title: Association of treatment with carvedilol vs metoprolol succinate and mortality in patients with heart failure.
abstract: OBJECTIVE
  The β-blockers carvedilol and metoprolol succinate both reduce mortality in patients with heart failure (HF), but the comparative clinical effectiveness of these drugs is unknown.
  
  
  OBJECTIVE
  To investigate whether carvedilol is associated with improved survival compared with metoprolol succinate.
  
  
  METHODS
  Cohort study of patients with incident HF with reduced left ventricular ejection fraction (LVEF) (≤40%) who received carvedilol (n = 6026) or metoprolol succinate (n = 5638) using data from a Danish national HF registry linked with health care and administrative databases.
  
  
  METHODS
  All-cause mortality (primary outcome) and cardiovascular mortality (secondary outcome) were analyzed using Cox regression with adjustment for a propensity score, derived from a range of clinical, socioeconomic, and demographic characteristics.
  
  
  RESULTS
  The mean (SD) age of the patients was 69.3 (9.1) years, 71% were men, and 51% were hospitalized at index HF diagnosis. During a median (interquartile range) 2.4 (1.0-3.0) years of follow-up, 875 carvedilol users and 754 metoprolol users died; the cumulative incidence of mortality was 18.3% and 18.8%, respectively. The adjusted hazard ratio for carvedilol users vs metoprolol users was 0.99 (95% CI, 0.88 to 1.11), corresponding to an absolute risk difference of -0.07 (95% CI, -0.84 to 0.77) deaths per 100 person-years. Estimates were consistent across subgroup analyses by sex, age, levels of LVEF, New York Heart Association classification, and history of ischemic heart disease. A higher proportion of carvedilol users achieved the recommended daily target dose (50 mg; 3124 [52%]) than did metoprolol users (200 mg; 689 [12%]); among patients who reached the target dose, the adjusted hazard ratio was 0.97 (95% CI, 0.72-1.30). A robustness analysis with 1:1 propensity score matching confirmed the primary findings (hazard ratio, 0.97 [95% CI, 0.84-1.13]). The adjusted hazard ratio for cardiovascular mortality was 1.05 (95% CI, 0.88-1.26).
  
  
  CONCLUSIONS
  These findings from real-world clinical practice indicate that the effectiveness of carvedilol and metoprolol succinate in patients with HF is similar.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Björn
authors.initials: B
authors.lastname: Pasternak
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Svanström
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark2Department of Medicine, Stanford School of Medicine, Stanford, California.
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Hviid
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008790:Metoprolol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D016017:Odds Ratio; D011412:Propanolamines / Q000627:therapeutic use*; D057216:Propensity Score; D016016:Proportional Hazards Models; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D008790:Metoprolol