(Circulation. 1995;92:212-218.)
© 1995 American Heart Association, Inc.
Articles |
From the AustraliaNew Zealand Heart Failure Research Collaborative Group, Auckland, New Zealand. Members are listed in the "Appendix."
Correspondence to ANZ Heart Failure Trials Office, Clinical Trials Research Unit, Department of Medicine, Auckland Hospital, Private Bag 92024, Auckland, New Zealand. E-mail macmahon@ctru.auckland.ac.nz.
Background ß-Blocker therapy has been shown to increase ejection fraction in patients with heart failure of idiopathic etiology. However, in patients with heart failure of ischemic etiology, the effects of this treatment on left ventricular function remain uncertain, as do the effects on exercise performance and symptoms.
Methods and Results This study investigated the effects of
carvedilol, a ß-blocker with
1-blocking properties, on
left ventricular size and function, maximal and submaximal
exercise performance, and symptoms in 415 patients with stable
heart failure of ischemic etiology (ejection fraction <45%).
After a 2- to 3-week run-in phase on open-label low-dose carvedilol,
patients were randomized to continued treatment with carvedilol (up to
25 mg BID) or to matching placebo. After 6 months, left
ventricular ejection fraction measured by radionuclide
ventriculography had increased by 5.2% (2P<.0001) in the
carvedilol group compared with the placebo group, and left
ventricular end-systolic and end-diastolic
dimensions measured by two-dimensionally guided M-mode
echocardiography had decreased by 2.6 mm
(2P=.0005) and 1.3 mm (2P=.05), respectively.
There were no significant changes in either treadmill exercise duration
or 6-minute walk distance between carvedilol and placebo groups (both
2P>.1); in the carvedilol group, exercise
performance was therefore maintained with a 23% lower
rate-pressure product. Symptoms assessed by the New York Heart
Association (NYHA) scale and the Specific Activity Scale (SAS) were
unchanged in two thirds of patients in both groups, but there was a
small excess of patients whose symptoms worsened and a deficit of
patients whose symptoms improved among those assigned carvedilol (NYHA,
2P=.05; SAS, 2P=.02).
Conclusions In patients with heart failure of ischemic etiology, 6-month treatment with carvedilol improved left ventricular function and maintained exercise performance at a lower rate-pressure product, but symptoms assessed by functional class were slightly worsened. A larger-scale trial is now required to determine whether this treatment will reduce serious morbidity and mortality from heart failure.
Key Words: heart failure ischemic heart disease beta adrenergic blockade
This article has been cited by other articles:
![]() |
W. S. Colucci, T. J. Kolias, K. F. Adams, W. F. Armstrong, J. K. Ghali, S. S. Gottlieb, B. Greenberg, M. I. Klibaner, M. L. Kukin, J. E. Sugg, et al. Metoprolol Reverses Left Ventricular Remodeling in Patients With Asymptomatic Systolic Dysfunction: The REversal of VEntricular Remodeling with Toprol-XL (REVERT) Trial Circulation, July 3, 2007; 116(1): 49 - 56. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Funck-Brentano Beta-blockade in CHF: from contraindication to indication Eur. Heart J. Suppl., June 1, 2006; 8(suppl_C): C19 - C27. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Cohen-Solal, F. Rouzet, A. Berdeaux, D. Le Guludec, E. Abergel, A. Syrota, and P. Merlet Effects of Carvedilol on Myocardial Sympathetic Innervation in Patients with Chronic Heart Failure J. Nucl. Med., November 1, 2005; 46(11): 1796 - 1803. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. G. Esposito, S. G. Thomas, L. Kingdon, and S. Ezzat Anabolic growth hormone action improves submaximal measures of physical performance in patients with HIV-associated wasting Am J Physiol Endocrinol Metab, September 1, 2005; 289(3): E494 - E503. