BENEFICIAL-EFFECTS OF INTRAVENOUS AND ORAL CARVEDILOL TREATMENT IN ACUTE MYOCARDIAL-INFARCTION - A PLACEBO-CONTROLLED, RANDOMIZED TRIAL

Background Evidence of efficacy and safety of beta-blockers after thro mbolysis for acute myocardial infarction (AMI) is equivocal. Newer bet a-blockers such as carvedilol have not been tested in this setting. Me thods and Results This study investigated the effects of acute (intrav enous) and long-term (6 months, oral) treatment with carvedilol versus placebo in 151 consecutive patients with AMI. Exercise ECG, ambulator y monitoring, and two-dimensional echocardiography were performed befo re hospital discharge and at 3 and 6 months. All patients were followe d 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 calcu lated. Carvedilol was found to be safe, and it significantly reduced c ardiac events compared with placebo (18 on carvedilol and 31 on placeb o, P<.02). Fifty-four patients had heart failure at study entry; 34 re ceived carvedilol. There were no adverse effects of carvedilol therapy and no excess events in this subgroup. Carvedilol produced significan t reductions in heart rate (P<.0001), blood pressure (P<.005) at rest, and rate-pressure product al peak exercise (P<.003), but exercise cap acity was unchanged. Left ventricular ejection fraction was not altere d significantly by carvedilol, but stroke volume was higher al pre-hos pital discharge examination (63 versus 53 mL; P<.01). Diastolic fillin g 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. Conclusions Carvedilol was well tolerated and safe to use in patients immediately after AMI, including those wit h heart failure, and significantly improved outcome.