title: Dose-response of chronic beta-blocker treatment in heart failure from either idiopathic dilated or ischemic cardiomyopathy. Bucindolol Investigators.
abstract: 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).
  
  
  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.
authors.affiliation: Division of Cardiology, University of Colorado Health Sciences Center, Denver 80262.
authors.forename: M R
authors.initials: MR
authors.lastname: Bristow
authors.forename: J B
authors.initials: JB
authors.lastname: O'Connell
authors.forename: E M
authors.initials: EM
authors.lastname: Gilbert
authors.forename: W J
authors.initials: WJ
authors.lastname: French
authors.forename: G
authors.initials: G
authors.lastname: Leatherman
authors.forename: N E
authors.initials: NE
authors.lastname: Kantrowitz
authors.forename: J
authors.initials: J
authors.lastname: Orie
authors.forename: M L
authors.initials: ML
authors.lastname: Smucker
authors.forename: G
authors.initials: G
authors.lastname: Marshall
authors.forename: P
authors.initials: P
authors.lastname: Kelly
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000627:therapeutic use; D002311:Cardiomyopathy, Dilated / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000008:administration & dosage* / Q000627:therapeutic use; D011446:Prospective Studies; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C024307:bucindolol