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. G. Olsson, K. Swedberg, A. L. Clark, K. K. Witte, and J. G.F. Cleland Six minute corridor walk test as an outcome measure for the assessment of treatment in randomized, blinded intervention trials of chronic heart failure: a systematic review Eur. Heart J., April 2, 2005; 26(8): 778 - 793. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. F. McBride and C. M. White Critical Differences Among Beta-Adrenoreceptor Antagonists in Myocardial Failure: Debating the MERIT of COMET J. Clin. Pharmacol., January 1, 2005; 45(1): 6 - 24. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. T. Ko, P. R. Hebert, C. S. Coffey, J. P. Curtis, J. M. Foody, A. Sedrakyan, and H. M. Krumholz Adverse Effects of {beta}-Blocker Therapy for Patients With Heart Failure: A Quantitative Overview of Randomized Trials Arch Intern Med, July 12, 2004; 164(13): 1389 - 1394. [Abstract] [Full Text] [PDF] |
||||
![]() |
E Kotlyar, C S Hayward, A M Keogh, M Feneley, and P S Macdonald The impact of baseline left ventricular size and mitral regurgitation on reverse left ventricular remodelling in response to carvedilol: size doesn't matter Heart, July 1, 2004; 90(7): 800 - 801. [Full Text] [PDF] |
||||
![]() |
D B McKenzie and A J Cowley Drug therapy in chronic heart failure Postgrad. Med. J., November 1, 2003; 79(937): 634 - 642. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. J. Cai, D. A. Morgan, W. G. Haynes, J. B. Martins, and H.-C. Lee alpha 2-Adrenergic stimulation is protective against ischemia-reperfusion-induced ventricular arrhythmias in vivo Am J Physiol Heart Circ Physiol, December 1, 2002; 283(6): H2606 - H2611. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
K. C. Wollert and H. Drexler Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Trial: Carvedilol as the Sun and Center of the {beta}-Blocker World? Circulation, October 22, 2002; 106(17): 2164 - 2166. [Full Text] [PDF] |
||||
![]() |
M. Wong, L. Staszewsky, R. Latini, S. Barlera, A. Volpi, Y.-T. Chiang, R. L. Benza, S. O. Gottlieb, T. D. Kleemann, F. Rosconi, et al. Valsartan benefits left ventricular structure and function in heart failure: Val-HeFT echocardiographic study J. Am. Coll. Cardiol., September 4, 2002; 40(5): 970 - 975. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
A. M. Richards, R. Doughty, M. G. Nicholls, S. MacMahon, N. Sharpe, J. Murphy, E. A. Espiner, C. Frampton, T. G. Yandle, and for the Australia-New Zealand Heart Failure Group Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: Prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction J. Am. Coll. Cardiol., June 1, 2001; 37(7): 1781 - 1787. [Abstract] [Full Text] [PDF] |
||||
![]() |
C Opasich, G.D Pinna, A Mazza, O Febo, R Riccardi, P.G Riccardi, S Capomolla, G Forni, F Cobelli, and L Tavazzi Six-minute walking performance in patients with moderate-to-severe heart failure; is it a useful indicator in clinical practice? Eur. Heart J., March 2, 2001; 22(6): 488 - 496. [Abstract] [PDF] |
||||
![]() |
M. A. Gaballa, A. Eckhart, W. J. Koch, and S. Goldman Vascular {beta}-adrenergic receptor system is dysfunctional after myocardial infarction Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1129 - H1135. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Galcera-Tomas, F. J. Castillo-Soria, M. Villegas-Garcia, R. Florenciano-Sanchez, J. G. Sanchez-Villanueva, J. A. N. de la Rosa, A. Martinez-Caballero, J. A. Valenti-Aldeguer, P. Jara-Perez, M. Parraga-Ramirez, et al. Effects of Early Use of Atenolol or Captopril on Infarct Size and Ventricular Volume : A Double-Blind Comparison in Patients With Anterior Acute Myocardial Infarction Circulation, February 13, 2001; 103(6): 813 - 819. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Cice, L. Ferrara, A. Di Benedetto, P. E. Russo, G. Marinelli, F. Pavese, and A. Iacono Dilated cardiomyopathy in dialysis patients--beneficial effects of carvedilol: a double-blind, placebo-controlled trial J. Am. Coll. Cardiol., February 1, 2001; 37(2): 407 - 411. [Abstract] [Full Text] [PDF] |
