Association of treatment with carvedilol vs metoprolol succinate and mortality in patients with heart failure.

IMPORTANCE: 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.

DESIGN, SETTING, AND PARTICIPANTS: 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.

MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: These findings from real-world clinical practice indicate that the effectiveness of carvedilol and metoprolol succinate in patients with HF is similar.