CARVEDILOL PRODUCES DOSE-RELATED IMPROVEMENTS IN LEFT-VENTRICULAR FUNCTION AND SURVIVAL IN SUBJECTS WITH CHRONIC HEART-FAILURE

Background We conducted a multicenter, placebo-controlled trial design ed to establish the efficacy and safety of carvedilol, a ''third-gener ation'' beta-blocking agent with vasodilator properties, in chronic he art failure. Methods and Results Three hundred forty-five subjects wit h mild to moderate, stable chronic heart failure: were randomized to r eceive treatment with placebo, 6.25 mg BID carvedilol (low-dose group) , 12.5 mg BID carvedilol (medium-dose group), or 25 mg BID carvedilol (high-dose group). After a 2- to 4-week up-titration period, subjects remained on study medication for a period of 6 months. The primary eff icacy parameter was submaximal exercise measured by two different tech niques, the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exer cise as measured by either technique. However, carvedilol was associat ed with dose-related improvements in LV function (by 5, 6, and 8 eject ion fraction [EF] units in the low-, medium-, and high-dose carvedilol groups, respectively, compared with 2 EF units with placebo, P<.001 f or linear dose response) and survival (respective crude mortality rate s of 6.0%, 6.7%, and 1.1% with increasing doses of carvedilol compared with 15.5% in the placebo group, P<.001). When the three carvedilol g roups were combined, the all-cause actuarial mortality risk was lowere d by 73% in carvedilol-treated subjects (P<.001). Carvedilol also lowe red the hospitalization rate (by 58% to 64%, P=.01) and was generally well tolerated. Conclusions In subjects with mild to moderate heart fa ilure from systolic dysfunction, carvedilol produced dose-related impr ovements in LV function and dose-related reductions in mortality and h ospitalization rate.