.

The addition of an ACE inhibitor is recommended in pts with CAD and LV ejection fraction <40%, hypertension, diabetes, or chronic kidney disease.

MECHANICAL REVASCULARIZATION

Used in conjunction with, not as replacement for, risk factor modification and medical therapies.

Percutaneous Coronary Intervention (PCI)

Technique of balloon dilatation, usually with intracoronary stent implantation. Performed on anatomically suitable stenoses of native vessels and bypass grafts; more effective than medical therapy for relief of angina. Has not been shown to reduce risk of MI or death in chronic stable angina; should not be performed on asymptomatic or only mildly symptomatic individuals. With PCI initial relief of angina occurs in 95% of pts; however, restenosis develops in 30–45% following balloon dilatation alone, in ∼20% after bare metal stenting, but in <10% after drug-eluting stent (DES) implantation. Late stent thrombosis may occur rarely in pts with DES; it is diminished by prolonged antiplatelet therapy (aspirin indefinitely and a platelet P2Y12 receptor antagonist for a minimum of 12 months).

Coronary Artery Bypass Graft (CABG)

Appropriately used for angina refractory to medical therapy or when the latter is not tolerated (and when lesions are not amenable to PCI) or if severe CAD is present (e.g., left main, three-vessel disease with impaired LV function). In type 2 diabetics with multivessel CAD, CABG plus optimal medical therapy is superior to medical therapy alone in prevention of major coronary events.

The relative advantages of PCI and CABG are summarized in Table 123-3.

Tables and Figures

FIGURE 123-1

Algorithm for management of ischemic heart disease. ACS, acute coronary syndrome; ASA, aspirin; EF, ejection fraction; IHD, ischemic heart disease; LM, left main.

TABLE 123-2: Examples of Commonly Used Nitrates
	USUAL DOSE	RECOMMENDED DOSING FREQUENCY
Short-acting agents
Sublingual TNG	0.3–0.6 mg	As needed
Aerosol TNG	0.4 mg (1 inhalation)	As needed
Sublingual ISDN	2.5–10 mg	As needed
Long-acting agents
ISDN
Oral	10−40 mg	2−3 times daily
Sustained-action	80−120 mg	1-2 times daily
TNG ointment (2%)	0.5–2	2−3 times daily
TNG transdermal patch	0.2–0.8 mg/h	Apply in morning, remove at bedtime
ISMO
Oral	20–40 mg	2 times daily (once in the A.M., then 7 h later)
Sustained-action	30–240 mg	Once daily

Abbreviations: ISDN, isosorbide dinitrate; ISMO, isosorbide mononitrate; TNG, nitroglycerin.

TABLE 123-3: Comparison of Revascularization Procedures in Multivessel Disease
PROCEDURE	ADVANTAGES	DISADVANTAGES
Percutaneous coronary revascularization	Less invasive Shorter hospital stay Lower initial cost Lower stroke rate	Possible incomplete revascularization May require repeat procedures Limited to specific anatomic subsets
Coronary artery bypass grafting	Lower rate of recurrent angina Ability to achieve complete revascularization	Cost Risk of a repeat procedure due to late graft closure Morbidity and mortality of major surgery

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