Nifepidine therapy for patients with threatened and acute myocardial infarction: A randomized, double-blind, placebo-controlled comparison

Abstract

Preliminary clinical and laboratory observations suggest that nifedipine might prevent progression of threatened myocardial infarction by reversing coronary spasm or might limit necrosis during the course of acute myocardial infarction. We screened 3143 patients with ischemic pain of >45 min duration and randomly assigned 105 eligible patients with threatened myocardial infarction and 66 with acute myocardial infarction to receive nifedipine (20 mg orally every 4 hr for 14 days) or placebo plus standard care. Treatment was started 4.6 ± 0.1 hr after the onset of pain. Infarct size index was calculated by the MB-creatine kinase (CK) method and expressed as CK-geq/m2 ± SE. The incidence of progression to infarction among patients with threatened myocardial infarction was not significantly altered by nifedipine (36 of 48 [75%] for placebo-treated and 43 of 57 [75%] for nifedipine-treated patients). Furthermore, infarct size index was similar among placebo- and nifedipine-treated patients (16.9 ± 1.5 MB-CK-geq/m2, n = 65, and 17.0 ± 1.5 MB-CK-geq/m2, n = 68, respectively) with threatened myocardial infarction who exhibited infarction and for those with acute myocardial infarction. Among the 171 eligible patients randomly assigned to drug or placebo, 6 month mortality did not differ significantly (8.5% for placebo vs 10.1% for nifedipine, NS), but mortality in the 2 weeks after randomization was significantly higher for nifedipine-treated patients (0% for placebo compared with 7.9% for nifedipine, p = .018). There were no significant differences in 2 week and 6 month mortalities in the group of all participating patients, which included 10 patients randomly assigned therapy but retrospectively determined to be ineligible. Two week mortality for this group (n = 181) was 2.3% for placebo- and 7.5% for nifedipine-treated patients and 6 month mortality was 11.4% for placebo- and 10.8% for nifedipine-treated patients. Thus, nifedipine therapy did not prevent progression of threatened myocardial infarction to the acute event or limit infarct size in patients who experienced infarction. There was a statistically significant increase in 2 week mortality with nifedipine in the group of eligible patients randomly assigned to a regimen, but mortality was balanced when results were analyzed for all patients taking part in the randomization protocol.