title: Effect of Beta-Blocker Dose on Survival After Acute Myocardial Infarction.
abstract: BACKGROUND
  Beta-blocker therapy after acute myocardial infarction (MI) improves survival. Beta-blocker doses used in clinical practice are often substantially lower than those used in the randomized trials establishing their efficacy.
  
  
  OBJECTIVE
  This study evaluated the association of beta-blocker dose with survival after acute MI, hypothesizing that higher dose beta-blocker therapy will be associated with increased survival.
  
  
  METHODS
  A multicenter registry enrolled 7,057 consecutive patients with acute MI. Discharge beta-blocker dose was indexed to the target beta-blocker doses used in randomized clinical trials, grouped as >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target dose. Follow-up vital status was assessed, with the primary endpoint of time-to-death right-censored at 2 years. Multivariable and propensity score analyses were used to account for group differences.
  
  
  RESULTS
  Of 6,682 patients with follow-up (median 2.1 years), 91.5% were discharged on a beta-blocker (mean dose 38.1% of the target dose). Lower mortality was observed with all beta-blocker doses (p < 0.0002) versus no beta-blocker therapy. After multivariable adjustment, hazard ratios for 2-year mortality compared with the >50% dose were 0.862 (95% confidence interval [CI]: 0.677 to 1.098), 0.799 (95% CI: 0.635 to 1.005), and 0.963 (95% CI: 0.765 to 1.213) for the >0% to 12.5%, >12.5% to 25%, and >25% to 50% of target dose groups, respectively. Multivariable analysis with an extended set of covariates and propensity score analysis also demonstrated that higher doses were not associated with better outcome.
  
  
  CONCLUSIONS
  These data do not demonstrate increased survival in patients treated with beta-blocker doses approximating those used in previous randomized clinical trials compared with lower doses. These findings provide the rationale to re-engage in research to establish appropriate beta-blocker dosing after MI to derive optimal benefit from this therapy. (The PACE-MI Registry Study-Outcomes of Beta-blocker Therapy After Myocardial Infarction [OBTAIN]: NCT00430612).
authors.affiliation: Center for Cardiovascular Innovation and the Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. Electronic address: j-goldberger@northwestern.edu.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Goldberger
authors.affiliation: Center for Cardiovascular Innovation and the Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Bonow
authors.affiliation: Hospital Corporation of America, Brentwood, Tennessee.
authors.forename: Michael
authors.initials: M
authors.lastname: Cuffe
authors.affiliation: Department of Preventive Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: Yves
authors.initials: Y
authors.lastname: Rosenberg
authors.affiliation: Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
authors.affiliation: Heart and Vascular Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
authors.forename: Sidney C
authors.initials: SC
authors.lastname: Smith
authors.affiliation: Center for Cardiovascular Innovation and the Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Haris
authors.initials: H
authors.lastname: Subačius
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D012042:Registries; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists
keywords: adrenergic beta-antagonists; follow-up studies; registries; survival analysis