Carvedilol had no detectable effect on submaximal exercise, but reduced all-cause mortality risk by 73% (P<0.001) and improved left ventricular function compared with placebo.
RCT (n=345)
Placebo-controlled
Randomized
Yes
Does carvedilol improve submaximal exercise capacity, left ventricular function, and survival in subjects with mild to moderate, stable chronic heart failure?
Although carvedilol did not improve submaximal exercise capacity, it significantly improved left ventricular ejection fraction, survival, and hospitalization rates in patients with mild to moderate chronic heart failure.
BACKGROUND: We conducted a multicenter, placebo-controlled trial designed to establish the efficacy and safety of carvedilol, a "third-generation" beta -blocking agent with vasodilator properties, in chronic heart failure. METHODS AND RESULTS: Three hundred forty-five subjects with mild to moderate, stable chronic heart failure were randomized to receive 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 efficacy parameter was submaximal exercise measured by two different techniques, the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exercise as measured by either technique. However, carvedilol was associated with dose-related improvements in LV function (by 5, 6, and 8 ejection fraction EF units in the low-, medium-, and high-dose carvedilol groups, respectively, compared with 2 EF units with placebo, P < .001 for linear dose response) and survival (respective crude mortality rates 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 groups were combined, the all-cause actuarial mortality risk was lowered by 73% in carvedilol-treated subjects (P < .001). Carvedilol also lowered the hospitalization rate (by 58% to 64%, P = .01) and was generally well tolerated. CONCLUSIONS: In subjects with mild to moderate heart failure from systolic dysfunction, carvedilol produced dose-related improvements in LV function and dose-related reductions in mortality and hospitalization rate.
Bristow et al. (1996) conducted an RCT in Chronic heart failure (n=345). Carvedilol vs. Placebo was evaluated on Submaximal exercise measured by the 6-minute corridor walk test and the 9-minute self-powered treadmill test. Carvedilol had no detectable effect on submaximal exercise, but reduced all-cause mortality risk by 73% (P<0.001) and improved left ventricular function compared with placebo.