Rationale for the use of calcium antagonists in the treatment of silent myocardial ischemia.

Silent myocardial ischemia, whether it occurs at rest or during exercise, is associated with an unfavorable prognosis and may lead to sudden cardiac death. Agents used to treat silent myocardial ischemia have included nitrates, beta-blockers, and calcium antagonists (CAs). Despite treatment with traditional anti-ischemic agents, studies have shown that up to 40% of patients who receive what is considered to be clinically optimal antianginal therapy continue to have daily episodes of silent myocardial ischemia. The use of nitrates and beta-blockers is sometimes confounded by issues of tolerance and tolerability. Although the CAs have been found to be effective in decreasing the duration and frequency of episodes of silent ischemia, in general beta-blockers produce a greater reduction in these variables. Thus a need for effective and tolerable anti-ischemic agents persists. A new class of CAs, the tetralol derivatives, may show promise in this regard. The first of this new class, mibefradil, is characterized by selective blockade of T-type calcium-ion channels and has been shown in a few studies to reduce the frequency and duration of asymptomatic ischemic episodes in patients with stable exertional angina pectoris. Large-scale clinical trials are necessary before the efficacy and tolerability of this new CA can be compared fully with those of the beta-blockers and currently available CAs.