Circulation, Vol 90, 1765-1773, Copyright © 1994 by American Heart Association
BACKGROUND: Functional benefit in heart failure due to idiopathic dilated
cardiomyopathy has been observed after beta-blockade, but improvement in
survival has not been established in a large-scale randomized trial. This
was the main objective of the Cardiac Insufficiency Bisoprolol Study
(CIBIS). METHODS AND RESULTS: Six hundred forty-one patients with chronic
heart failure of various etiologies and a left ventricular ejection
fraction of < 40% entered this placebo-controlled, randomized,
double-blind study. Patients were in New York Heart Association functional
class III (95%) or IV (5%) at inclusion. All received background diuretic
and vasodilator therapy (an angiotensin-converting enzyme inhibitor in 90%
of cases). A total of 320 patients was randomized to bisoprolol and 321 to
placebo. Mean follow-up was 1.9 years. Bisoprolol was well tolerated
without between group difference in premature treatment withdrawals (82 on
placebo, 75 on bisoprolol; NS). The observed difference in mortality
between groups did not reach statistical significance: 67 patients died on
placebo, 53 on bisoprolol (P = .22; relative risk, 0.80; 95% confidence
interval, 0.56 to 1.15). No significant difference was observed in sudden
death rate (17 on placebo, 15 on bisoprolol) or death related to documented
ventricular tachycardia or fibrillation (7 on placebo, 4 on bisoprolol).
Bisoprolol significantly improved the functional status of the patients;
fewer patients in the bisoprolol group required hospitalization for cardiac
decompensation (90 on placebo versus 61 on bisoprolol, P < .01), and
more patients improved by at least one New York Heart Association
functional class (48 on placebo versus 68 on bisoprolol, P = .04) by the
end of follow-up period. CONCLUSIONS: These results confirm previous trials
evidence that a progressively increasing dose of beta-blocker in severe
heart failure confers functional benefit. Subgroup analysis suggested that
benefit from beta- blockade therapy was greater for those with nonischemic
cardiomyopathy. However, improvement in survival while on beta-blockade
remains to be demonstrated.
ARTICLES
A randomized trial of beta-blockade in heart failure. The Cardiac Insufficiency Bisoprolol Study (CIBIS). CIBIS Investigators and Committees
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G. S. Pepper and R. W. Lee Sympathetic Activation in Heart Failure and Its Treatment With {beta}-Blockade Arch Intern Med, February 8, 1999; 159(3): 225 - 234. [Abstract] [Full Text] [PDF]
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K S Spargias, A S Hall, D C Greenwood, and S G Ball beta Blocker treatment and other prognostic variables in patients with clinical evidence of heart failure after acute myocardial infarction: evidence from the AIRE study Heart, January 1, 1999; 81(1): 25 - 32. [Abstract] [Full Text]
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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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J G Crilley, J H Dark, and J A Hall Reversal of severe pulmonary hypertension with beta blockade in a patient with end stage left ventricular failure Heart, December 1, 1998; 80(6): 620 - 622. [Abstract] [Full Text]
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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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S. S. Gottlieb, R. J. McCarter, and R. A. Vogel Effect of Beta-Blockade on Mortality among High-Risk and Low-Risk Patients after Myocardial Infarction N. Engl. J. Med., August 20, 1998; 339(8): 489 - 497. [Abstract] [Full Text] [PDF]
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S R Holmer, H-W Hense, A H J Danser, B Mayer, G A J Riegger, and H Schunkert beta Adrenergic blockers lower renin in patients treated with ACE inhibitors and diuretics Heart, July 1, 1998; 80(1): 45 - 48. [Abstract] [Full Text]
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 R. M Martin, N. R Dunn, S. N Freemantle, and R. D Mann Risk of non-fatal cardiac failure and ischaemic heart disease with long acting beta 2 agonists Thorax, July 1, 1998; 53(7): 558 - 562. [Abstract] [Full Text]
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A Di Lenarda, R De Maria, A Gavazzi, D Gregori, M Parolini, G Sinagra, L Salvatore, F Longaro, E Bernobich, and F Camerini Long term survival effect of metoprolol in dilated cardiomyopathy Heart, April 1, 1998; 79(4): 337 - 344. [Abstract] [Full Text]
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T Yamada, M Fukunami, T Shimonagata, K Kumagai, J Kim, S Sanada, H Ogita, M Hori, and N Hoki Prediction of the effectiveness of long term beta blocker treatment for dilated cardiomyopathy by signal averaged electrocardiography Heart, March 1, 1998; 79(3): 256 - 261. [Abstract] [Full Text]
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R. P Steeds and K. S Channer Drug treatment in heart failure BMJ, February 14, 1998; 316(7131): 567 - 568. [Full Text]
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 S. Richard, F. Leclercq, S. Lemaire, C. Piot, and J. Nargeot Ca2+ currents in compensated hypertrophy and heart failure Cardiovasc Res, February 1, 1998; 37(2): 300 - 311. [Abstract] [Full Text] [PDF]
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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]
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R P STEEDS and K S CHANNER Heart failure: vive la difference! Heart, December 1, 1997; 78(6): 537 - 538. [Full Text] [PDF]
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S. Neubauer, M. Horn, M. Cramer, K. Harre, J. B. Newell, W. Peters, T. Pabst, G. Ertl, D. Hahn, J. S. Ingwall, et al. Myocardial Phosphocreatine-to-ATP Ratio Is a Predictor of Mortality in Patients With Dilated Cardiomyopathy Circulation, October 7, 1997; 96(7): 2190 - 2196. [Abstract] [Full Text]
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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]
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S. Basu, R. Senior, U. Raval, R. van der Does, T. Bruckner, and A. Lahiri Beneficial Effects of Intravenous and Oral Carvedilol Treatment in Acute Myocardial Infarction : A Placebo-Controlled, Randomized Trial Circulation, July 1, 1997; 96(1): 183 - 191. [Abstract] [Full Text]
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K. D. Aaronson, J. S. Schwartz, T.-M. Chen, K.-L. Wong, J. E. Goin, and D. M. Mancini Development and Prospective Validation of a Clinical Index to Predict Survival in Ambulatory Patients Referred for Cardiac Transplant Evaluation Circulation, June 17, 1997; 95(12): 2660 - 2667. [Abstract] [Full Text]
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