(Circulation. 1996;94:2807-2816.)
© 1996 American Heart Association, Inc.
Articles |
Carvedilol Produces Dose-Related Improvements in Left Ventricular Function and Survival in Subjects With Chronic Heart Failure
the University of Colorado Health Sciences Center, Denver (M.R.B., W.T.A.), University of Utah Health Sciences Center (E.M.G.), University of North Carolina at Chapel Hill (K.F.A.), Stanford University Hospital, Palo Alto, Calif (M.B.F.), Oregon Health Sciences Center, Portland (R.E.H.), University of Minnesota, Minneapolis (S.H.K.), University of California at Los Angeles Medical Center (K.A.N.), Sharp-Reese Stealy Medical Clinic, San Diego, Calif (H.I.), Nebraska Heart Institute, Lincoln (S.K.), and SmithKline Beecham Pharmaceuticals, King of Prussia, Pa (S.Y., N.S.).
Background We conducted a multicenter, placebo-controlled trial designed to establish the efficacy and safety of carvedilol, a "third-generation" ß-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.
Key Words: carvedilol • heart failure • exercise • vasodilation • receptors, adrenergic, beta
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