(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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M. Gheorghiade, W. S. Colucci, and K. Swedberg {beta}-Blockers in Chronic Heart Failure Circulation, April 1, 2003; 107(12): 1570 - 1575. [Full Text] [PDF]
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T. Simon, M. Mary-Krause, C. Funck-Brentano, Ph. Lechat, P. Jaillon, and on behalf of CIBIS II investigators Bisoprolol dose-response relationship in patients with congestive heart failure: a subgroup analysis in the cardiac insufficiency bisoprolol study (CIBIS II) Eur. Heart J., March 2, 2003; 24(6): 552 - 559. [Abstract] [Full Text] [PDF]
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A P Maggioni, G Sinagra, C Opasich, E Geraci, M Gorini, E Gronda, D Lucci, G Tognoni, E Balli, and L Tavazzi Treatment of chronic heart failure with {beta} adrenergic blockade beyond controlled clinical trials: the BRING-UP experience Heart, March 1, 2003; 89(3): 299 - 305. [Abstract] [Full Text] [PDF]
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H. Krum, E. B. Roecker, P. Mohacsi, J. L. Rouleau, M. Tendera, A. J. S. Coats, H. A. Katus, M. B. Fowler, M. Packer, and for the Carvedilol Prospective Randomized Cumulati Effects of Initiating Carvedilol in Patients With Severe Chronic Heart Failure: Results From the COPERNICUS Study JAMA, February 12, 2003; 289(6): 712 - 718. [Abstract] [Full Text] [PDF]
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P. Agostoni, M. Guazzi, M. Bussotti, S. De Vita, and P. Palermo Carvedilol Reduces the Inappropriate Increase of Ventilation During Exercise in Heart Failure Patients Chest, December 1, 2002; 122(6): 2062 - 2067. [Abstract] [Full Text] [PDF]
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A. Staudt, M. Bohm, F. Knebel, Y. Grosse, C. Bischoff, A. Hummel, J. B. Dahm, A. Borges, N. Jochmann, K. D. Wernecke, et al. Potential Role of Autoantibodies Belonging to the Immunoglobulin G-3 Subclass in Cardiac Dysfunction Among Patients With Dilated Cardiomyopathy Circulation, November 5, 2002; 106(19): 2448 - 2453. [Abstract] [Full Text] [PDF]
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M. L. Kukin {beta}-Blockers in Chronic Heart Failure: Considerations for Selecting an Agent Mayo Clin. Proc., November 1, 2002; 77(11): 1199 - 1206. [Abstract] [PDF]
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 J. R. R. Heyen, E. R. Blasi, K. Nikula, R. Rocha, H. A. Daust, G. Frierdich, J. F. Van Vleet, P. De Ciechi, E. G. McMahon, and A. E. Rudolph Structural, functional, and molecular characterization of the SHHF model of heart failure Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1775 - H1784. [Abstract] [Full Text] [PDF]
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N. Spyrou, S. D. Rosen, F. Fath-Ordoubadi, R. Jagathesan, R. Foale, J. S. Kooner, and P. G. Camici Myocardial beta-adrenoceptor densityone month after acute myocardial infarctionpredicts left ventricular volumes at six months J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1216 - 1224. [Abstract] [Full Text] [PDF]
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J. Wikstrand, A. k. Hjalmarson, F. Waagstein, B. j. Fagerberg, S. Goldstein, J. Kjekshus, H. Wedel, and MERIT-HF Study Group Dose of metoprolol CR/XL and clinical outcomes in patients with heart failure: Analysis of the experience in metoprolol CR/XL randomized intervention trial in chronic heart failure (MERIT-HF) J. Am. Coll. Cardiol., August 7, 2002; 40(3): 491 - 498. [Abstract] [Full Text] [PDF]
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R. V. Bobadilla Current research on carvedilol in heart failure Crit. Care Nurse, August 1, 2002; 22(4): 14 - 16. [Full Text] [PDF]
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A. M. Pritchett and M. M. Redfield {beta}-Blockers: New Standard Therapy for Heart Failure Mayo Clin. Proc., August 1, 2002; 77(8): 839 - 846. [Abstract] [PDF]
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J. M. Hare Cardiac-Resynchronization Therapy for Heart Failure N. Engl. J. Med., June 13, 2002; 346(24): 1902 - 1905. [Full Text] [PDF]
