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(Circulation. 2000;102:546.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Differential Effects of ß-Blockers in Patients With Heart Failure
A Prospective, Randomized, Double-Blind Comparison of the Long-Term Effects of Metoprolol Versus Carvedilol
From the Cattedra di Cardiologia, Università di Brescia, Italy (M.M., S.N., E.B., L.D.C.); Servizio di Medicina Nucleare, Spedali Civili di Brescia, Italy (R.G.); and Cattedra di Cardiologia, Università di Modena, Italy (M.G.M.).
Correspondence to Dr Marco Metra, Cattedra di Cardiologia, c/o Spedali Civili, P.zza Spedali Civili, 25100 Brescia, Italy. E-mail metramarco{at}libero.it
Background—Both metoprolol and carvedilol produce hemodynamic and clinical benefits in patients with chronic heart failure; carvedilol exerts greater antiadrenergic effects than metoprolol, but it is unknown whether this pharmacological difference results in hemodynamic and clinical differences between the 2 drugs.
Methods and Results—We randomized 150 patients with heart failure
(left ventricular ejection fraction 
0.35) to double-blind
treatment with either metoprolol or carvedilol. When compared with
metoprolol (124±55 mg/d), patients treated with carvedilol (49±18
mg/d) showed larger increases in left ventricular ejection
fraction at rest (+10.9±11.0 versus +7.2±7.7 U,
P=0.038) and in left ventricular stroke
volume and stroke work during exercise (both P<0.05)
after 13 to 15 months of treatment. In addition, carvedilol produced
greater decreases in mean pulmonary artery pressure and
pulmonary wedge pressure, both at rest and during exercise,
than metoprolol (all P<0.05). In contrast, the
metoprolol group showed greater increases in maximal exercise capacity
than the carvedilol group (P=0.035), but the 2 drugs
improved symptoms, submaximal exercise tolerance, and quality of life
to a similar degree. After a mean of 23±11 months of follow-up, 21
patients in the metoprolol group and 17 patients in the carvedilol
group died or underwent urgent transplantation.
Conclusions—The present study demonstrates that during long-term therapy, carvedilol improves cardiac performance to a greater extent than metoprolol when administered to patients with heart failure in the doses shown to be effective in clinical trials. These differences were likely related to a greater antiadrenergic activity of carvedilol.
Key Words: heart failure • receptors, adrenergic, beta • hemodynamics
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 S. Goldstein Benefits of {beta}-Blocker Therapy for Heart Failure: Weighing the Evidence Arch Intern Med, March 25, 2002; 162(6): 641 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. A. Victal, J. R. Teerlink, E. Gaxiola, A. W. Wallace, S. Najar, D. H. Camacho, A. Gutierrez, G. Herrera, G. Zuniga, F. Mercado-Rios, et al. Left Ventricular Volume Reduction by Radiofrequency Heating of Chronic Myocardial Infarction in Patients With Congestive Heart Failure Circulation, March 19, 2002; 105(11): 1317 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Stoschitzky Beta-blockers in chronic heart failure Eur. Heart J., March 1, 2002; 23(5): 426 - 426. [Full Text] [PDF]
|
|
|
|
|
|
W. Remme and K. Swedberg A reply Eur. Heart J., March 1, 2002; 23(5): 426 - 427. [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
C. Leclercq and D. A. Kass Retiming the failing heart: principles and current clinical status of cardiac resynchronization J. Am. Coll. Cardiol., January 16, 2002; 39(2): 194 - 201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Mak and G. E. Newton The Oxidative Stress Hypothesis of Congestive Heart Failure : Radical Thoughts Chest, December 1, 2001; 120(6): 2035 - 2046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Azevedo, T. Kubo, S. Mak, A. Al-Hesayen, A. Schofield, R. Allan, S. Kelly, G. E. Newton, J. S. Floras, and J. D. Parker Nonselective Versus Selective {beta}-Adrenergic Receptor Blockade in Congestive Heart Failure: Differential Effects on Sympathetic Activity Circulation, October 30, 2001; 104(18): 2194 - 2199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Maack, T. Elter, G. Nickenig, K. LaRosee, M. Crivaro, A. Stablein, H. Wuttke, and M. Bohm Prospective crossover comparison of carvedilol and metoprolol in patients with chronic heart failure J. Am. Coll. Cardiol., October 1, 2001; 38(4): 939 - 946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Task Force for the Diagnosis and Treatment of Chro, W. J. Remme, and K. Swedberg Guidelines for the diagnosis and treatment of chronic heart failure Eur. Heart J., September 1, 2001; 22(17): 1527 - 1560. [PDF]
|
|
|
|
|
|
X.-L. Ma, F. Gao, A. H. Nelson, B. L. Lopez, T. A. Christopher, T.-L. Yue, and F. C. Barone Oxidative Inactivation of Nitric Oxide and Endothelial Dysfunction in Stroke-Prone Spontaneous Hypertensive Rats J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 879 - 885. [Abstract] [Full Text]
|
|
|
|
|
|
R. A. De Boer, D. J. Van Veldhuisen, M. Metra, R. Giubbini, S. Nodari, E. Boldi, M. Grazia Modena, and L. Dei Cas {beta}-Blockade in Chronic Heart Failure Response Circulation, June 12, 2001; 103 (23): e118 - e118. [Full Text] [PDF]
|
|
|
|
 |
|
 Carvedilol Beats Metoprolol for Cardiac Performance in Heart Failure Journal Watch Cardiology, October 13, 2000; 2000(1013): 2 - 2. [Full Text]
|
|
|
|
|
|
M. R. Bristow What Type of {beta}-Blocker Should Be Used to Treat Chronic Heart Failure? Circulation, August 1, 2000; 102(5): 484 - 486. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|