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Association of Treatment With Carvedilol vs Metoprolol Succinate and Mortality in Patients With Heart Failure
Study Questions:
What is the comparative clinical effectiveness of carvedilol and metoprolol succinate in patients with heart failure (HF)?
Methods:
This was a cohort study of patients with incident HF with reduced left ventricular ejection fraction (LVEF) (≤40%) who received carvedilol (n = 6,026) or metoprolol succinate (n = 5,638) using data from a Danish national HF registry linked with health care and administrative databases. The main outcomes and measures were all-cause mortality (primary outcome) and cardiovascular mortality (secondary outcome), which were analyzed using Cox regression with adjustment for a propensity score, derived from a range of clinical, socioeconomic, and demographic characteristics.
Results:
The mean (standard deviation) 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 versus metoprolol users was 0.99 (95% confidence interval [CI], 0.88-1.11), 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; 3,124 [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:
The authors concluded that the effectiveness of carvedilol and metoprolol succinate in patients with HF is similar.
Perspective:
In this large contemporary national cohort study of patients with HF with reduced LVEF, there was no significant difference in all-cause mortality between carvedilol and metoprolol succinate users. The primary findings were consistent through various analyses, including the secondary outcome of cardiovascular mortality, key subgroups, and robustness analyses. Given the limits of the CIs, this study could rule out a relative difference in mortality of more than 12%, and an absolute difference of one death or more per 100 patient-years. This suggests that any difference between carvedilol and metoprolol succinate, if it exists, is unlikely to be clinically meaningful. The data support current guideline recommendations, which do not explicitly support the use of one beta-blocker with proven mortality benefit in HF over the other, and thereby regard the effectiveness of these drugs as equivalent.
Keywords: Myocardial Ischemia, Carbazoles, Heart Failure, Stroke Volume, Propanolamines, Metoprolol, ESC Congress
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