||||
![]() |
A.U Khand, I Gemmell, A.C Rankin, and J.G.F Cleland Clinical events leading to the progression of heart failure: insights from a national database of hospital discharges Eur. Heart J., January 2, 2001; 22(2): 153 - 164. [Abstract] [PDF] |
||||
![]() |
G. Cice, E. Tagliamonte, L. Ferrara, and A. Iacono Efficacy of carvedilol on complex ventricular arrhythmias in dilated cardiomyopathy: double-blind, randomized, placebo-controlled study Eur. Heart J., August 1, 2000; 21(15): 1259 - 1264. [Abstract] [PDF] |
||||
![]() |
A.U Khand, A.C Rankin, G.C Kaye, and J.G.F Cleland Systematic review of the management of atrial fibrillation in patients with heart failure Eur. Heart J., April 2, 2000; 21(8): 614 - 632. [Abstract] [PDF] |
||||
![]() |
M. Nagatsu, F. G. Spinale, M. Koide, H. Tagawa, G. DeFreitas, G. Cooper IV, and B. A. Carabello Bradycardia and the Role of {beta}-Blockade in the Amelioration of Left Ventricular Dysfunction Circulation, February 15, 2000; 101(6): 653 - 659. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. R. Bristow {beta}-Adrenergic Receptor Blockade in Chronic Heart Failure Circulation, February 8, 2000; 101(5): 558 - 569. [Full Text] [PDF] |
||||
![]() |
B. N. Singh Initial Antiarrhythmic Drug Therapy During Resuscitation from Sudden Cardiac Death: A Time for a Fundamental Change in Strategy? Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(1): 3 - 9. [PDF] |
||||
![]() |
S. Doshi and B. N. Singh Reducing Perioperative Cardiac Risk in Noncardiac Surgery: A Time to Delineate Simpler Strategies? Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2000; 5(2): 69 - 75. [PDF] |
||||
![]() |
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] |
||||
![]() |
A. Di Lenarda, G. Sabbadini, L. Salvatore, G. Sinagra, L. Mestroni, B. Pinamonti, D. Gregori, F. Ciani, A. Muzzi, S. Klugmann, et al. Long-term effects of carvedilol in idiopathic dilated cardiomyopathy with persistent left ventricular dysfunction despite chronic metoprolol J. Am. Coll. Cardiol., June 1, 1999; 33(7): 1926 - 1934. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. J. Cohn and W. H. Frishman Carvedilol N. Engl. J. Med., May 6, 1999; 340(18): 1443 - 1444. [Full Text] |
||||
![]() |
A P MAGGIONI and L TAVAZZI Introducing new treatments in clinical practice: the Italian approach to beta blockers in heart failure Heart, May 1, 1999; 81(5): 453 - 454. [Full Text] |
||||
![]() |
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] |
||||
![]() |
A. M. Richards, R. Doughty, M. G. Nicholls, S. Macmahon, H. Ikram, N. Sharpe, E. A. Espiner, C. Frampton, and T. G. Yandle Neurohumoral Prediction of Benefit From Carvedilol in Ischemic Left Ventricular Dysfunction Circulation, February 16, 1999; 99(6): 786 - 792. [Abstract] [Full Text] [PDF] |
||||
![]() |
H P B.-L. Rocca, D Weilenmann, F Follath, M Schlumpf, H Rickli, C Schalcher, F E Maly, R Candinas, and W Kiowski Oxygen uptake kinetics during low level exercise in patients with heart failure: relation to neurohormones, peak oxygen consumption, and clinical findings Heart, February 1, 1999; 81(2): 121 - 127. [Abstract] [Full Text] |
||||
![]() |
