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Original Investigation |

Association of Treatment With Carvedilol vs Metoprolol Succinate and Mortality in Patients With Heart Failure ONLINE FIRST

Björn Pasternak, MD, PhD1; Henrik Svanström, MSc1; Mads Melbye, MD, DrMedSci1,2; Anders Hviid, MSc, DrMedSci1
[+] Author Affiliations
1Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
2Department of Medicine, Stanford School of Medicine, Stanford, California
JAMA Intern Med. Published online August 31, 2014. doi:10.1001/jamainternmed.2014.3258
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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.

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Figure 1.
Inclusion of Carvedilol and Metoprolol Succinate Users in Study Cohort

LVEF indicates left ventricular ejection fraction.

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Figure 2.
Cumulative Incidence of All-Cause Mortality Among Patients With Heart Failure With Reduced Left Ventricular Ejection Fraction and Using Carvedilol or Metoprolol Succinate

aAdjusted for propensity score categorized in deciles.

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Figure 3.
Subgroup Analyses of All-Cause Mortality Among Patients With Heart Failure With Reduced Left Ventricular Ejection Fraction (LVEF) and Using Carvedilol or Metoprolol Succinate

NYHA indicates New York Heart Association.

aAdjusted for propensity score categorized in deciles.

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