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(Circulation. 1996;94:2800-2806.)
© 1996 American Heart Association, Inc.
Articles |
Carvedilol Inhibits Clinical Progression in Patients With Mild Symptoms of Heart Failure
the Boston University School of Medicine, Boston, Mass (W.S.C.); the College of Physicians and Surgeons, Columbia University, New York, NY (M.P., J.D.S.-B.); University of Colorado Health Sciences Center, Denver (M.R.B.); University of Utah School of Medicine, Salt Lake City (E.M.G.); University of Minnesota Medical School, Minneapolis (J.N.C.); Stanford University School of Medicine, Palo Alto, Calif (M.B.F.); Nebraska Heart Institute, Lincoln (S.K.K.); University of Oregon School of Medicine, Portland (R.H.); Presbyterian University Hospital, Pittsburgh (B.F.U.); Heart Institute of Nevada, Las Vegas (J.A.B.); and SmithKline Beecham Pharmaceuticals, King of Prussia, Pa (S.T.Y., T.L.H., M.A.L.).
Background We tested the hypothesis that carvedilol inhibits clinical progression in patients with mildly symptomatic heart failure due to left ventricular (LV) systolic dysfunction.
Methods and Results Patients (n=366) who had mildly symptomatic heart failure with an LV ejection fraction (LVEF) 
0.35, had minimal functional impairment (defined as the ability to walk 450 to 550 m on a 6-minute walk test), and were receiving optimal standard therapy, including ACE inhibitors, were randomized double-blind to carvedilol (n=232) or placebo (n=134) and followed up for 12 months. The primary end point was clinical progression, defined as death due to heart failure, hospitalization for heart failure, or a sustained increase in heart failure medications. Clinical progression of heart failure occurred in 21% of placebo patients and 11% of carvedilol patients, reflecting a 48% (P=.008) reduction in the primary end point of heart failure progression (relative risk, 0.52; CI, 0.32 to 0.85). This effect of carvedilol was not influenced by sex, age, race, cause of heart failure, or baseline LVEF. Carvedilol also significantly improved several secondary end points, including LVEF, heart failure score, NYHA functional class, and the physician and patient global assessments. Carvedilol reduced all-cause mortality but had no effects on the Minnesota Living With Heart Failure scale, the distance walked in 9 minutes on a self-powered treadmill, or cardiothoracic index. The drug was well tolerated.
Conclusions Carvedilol, when added to standard therapy, including an ACE inhibitor, reduces clinical progression in patients who are only mildly symptomatic with well-compensated heart failure.
Key Words: carvedilol • heart failure • receptors, adrenergic, beta • antioxidants
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J. N. Cohn, R. Ferrari, N. Sharpe, and on Behalf of an International Forum on Cardiac Rem Cardiac remodeling--concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling J. Am. Coll. Cardiol., March 1, 2000; 35(3): 569 - 582. [Abstract] [Full Text] [PDF]
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H. Schunkert The importance of early intervention in CHF -- signs and symptom relief Journal of Renin-Angiotensin-Aldosterone System, March 1, 2000; 1(1_suppl): 17 - 23. [Abstract] [PDF]
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M. R. Bristow {beta}-Adrenergic Receptor Blockade in Chronic Heart Failure Circulation, February 8, 2000; 101(5): 558 - 569. [Full Text] [PDF]
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Effects of Metoprolol CR in Patients With Ischemic and Dilated Cardiomyopathy : The Randomized Evaluation of Strategies for Left Ventricular Dysfunction Pilot Study Circulation, February 1, 2000; 101(4): 378 - 384. [Abstract] [Full Text] [PDF]
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J. E. Sanderson, S. K. W. Chan, G. Yip, L. Y. C. Yeung, K. W. Chan, K. Raymond, and K. S. Woo Beta-blockade in heart failure: A comparison of carvedilol with metoprolol J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1522 - 1528. [Abstract] [Full Text] [PDF]
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P S Macdonald, A M Keogh, C Aboyoun, M Lund, R Amor, and D McCaffrey Impact of concurrent amiodarone treatment on the tolerability and efficacy of carvedilol in patients with chronic heart failure Heart, November 1, 1999; 82(5): 589 - 593. [Abstract] [Full Text]
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K. A. Crispell, A. Wray, H. Ni, D. J. Nauman, and R. E. Hershberger Clinical profiles of four large pedigrees with familial dilated cardiomyopathy: Preliminary recommendations for clinical practice J. Am. Coll. Cardiol., September 1, 1999; 34(3): 837 - 847. [Abstract] [Full Text] [PDF]
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M. L. Kukin, J. Kalman, R. H. Charney, D. K. Levy, C. Buchholz-Varley, O. N. Ocampo, and C. Eng Prospective, Randomized Comparison of Effect of Long-Term Treatment With Metoprolol or Carvedilol on Symptoms, Exercise, Ejection Fraction, and Oxidative Stress in Heart Failure Circulation, May 25, 1999; 99(20): 2645 - 2651. [Abstract] [Full Text] [PDF]
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P. S. Macdonald, A. M. Keogh, C. L. Aboyoun, M. Lund, R. Amor, and D. J. McCaffrey Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure J. Am. Coll. Cardiol., March 15, 1999; 33(4): 924 - 931. [Abstract] [Full Text] [PDF]
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D. L. Dries, D. V. Exner, B. J. Gersh, H. A. Cooper, P. E. Carson, and M. J. Domanski Racial Differences in the Outcome of Left Ventricular Dysfunction N. Engl. J. Med., February 25, 1999; 340(8): 609 - 616. [Abstract] [Full Text] [PDF]
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W. Carlson and K. Oberg Clinical Pharmacology of Carvedilol Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(4): 205 - 218. [Abstract] [PDF]
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W. H. Frishman Carvedilol N. Engl. J. Med., December 10, 1998; 339(24): 1759 - 1765. [Full Text] [PDF]
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C. Communal, K. Singh, D. R. Pimentel, and W. S. Colucci Norepinephrine Stimulates Apoptosis in Adult Rat Ventricular Myocytes by Activation of the ß-Adrenergic Pathway Circulation, September 29, 1998; 98(13): 1329 - 1334. [Abstract] [Full Text] [PDF]
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P. Lechat, M. Packer, S. Chalon, M. Cucherat, T. Arab, and J.-P. Boissel Clinical Effects of ß-Adrenergic Blockade in Chronic Heart Failure : A Meta-Analysis of Double-Blind, Placebo-Controlled, Randomized Trials Circulation, September 22, 1998; 98(12): 1184 - 1191. [Abstract] [Full Text] [PDF]
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R. J. Myerburg, R. Mitrani, A. Interian Jr, and A. Castellanos Interpretation of Outcomes of Antiarrhythmic Clinical Trials : Design Features and Population Impact Circulation, April 21, 1998; 97(15): 1514 - 1521. [Full Text] [PDF]
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K. Chatterjee Heart Failure Therapy in Evolution Circulation, December 1, 1996; 94(11): 2689 - 2693. [Full Text]
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