W. Carlson and K. Oberg Clinical Pharmacology of Carvedilol Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1999; 4(4): 205 - 218. [Abstract] [PDF] |
||||
![]() |
W. H. Frishman Carvedilol N. Engl. J. Med., December 10, 1998; 339(24): 1759 - 1765. [Full Text] [PDF] |
||||
![]() |
F. Follath, J. G. F. Cleland, W. Klein, and R. Murphy Etiology and response to drug treatment in heart failure J. Am. Coll. Cardiol., November 1, 1998; 32(5): 1167 - 1172. [Abstract] [Full Text] [PDF] |
||||
![]() |
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] |
||||
![]() |
A. Pablos-Mendez, R. G. Barr, and S. Shea Run-in Periods in Randomized Trials: Implications for the Application of Results in Clinical Practice JAMA, January 21, 1998; 279(3): 222 - 225. [Abstract] [Full Text] [PDF] |
||||
![]() |
J E Sanderson, S K W Chan, C M Yu, L Y C Yeung, W M Chan, K Raymond, K W Chan, and K S Woo beta Blockers in heart failure: a comparison of a vasodilating beta blocker with metoprolol Heart, January 1, 1998; 79(1): 86 - 92. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Lechat, S. Escolano, J. L. Golmard, H. Lardoux, S. Witchitz, J. A. Henneman, B. Maisch, M. Hetzel, P. Jaillon, J.-P. Boissel, et al. Prognostic Value of Bisoprolol-Induced Hemodynamic Effects in Heart Failure During the Cardiac Insufficiency BIsoprolol Study (CIBIS) Circulation, October 7, 1997; 96(7): 2197 - 2205. [Abstract] [Full Text] |
||||
![]() |
L. Demopoulos, M. Yeh, M. Gentilucci, M. Testa, R. Bijou, S. D. Katz, D. Mancini, M. Jones, and T. H. LeJemtel Nonselective ß-Adrenergic Blockade With Carvedilol Does Not Hinder the Benefits of Exercise Training in Patients With Congestive Heart Failure Circulation, April 1, 1997; 95(7): 1764 - 1767. [Abstract] [Full Text] |
||||
![]() |
K. Chatterjee Heart Failure Therapy in Evolution Circulation, December 1, 1996; 94(11): 2689 - 2693. [Full Text] |
||||
![]() |
M. Packer, W. S. Colucci, J. D. Sackner-Bernstein, C.-s. Liang, D. A. Goldscher, I. Freeman, M. L. Kukin, V. Kinhal, J. E. Udelson, M. Klapholz, et al. Double-Blind, Placebo-Controlled Study of the Effects of Carvedilol in Patients With Moderate to Severe Heart Failure: The PRECISE Trial Circulation, December 1, 1996; 94(11): 2793 - 2799. [Abstract] [Full Text] |
||||
![]() |
W. S. Colucci, M. Packer, M. R. Bristow, E. M. Gilbert, J. N. Cohn, M. B. Fowler, S. K. Krueger, R. Hershberger, B. F. Uretsky, J. A. Bowers, et al. Carvedilol Inhibits Clinical Progression in Patients With Mild Symptoms of Heart Failure Circulation, December 1, 1996; 94(11): 2800 - 2806. [Abstract] [Full Text] |
||||
![]() |
E. J. Eichhorn and M. R. Bristow Medical Therapy Can Improve the Biological Properties of the Chronically Failing Heart: A New Era in the Treatment of Heart Failure Circulation, November 1, 1996; 94(9): 2285 - 2296. [Abstract] [Full Text] |
||||
![]() |
M. A. Pfeffer and L. W. Stevenson {beta}-Adrenergic Blockers and Survival in Heart Failure N. Engl. J. Med., May 23, 1996; 334(21): 1396 - 1397. [Full Text] |
||||
![]() |
H. Yaoita, A. Sakabe, K. Maehara, and Y. Maruyama Different Effects of Carvedilol, Metoprolol, and Propranolol on Left Ventricular Remodeling After Coronary Stenosis or After Permanent Coronary Occlusion in Rats Circulation, February 26, 2002; 105(8): 975 - 980. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. S. Gottlieb, M. L. Fisher, J. Kjekshus, P. Deedwania, L. Gullestad, J. Vitovec, and J. Wikstrand Tolerability of {beta}-Blocker Initiation and Titration in the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) Circulation, March 12, 2002; 105(10): 1182 - 1188. [Abstract] [Full Text] [PDF] |
||||
|
Circulation Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search Copyright © 1995 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited. |