Acute intervention with captopril during thrombolysis in patients with first anterior myocardial infarction

Abstract

The study was designed to examine the safety and efficacy of acute interventional use of captopril on left ventricular volumes, ventricular arrhythmias and neurohormones during thrombolysis in patients with a first anterior myocardial infarction, within 6 h of onset of symptoms. Left ventricular dysfunction and prognosis after myocardial infarction can be improved by angiotensin converting enzyme inhibition started after the ischaemic phase. Experimental evidence suggests that intervention during thrombolysis may lead to even further benefit. In a randomized, double-blind placebo-controlled trial, 298 patients with a first anterior myocardial infarction, eligible for thrombolytic therapy were treated with captopril 6.25 mg or placebo, started immediately upon streptokinase infusion and titrated to 2.5 mg t.i.d.. The efficacy of captopril by an intention-to-treat-analysis to reduce left ventricular volumes, ventricular arrhythmias, neurohumoral activation and enzymatic infarct size was measured. During dose titration, mean blood pressure and heart rate were similar in both groups. However, hypotension after the first dose was reported in 18 patients on placebo and 31 patients on captopril (P<0.05). At discharge, 80% of patients were on study medication. Left ventricular volumes were significantly increased in both groups at 3 months, but they tended to be lower in the captopril group; however, the differences were not statistically significant. The incidence of accelerated idioventricular rhythm and non-sustained ventricular tachycardia in captopril patients was lower than in placebo patients (P<0.05), parallelled by transiently lower norepinephrine levels (P<0.05) upon thrombolysis. In addition, enzymatic infarct size was smaller in captopril patients, especially in larger infarcts (P<0.05), and a 34% (95% confidence interval; 0–56%) lower incidence of heart failure during 3 months follow-up was reported in the captopril group. Captopril is well tolerated, although hypotension after the first dose was more common than in patients on placebo. In agreement with experimental studies, captopril reduces repetitive ventricular arrhythmias and catecholamine levels in the acute thrombolytic phase of myocardial infarction. Although left ventricular volumes were not significantly smaller in captopril patients, in the chronic phase, these patients showed a reduced incidence of heart failure. This study was carried out under auspices of the Interuniversity Institute of the Netherlands (ICIN) and the Working Group of Cardiovascular Research the Netherlands (WCN). Financial support was received from Bristol-Myers Squibb, Pharmaceutical Research Institute, Princeton, N.J., U.S.A.