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C. Zugck, A. Haunstetter, C. Kruger, R. Kell, D. Schellberg, W. Kubler, and M. Haass Impact of beta-blocker treatment on the prognostic value of currently used risk predictors in congestive heart failure J. Am. Coll. Cardiol., May 15, 2002; 39(10): 1615 - 1622. [Abstract] [Full Text] [PDF]
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B. D. Lowes, E. M. Gilbert, W. T. Abraham, W. A. Minobe, P. Larrabee, D. Ferguson, E. E. Wolfel, J. Lindenfeld, T. Tsvetkova, A. D. Robertson, et al. Myocardial Gene Expression in Dilated Cardiomyopathy Treated with Beta-Blocking Agents N. Engl. J. Med., May 2, 2002; 346(18): 1357 - 1365. [Abstract] [Full Text] [PDF]
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M. Taccetta-Chapnick Using Carvedilol to Treat Heart Failure Crit. Care Nurse, April 1, 2002; 22(2): 36 - 58. [Full Text] [PDF]
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P. Merlet, L. Hittinger, J. L. Dubois-Rande, and A. Castaigne Myocardial Adrenergic Dysinnervation in Dilated Cardiomyopathy: Cornerstone or Epiphenomenon? J. Nucl. Med., April 1, 2002; 43(4): 536 - 539. [Full Text] [PDF]
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B. Riegel, B. Carlson, Z. Kopp, B. LePetri, D. Glaser, and A. Unger Effect of a Standardized Nurse Case-Management Telephone Intervention on Resource Use in Patients With Chronic Heart Failure Arch Intern Med, March 25, 2002; 162(6): 705 - 712. [Abstract] [Full Text] [PDF]
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J. M. Foody, M. H. Farrell, and H. M. Krumholz {beta}-Blocker Therapy in Heart Failure: Scientific Review JAMA, February 20, 2002; 287(7): 883 - 889. [Abstract] [Full Text] [PDF]
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M. H. Farrell, J. M. Foody, and H. M. Krumholz {beta}-Blockers in Heart Failure: Clinical Applications JAMA, February 20, 2002; 287(7): 890 - 897. [Abstract] [Full Text] [PDF]
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A. Nohria, E. Lewis, and L. W. Stevenson Medical Management of Advanced Heart Failure JAMA, February 6, 2002; 287(5): 628 - 640. [Abstract] [Full Text] [PDF]
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B. M. Massie Neurohormonal blockade in chronic heart failure: How much is enough? can there be too much? J. Am. Coll. Cardiol., January 2, 2002; 39(1): 79 - 82. [Full Text] [PDF]
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 S.M. DALLABRIDA and M.A. RUPNICK Vascular Endothelium in Tissue Remodeling: Implications for Heart Failure Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 417 - 428. [Abstract] [PDF]
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S. Reiken, M. Gaburjakova, J. Gaburjakova, K.-l. He, A. Prieto, E. Becker, G.-h. Yi, J. Wang, D. Burkhoff, and A. R. Marks {beta}-Adrenergic Receptor Blockers Restore Cardiac Calcium Release Channel (Ryanodine Receptor) Structure and Function in Heart Failure Circulation, December 4, 2001; 104(23): 2843 - 2848. [Abstract] [Full Text] [PDF]
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J. Lindenfeld, A. D. Robertson, B. D. Lowes, M. R. Bristow, and for the MOCHA Investigators Aspirin impairs reverse myocardial remodeling in patients with heart failure treated with beta-blockers J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1950 - 1956. [Abstract] [Full Text] [PDF]
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C. Stellbrink, O.-A. Breithardt, A. Franke, S. Sack, P. Bakker, A. Auricchio, T. Pochet, R. Salo, A. Kramer, and J. Spinelli Impact of cardiac resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1957 - 1965. [Abstract] [Full Text] [PDF]
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T. Kubo, E. R. Azevedo, G. E. Newton, J. D. Parker, and J. S. Floras Lack of evidence for peripheral alpha1- adrenoceptor blockade during long-term treatment of heart failure with carvedilol J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1463 - 1469. [Abstract] [Full Text] [PDF]
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