Abstract
A multicenter, double-blind, randomized study was performed to evaluate the cardioprotective effects of diltiazem administered to patients with MB creatine kinase-confirmed acute non-Q-wave myocardial infarction. Nine centers enrolled a total of 576 patients, with 287 receiving diltiazem and 289 receiving placebo (90 mg every 6 h). Treatment was started 24-72 h after onset of clinical infarction and continued for up to 14 days. The primary endpoint was recurrent myocardial infarction, which was defined as an abnormal reelevation in plasma MB creatine kinase during the 14-day study period. MB creatine kinase samples were obtained every 12 h after randomization and were assayed by a central core laboratory using the glass bead adsorption method. Recurrent myocardial infarction was documented in 27 patients in the placebo group (9.3%) versus 15 patients in the diltiazem group (5.2%) - reflecting a reduction of 51.2% in the cumulative life-table reinfarction rate (p = 0.0297). The significance of this difference for treatment effect remained at a comparable α-level after individual adjustments (Cox model) for age, gender, previous infarction, obesity, site of qualifying infarction, Killip Class at entry, and concurrent use of β-blocking agents. Diltiazem also reduced the incidence of refractory postinfarction angina necessitating study withdrawal, and angina associated with transient ST-T changes by 49.7% (p = 0.0345) and by 28% (p = 0.0057), respectively. Atrioventricular block, bradycardia, hypotension, and sinus pauses were more common in patients receiving diltiazem, but the drug was well tolerated overall despite the fact that 61% of diltiazem patients were also taking β-blockers. These results indicate that high-dose diltiazem is well tolerated, safe, and effective in the prevention of early reinfarction and severe angina after non-Q-wave infarction.