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Dose-response of chronic beta-blocker treatment in heart failure from either idiopathic dilated or ischemic cardiomyopathy. Bucindolol Investigators.

AbstractBACKGROUND:
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.
AuthorsM R Bristow, J B O'Connell, E M Gilbert, W J French, G Leatherman, N E Kantrowitz, J Orie, M L Smucker, G Marshall, P Kelly
JournalCirculation (Circulation) Vol. 89 Issue 4 Pg. 1632-42 (Apr 1994) ISSN: 0009-7322 [Print] United States
PMID7908610 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Adrenergic beta-Antagonists
  • Propanolamines
  • bucindolol
Topics
  • Adrenergic beta-Antagonists (administration & dosage, therapeutic use)
  • Cardiomyopathy, Dilated (complications)
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Heart Failure (drug therapy, epidemiology, etiology)
  • Humans
  • Male
  • Middle Aged
  • Propanolamines (administration & dosage, therapeutic use)
  • Prospective Studies
  • Ventricular Function, Left (drug effects)

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