Beneficial effects of intravenous and oral carvedilol treatment in acute myocardial infarction. A placebo-controlled, randomized trial.

Abstract

Evidence of efficacy and safety of beta-blockers after thrombolysis for acute myocardial infarction (AMI) is equivocal. Newer beta-blockers such as carvedilol have not been tested in this setting. This study investigated the effects of acute (intravenous) and long-term (6 months, oral) treatment with carvedilol versus placebo in 151 consecutive patients with AMI. Exercise ECG, ambulatory monitoring, and two-dimensional echocardiography were performed before hospital discharge and at 3 and 6 months. All patients were followed up and cardiovascular events recorded. The Cox proportional hazards model was used to compare time from randomization with the occurrence of a cardiovascular event, and Kaplan-Meier survival curves were calculated. Carvedilol was found to be safe, and it significantly reduced cardiac events compared with placebo (18 on carvedilol and 31 on placebo, P < .02). Fifty-four patients had heart failure at study entry; 34 received carvedilol. There were no adverse effects of carvedilol therapy and no excess events in this subgroup. Carvedilol produced significant reductions in heart rate (P < .0001), blood pressure (P < .005) at rest, and rate-pressure product at peak exercise (P < .003), but exercise capacity was unchanged. Left ventricular ejection fraction was not altered significantly by carvedilol, but stroke volume was higher at pre-hospital discharge examination (63 versus 53 mL; P < .01). Diastolic filling of the left ventricle (E/A ratio) was also improved (1.2 versus 0.9; P < .001). In a subgroup with left ventricular ejection fraction < 45% (n = 49 patients; 24 on carvedilol and 25 on placebo), carvedilol showed attenuation of remodeling. Carvedilol was well tolerated and safe to use in patients immediately after AMI, including those with heart failure, and significantly improved outcome.