Differential effects of beta-blockers in patients with heart failure - A prospective, randomized, double-blind comparison of the long-term effects ofmetoprolol versus carvedilol

Background-Both metoprolol and carvedilol produce hemodynamic and clinical benefits in patients with chronic heart failure; carvedilol exerts greater antiadrenergic effects than metoprolol, but it is unknown whether this phar macological difference results in hemodynamic and clinical differences betw een the 3 drugs. Methods and Results-We randomized 150 patients with heart failure (left ven tricular election fraction less than or equal to 0.35) to double-blind trea tment with either metoprolol or carvedilol. When compared with metoprolol ( 124+/-55 mg/d), patients treated with carvedilol (49+/-18 mg/d) showed larg er increases in left ventricular ejection fraction at rest (+10.9+/-11.0 ve rsus +7.2+/-7.7 U, P=0.038) and in left ventricular stroke volume and strok e work during exercise (both P<0.05) after 13 to 15 months of treatment. In addition, carvedilol produced greater decreases in mean pulmonary artery p ressure and pulmonary wedge pressure, both at rest and during exercise, tha n metoprolol (all P<0.05), In contrast, the metoprolol group showed greater increases in maximal exercise capacity than the carvedilol group (P=0.035) , but the 3 drugs improved symptoms, submaximal exercise tolerance, and qua lity of life to a similar degree. After a mean of 23+/-11 months of follow- up, 21 patients in the metoprolol group and 17 patients in the carvedilol g roup died or underwent urgent transplantation. Conclusions-The present study demonstrates that during long-term therapy, c arvedilol improves cardiac performance to a greater extent than metoprolol when administered to patients with heart failure in the doses shown to be e ffective in clinical trials. These differences were likely related to a gre ater antiadrenergic activity of carvedilol.