Calcium antagonists in coronary artery disease and hypertension. Time for reevaluation?

Abstract

Calcium antagonists have been used in patients with cardiovascular diseases for about 2 decades. Regulatory authorities have approved the use of calcium antagonists in individuals with angina pectoris to relieve chest pain or with hypertension to lower blood pressure. As a class, they are among the most widely used drugs for treatment of cardiovascular conditions. Numerous randomized placebo-controlled studies have demonstrated the value of these agents for relieving symptoms in patients with angina, an action generally associated with increased exercise tolerance in formal exercise testing. However, no study in which a calcium antagonist was used in stable angina pectoris or other clinical manifestations of coronary artery disease has yet to demonstrate convincingly a reduction in morbidity (eg, reinfarction or stroke) or mortality. In part, this gap in our information may be because few large, long-term clinical trials have been designed to test these questions and perhaps because relief of angina per se is a worthwhile goal of therapy in symptomatic patients. However, data accumulated from clinical trials conducted over the last decade have raised concerns as to whether some or all of the calcium antagonists increase morbidity (eg, worsen unstable angina,1 increase heart failure,2 or increase the risk of infarction3 ) and mortality.4 These data on the potential adverse effects of calcium antagonists have been obtained from patients who have a variety of clinical manifestations of coronary artery disease, including stable angina pectoris,5 unstable angina,1 6 and acute myocardial infarction (MI),7 during long-term use after MI,7 and heart failure.8 Patients who have these various conditions often have several similarities in clinical course and some common underlying pathophysiological abnormalities. Therefore, these data, obtained from a broad group of patients with coronary artery disease, have widespread clinical applicability. Further direct evidence of a …