Long-term beta-blocker vasodilator therapy improves cardiac function in idiopathic dilated cardiomyopathy: a double-blind, randomized study of bucindolol versus placebo.
OBJECTIVE
Bucindolol is a potent nonselective beta-blocking agent with vasodilatory properties. In this study, we evaluated the effects of long-term bucindolol therapy in the treatment of heart failure from idiopathic dilated cardiomyopathy.


METHODS
Patients were eligible for enrollment if they had symptomatic heart failure, idiopathic dilated cardiomyopathy, and left ventricular ejection fraction less than 0.40. All patients received an initial test dose of 12.5 mg bucindolol orally every 12 hours for two or three doses. Patients tolerating the test dose were randomly assigned (double-blind) to receive bucindolol or placebo in a 3:2 ratio. Study medication was begun at a dose of 12.5 mg orally every 12 hours and gradually increased over a 1-month period until either a maximum tolerated dose or a target dose of 100 mg every 12 hours was reached. Study medication was then continued for an additional 2 months.


RESULTS
A total of 24 patients were enrolled into the study. Twenty-three patients tolerated bucindolol test challenge; 14 were randomized to receive bucindolol, and nine were randomly assigned to receive placebo. The placebo group (age 56 +/- 2 years) was significantly older than the bucindolol group (46 +/- 3 years), but by all other clinical and hemodynamic parameters the two groups were comparable. Twenty-two of 23 patients completed the study. Patients treated with bucindolol had significant improvements in clinical heart failure symptoms and in resting hemodynamic function, including an increase of left ventricular ejection fraction (0.26 +/- 0.02 to 0.35 +/- 0.09, p = 0.003), cardiac index (2.2 +/- 0.1 to 2.5 +/- 0.4 L/minute/m2, p = 0.014), and left ventricular stroke work index (25 +/- 3 to 35 +/- 7 g.m/m2, p = 0.002) and a decrease in pulmonary artery wedge pressure (17 +/- 3 to 10 +/- 5 mm Hg, p = 0.005) and heart rate (86 +/- 3 to 75 +/- 9 beats/minute, p = 0.012). Patients treated with bucindolol also had a significant increase in exercise left ventricular ejection fraction (0.26 +/- 0.03 to 0.32 +/- 0.14, p = 0.015) and reduction in questionnaire-measured symptoms (p = 0.007) and New York Heart Association functional class (p less than 0.001). However, total treadmill exercise duration and maximal oxygen consumption with exercise did not change. No changes in rest or exercise parameters were observed in the placebo-treated group. Central venous plasma norepinephrine concentration decreased significantly in the bucindolol-treated group (423 +/- 79 to 212 +/- 101 pg/mL, p = 0.010), but was unchanged in the placebo-treated group.


CONCLUSIONS
Bucindolol is well tolerated in patients with idiopathic dilated cardiomyopathy and congestive heart failure, and therapy for 3 months is associated with improved resting cardiac function, improved heart failure symptoms, and a reduction in venous norepinephrine concentration.
Gilbert
E M
EM
Heart Failure Treatment Program, University of Utah School of Medicine, Salt Lake City.
Anderson
J L
JL
Deitchman
D
D
Yanowitz
F G
FG
O'Connell
J B
JB
Renlund
D G
DG
Bartholomew
M
M
Mealey
P C
PC
Larrabee
P
P
Bristow
M R
MR
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006334:Heart Function Tests; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011412:Propanolamines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012129:Respiratory Function Tests; D014665:Vasodilator Agents / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D014665:Vasodilator Agents; C024307:bucindolol; D009638:Norepinephrine