The role of calcium antagonists in the treatment of myocardial ischemia

Abstract

Calcium antagonists are often prescribed for treatment of ischemic heart disease. Therapeutic activity is achieved by reducing myocardial oxygen requirements and by increasing blood supply in ischemic heart disease associated with coronary artery spasms. The efficacy of calcium antagonists depends on the type and clinical presentation of ischemic heart disease: (1) in vasospastic angina (variant angina, short episodes of angina at rest), first-line therapy with calcium antagonists will reduce the number of ischemic episodes and improve long-term prognosis. (2) In effort angina the efficacy of calcium antagonists is comparable with that of β blockers. (3) In unstable angina the use of calcium antagonists is controversial. Large-scale studies with nifedipine showed no benefit when it was given alone but an additive effect in patients pretreated with β blockers. In contrast, diltiazem and verapamil appear to have comparable efficacy to β blockers in patients with unstable angina. (4) After myocardial infarction the results of treatment with calcium antagonists have been disappointing. Nifedipine and verapamil did not reduce mortality or the incidence of reinfarction. In one study diltiazem significantly reduced the rate of reinfarction in patients who had had a non-Q wave infarction, but in a recent large-scale multicenter trial it had no effect on mortality and cardiac events in patients with evidence of both Q- and non-Q wave infarctions. Other secondary preventative measures against reinfarction, such as the use of β-blockers and aspirin, appear to be more effective than calcium antagonists. The most frequently prescribed calcium antagonists, verapamil, diltiazem, and nifedipine, each of which represents a different chemical class, have in general similar efficacy in vasospastic and effort angina. Their different pharmacologic profile, such as the slowing of heart rate with verapamil or diltiazem and a more marked vasodilatation with nifedipine and other dihydropyridines, may become clinically relevant in individual patients. The new dihydropyridine derivatives have a pharmacologic profile comparable to that of nifedipine but some of these compounds, especially amiodipine, have more favorable pharmacokinetics, such as a prolonged elimination half-life. These agents may offer the advantage of a more practical dosage regimen for long-term treatment in patients with ischemic heart disease.