Differential Effects of b-Blockers in Patients With Heart Failure A Prospective, Randomized, Double-Blind Comparison of the Long-Term Effects of Metoprolol 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 pharmacological difference results in hemodynamic and clinical differences between the 2 drugs. Methods and Results—We randomized 150 patients with heart failure (left ventricular ejection fraction #0.35) to double-blind treatment with either metoprolol or carvedilol. When compared with metoprolol (124655 mg/d), patients treated with carvedilol (49618 mg/d) showed larger increases in left ventricular ejection fraction at rest (110.9611.0 versus 17.267.7 U, P50.038) and in left ventricular stroke volume and stroke work during exercise (both P,0.05) after 13 to 15 months of treatment. In addition, carvedilol produced greater decreases in mean pulmonary artery pressure and pulmonary wedge pressure, both at rest and during exercise, than metoprolol (all P,0.05). In contrast, the metoprolol group showed greater increases in maximal exercise capacity than the carvedilol group (P50.035), but the 2 drugs improved symptoms, submaximal exercise tolerance, and quality of life to a similar degree. After a mean of 23611 months of follow-up, 21 patients in the metoprolol group and 17 patients in the carvedilol group died or underwent urgent transplantation. Conclusions—The present study demonstrates that during long-term therapy, carvedilol improves cardiac performance to a greater extent than metoprolol when administered to patients with heart failure in the doses shown to be effective in clinical trials. These differences were likely related to a greater antiadrenergic activity of carvedilol. (Circulation. 2000;102:546-551.)