Antianginal Drugs

Myocardial oxygen demand rises with three factors: heart rate, the contractile force of the heart muscle, and the tension the ventricular wall must generate to eject blood, called wall stress. When a patient exercises or experiences emotional stress, all three increase together, raising the heart muscle's oxygen requirement.

Myocardial oxygen supply depends on coronary blood flow, which is determined by coronary perfusion pressure, the resistance of the coronary vessels, and the amount of time available for the heart to fill with blood during diastole, since the coronary arteries fill primarily between heartbeats rather than during contraction.

Ischemia results whenever demand exceeds supply. The specific reason demand outpaces supply differs across the three major angina subtypes covered in this module, and that difference determines which drugs are appropriate for each.

At rest, the narrowed artery still delivers enough blood to meet the heart muscle's modest oxygen requirement. During exertion or emotional stress, heart rate, contractility, and wall stress all rise together, increasing oxygen demand beyond what the fixed stenosis can supply. The mismatch produces ischemia and the characteristic chest discomfort of angina.

Because the limiting factor is a fixed anatomic narrowing, stable angina follows a reproducible pattern: a given patient reaches their symptom threshold at roughly the same level of exertion each time, and symptoms resolve predictably within two to five minutes of rest or within one to three minutes of sublingual nitroglycerin.

This classification is a clinical tool for describing symptom severity and tracking response to therapy. A higher class generally indicates a need for more intensive antianginal treatment.

Coronary smooth muscle becomes hyperreactive to vasoconstrictor mediators, and reduced availability of nitric oxide from the endothelium removes a normal protective brake on vascular tone. Spasm can occur in coronary arteries that appear angiographically normal or at sites of only mild, non-obstructive plaque.

Recognized triggers include cold exposure, cocaine use, and emotional stress, all of which increase sympathetic tone and can provoke spasm in a susceptible artery.

Episodes occur predominantly at rest, classically in the early morning hours when sympathetic tone is naturally higher. The electrocardiogram during an episode characteristically shows transient ST-segment elevation rather than the ST depression typical of demand-driven ischemia, because the spasm produces transmural rather than subendocardial ischemia. Symptoms relieve rapidly with sublingual nitroglycerin.

Calcium channel blockers are the first-line treatment because they directly counteract the calcium-mediated smooth muscle hyperreactivity that causes the spasm. Long-acting nitrates are used as an adjunct.

Patients have typical anginal symptoms and a positive stress test, but coronary angiography shows no significant obstruction in the major epicardial arteries. Specialized functional testing can confirm reduced coronary flow reserve when the diagnosis is uncertain. Microvascular angina is more common in postmenopausal women and in patients with hypertension or diabetes.

Sublingual nitroglycerin, which works primarily on larger vessels and on the venous system, may be less effective in microvascular angina than in stable exertional angina. Management typically requires a combination of agents, including beta-blockers and calcium channel blockers, with response that varies between patients.