title: Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure.
abstract: BACKGROUND
  Guidelines recommend that patients with heart failure receive beta-blockers in doses used in the trials that have proven their efficacy. Although the adverse effects of beta-blockade are dose-related, it is unclear whether the benefits are.
  
  
  OBJECTIVE
  To determine whether the survival benefits of beta-blockade in heart failure are associated with the magnitude of heart rate reduction or the beta-blocker dose.
  
  
  METHODS
  MEDLINE, EMBASE, CINAHL, SIGLE, Web of Science, and the Cochrane Central Register of Controlled Trials, supplemented by hand-searches of bibliographies.
  
  
  METHODS
  Randomized, placebo-controlled heart failure trials that reported all-cause mortality.
  
  
  METHODS
  Two reviewers independently extracted data on study characteristics, beta-blocker dosing and heart rate reduction, and death.
  
  
  RESULTS
  The mean left ventricular ejection fraction in the 23 beta-blocker trials ranged from 0.17 to 0.36, and more than 95% of the 19 209 patients had systolic dysfunction. The overall risk ratio for death was 0.76 (95% CI, 0.68 to 0.84); however, heterogeneity testing revealed moderate heterogeneity among trials (I (2) = 30%), which was associated with the magnitude of heart rate reduction achieved within each trial (P for meta-regression = 0.006). For every heart rate reduction of 5 beats/min with beta-blocker treatment, a commensurate 18% reduction (CI, 6% to 29%) in the risk for death occurred. No significant relationship between all-cause mortality and beta-blocker dosing was observed (risk ratio for death, 0.74 [CI, 0.64 to 0.86]) in high-dose beta-blocker trials vs. 0.78 [CI, 0.63 to 0.96] in low-dose beta-blocker trials; P for meta-regression = 0.69).
  
  
  CONCLUSIONS
  The analysis is based on aggregate data and resting heart rates. Few patients in these trials had bradycardia or diastolic dysfunction at baseline.
  
  
  CONCLUSIONS
  The magnitude of heart rate reduction is statistically significantly associated with the survival benefit of beta-blockers in heart failure, whereas the dose of beta-blocker is not.
authors.affiliation: University of Alberta Hospital, 2F1.21 Walter Mackenzie Health Sciences Centre, 8440 112 Street, Edmonton, Alberta, Canada. finlay.mcalister@ualberta.ca
authors.forename: Finlay A
authors.initials: FA
authors.lastname: McAlister
authors.forename: Natasha
authors.initials: N
authors.lastname: Wiebe
authors.forename: Justin A
authors.initials: JA
authors.lastname: Ezekowitz
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Leung
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D002423:Cause of Death; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D000319:Adrenergic beta-Antagonists