Adverse effects of beta-blocker therapy for patients with heart failure: a quantitative overview of randomized trials.
BACKGROUND
Beta-blockers substantially improve survival in patients with chronic heart failure (HF) with left ventricular systolic dysfunction, but concerns about cardiovascular adverse effects may deter physicians from prescribing this therapy. We performed an overview of randomized beta-blocker trials in patients with HF to quantify the risks of these adverse effects.


METHODS
Heart failure trials of beta-blockers were identified by electronic searches of the MEDLINE database from 1966 to 2002. The random-effects model was used to combine results from individual trials and calculate estimates of risks associated with therapy.


RESULTS
beta-Blocker therapy was associated with significant absolute annual increases in risks of hypotension (11 per 1000; 95% confidence interval [CI], 0-22), dizziness (57 per 1000; 95% CI, 11-104), and bradycardia (38 per 1000; 95% CI, 21-54). There was no significant absolute risk of fatigue associated with therapy (3 per 1000; 95% CI, -2 to 9). beta-Blocker therapy was associated with a reduction in all-cause withdrawal of medication (14 per 1000; 95% CI, -2 to 29) as well as significant reductions in all-cause mortality (34 per 1000; 95% CI, 20-49), HF hospitalizations (40 per 1000; 95% CI, 22-58), and worsening HF (52 per 1000; 95% CI, 10-94).


CONCLUSIONS
Although beta-blocker therapy was associated with hypotension, dizziness, and bradycardia, the absolute increases in risk were small, and overall fewer patients were withdrawn from beta-blocker therapy than from placebo. This information should alleviate concerns about prescribing this life-saving therapy to patients with HF.
Ko
Dennis T
DT
Division of Cardiology, Schulich Heart Centre, and the Department of Medicine, Sunnybrook & Women's College Health Sciences Center, University of Toronto, Toronto, Ontario.
Hebert
Patricia R
PR
Coffey
Christopher S
CS
Curtis
Jeptha P
JP
Foody
JoAnne M
JM
Sedrakyan
Artyom
A
Krumholz
Harlan M
HM
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects*; D000368:Aged; D017298:Bisoprolol / Q000009:adverse effects; D001919:Bradycardia / Q000139:chemically induced / Q000453:epidemiology; D002227:Carbazoles / Q000009:adverse effects; D000077261:Carvedilol; D004244:Dizziness / Q000139:chemically induced / Q000453:epidemiology; D005221:Fatigue / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006329:Heart Conduction System / Q000187:drug effects / Q000473:pathology; D006333:Heart Failure / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D007022:Hypotension / Q000139:chemically induced / Q000453:epidemiology; D008297:Male; D008790:Metoprolol / Q000009:adverse effects; D008875:Middle Aged; D011412:Propanolamines / Q000009:adverse effects; D012307:Risk Factors; D040242:Risk Reduction Behavior; D012720:Severity of Illness Index; D013223:Statistics as Topic; D017211:Treatment Failure; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000453:epidemiology; D028761:Withholding Treatment
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; C024307:bucindolol; D008790:Metoprolol; D017298:Bisoprolol