Circulation, Vol 89, 1632-1642, Copyright © 1994 by American Heart Association
MR Bristow, JB O'Connell, EM Gilbert, WJ French, G Leatherman, NE Kantrowitz, J Orie, ML Smucker, G Marshall and P Kelly
BACKGROUND: Small-scale clinical investigations have demonstrated that
single doses of beta-blocking agents can improve left ventricular function
in heart failure from idiopathic dilated cardiomyopathy (IDC). The purpose
of this multicenter clinical trial was to determine the dose-effect
characteristics of beta-blockade in a heart failure population that
includes ischemic dilated cardiomyopathy (ISCD). METHODS AND RESULTS:
Bucindolol is a nonselective beta-blocking agent with mild vasodilatory
properties. One hundred forty-one subjects with class II or III heart
failure, left ventricular ejection fraction (LVEF) < or = 0.40, and
background therapy of angiotensin-converting enzyme inhibitors, digoxin,
and diuretics were given an initial challenge dose of bucindolol 12.5 mg.
One hundred thirty-nine subjects (99 with IDC, 40 with ISCDC) tolerated
challenge and were randomized to treatment with placebo or bucindolol 12.5
mg/d (low dose), 50 mg/d (medium dose), or 200 mg/d (high dose). At the end
of 12 weeks, left ventricular function and other parameters were measured
and compared with baseline values. There was a dose-related improvement in
left ventricular function in bucindolol-treated subjects. In the high-dose
bucindolol group, radionuclide-measured LVEF improved by 7.8 EF units (%)
compared with 1.8 units in the placebo group (P < .05), and compared
with the placebo group, a greater percentage of subjects had an increase in
LVEF by > or = 5 units. In contrast, all three bucindolol doses
prevented deterioration of myocardial function as defined by an LVEF
decline of > or = 5 units. CONCLUSIONS: In heart failure from systolic
dysfunction, beta-blockade with bucindolol produces a dose-related
improvement in and prevents deterioration of left ventricular function.
ARTICLES
Dose-response of chronic beta-blocker treatment in heart failure from either idiopathic dilated or ischemic cardiomyopathy. Bucindolol Investigators
Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262.
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|
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|
|
|
|
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|
|
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|
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|
|
|
|
|
|
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|
|
|
|
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|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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]
|
|
|
|
|
|
M. R. Bristow, E. M. Gilbert, W. T. Abraham, K. F. Adams, M. B. Fowler, R. E. Hershberger, S. H. Kubo, K. A. Narahara, H. Ingersoll, S. Krueger, et al. Carvedilol Produces Dose-Related Improvements in Left Ventricular Function and Survival in Subjects With Chronic Heart Failure Circulation, December 1, 1996; 94(11): 2807 - 2816. [Abstract] [Full Text]
|
|
|
|
|
|
E. M. Gilbert, W. T. Abraham, S. Olsen, B. Hattler, M. White, P. Mealy, P. Larrabee, and M. R. Bristow Comparative Hemodynamic, Left Ventricular Functional, and Antiadrenergic Effects of Chronic Treatment With Metoprolol Versus Carvedilol in the Failing Heart Circulation, December 1, 1996; 94(11): 2817 - 2825. [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]
|
|
|
|
|
|
B. M. Massie, S. G. Fisher, P. C. Deedwania, B. N. Singh, R. D. Fletcher, and S. N. Singh Effect of Amiodarone on Clinical Status and Left Ventricular Function in Patients With Congestive Heart Failure Circulation, June 15, 1996; 93(12): 2128 - 2134. [Abstract] [Full Text]
|
|
|
|
|
|
M. Packer, M. R. Bristow, J. N. Cohn, W. S. Colucci, M. B. Fowler, E. M. Gilbert, N. H. Shusterman, and The U.S. Carvedilol Heart Failure Study Group The Effect of Carvedilol on Morbidity and Mortality in Patients with Chronic Heart Failure N. Engl. J. Med., May 23, 1996; 334(21): 1349 - 1355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Koch, C. A. Milano, and R. J. Lefkowitz Transgenic Manipulation of Myocardial G Protein–Coupled Receptors and Receptor Kinases Circ. Res., April 1, 1996; 78(4): 511 - 516. [Full Text]
|
|
|
|
|
|
M. R. Costanzo, S. Augustine, R. Bourge, M. Bristow, J. B. O'Connell, D. Driscoll, and E. Rose Selection and Treatment of Candidates for Heart Transplantation : A Statement for Health Professionals From the Committee on Heart Failure and Cardiac Transplantation of the Council on Clinical Cardiology, American Heart Association Circulation, December 15, 1995; 92(12): 3593 - 3612. [Abstract] [Full Text]
|
|
|
|
|
|
J. D. Sackner-Bernstein and D. M. Mancini Rationale for Treatment of Patients With Chronic Heart Failure With Adrenergic Blockade JAMA, November 8, 1995; 274(18): 1462 - 1467. [Abstract] [PDF]
|
|
|
|
|
|
COMMITTEE MEMBERS, J. F. WILLIAMS Jr, M. R. BRISTOW, M. B. FOWLER, G. S. FRANCIS, A. GARSON Jr, B. J. GERSH, D. F. HAMMER, M. A. HLATKY, C. V. LEIER, et al. Guidelines for the Evaluation and Management of Heart Failure : Report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on Evaluation and Management of Heart Failure) Circulation, November 1, 1995; 92(9): 2764 - 2784. [Full Text]
|
|
|
|
|
|
H. Krum, J. D. Sackner-Bernstein, R. L. Goldsmith, M. L. Kukin, B. Schwartz, J. Penn, N. Medina, M. Yushak, E. Horn, S. D. Katz, et al. Double-Blind, Placebo-Controlled Study of the Long-term Efficacy of Carvedilol in Patients With Severe Chronic Heart Failure Circulation, September 15, 1995; 92(6): 1499 - 1506. [Abstract] [Full Text]
|
|