Calcium antagonists for Prinzmetal's variant angina, unstable angina and silent myocardial ischemia: therapeutic tool and probe for identification of pathophysiologic mechanisms

Abstract

The calcium antagonists provide a unique tool to reduce myocardial oxygen demand and prevent increases in coronary vasomotor tone. For patients with Prinzmetal's variant angina, diltiazem, nifedipine and verapamil are extremely effective in preventing episodes of coronary vasospasm and symptoms of ischemia. Unstable angina pectoris is a more complex pathophysiologic syndrome with episodes of ischemia due to increases in coronary vasomotor tone, intermittent platelet aggregation or alterations in the underlying atherosclerotic plaque. Each of the calcium antagonists is effective as monotherapy in decreasing the frequency of angina at rest. Nifedipine is the only calcium antagonist that has been studied in a combination regimen with beta blockers and nitrates for patients with unstable angina, and control of angina is better with the combination regimen than with either form of therapy alone. Although symptoms of myocardial ischemia in unstable angina are reduced by calcium antagonists, these agents do not seem to decrease the incidence of adverse outcomes. Antiplatelet therapy appears to improve morbidity and mortality in patients with unstable angina, suggesting that thrombus formation may play a central role in that disorder. Episodes of silent or asymptomatic myocardial ischemia, identified by ST-segment monitoring, occur in a variety of disorders of coronary disease. Among patients with Prinzmetal's variant angina and unstable angina, episodes of silent ischemia appear to be as frequent as episodes of angina and the calcium antagonists are effective in decreasing episodes of ischemia regardless of the presence or absence of symptoms. Persisting episodes of silent ischemia among patients with unstable angina despite maximal medical therapy identify patients at high risk for an early unfavorable outcome. Among patients with stable exertional angina, episodes of silent ischemia may be up to 5 times as frequent as episodes of angina, and may be due to increases in coronary vasomotor tone, transient platelet aggregation or increases in myocardial oxygen demand. Preliminary experience suggests that calcium antagonists and beta blockers are effective in decreasing episodes of silent ischemia in patients with stable exertional angina and that a combination regimen may be more effective than either form of therapy alone.