Reappraisal of the importance of heart rate as a risk factor for cardiovascular morbidity and mortality.

Heart rate is a key determinant of myocardial oxygen consumption. Several lines of evidence support a consistent association between heart rate and cardiovascular mortality. Increments in heart rate are positively related to cardiovascular and sudden death in patients with hypertension or previous myocardial infarction and in the elderly with heart disease. This relationship is important because a number of commonly used cardiovascular agents, such as beta-blockers and calcium antagonists (CAs), can affect heart rate. Beta-blockers decrease heart rate and reduce morbidity and mortality in post-myocardial infarction patients. The CAs are a structurally diverse group of agents with different physiologic effects. The dihydropyridine CAs are not associated with a reduction in heart rate. In fact, often they can cause reflex tachycardia as a result of potent systemic vasodilator action, which may provoke angina, especially in patients with ischemic heart disease. The nondihydropyridine CAs verapamil and diltiazem reduce heart rate but are associated with negative inotropy. Mibefradil, the first member of a new class of CAs, reduces heart rate and is not associated with negative inotropic effects. This unique pharmacologic profile may be of great value in treating hypertensive patients, particularly those with coexisting ischemic heart disease, and also patients with angina pectoris alone. However, the clinical benefit of pharmacologically reducing heart rate with mibefradil needs to be demonstrated in controlled trials.