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J Am Coll Cardiol. 2011 Aug 23;58(9):915-22. doi: 10.1016/j.jacc.2011.03.057.

Influence of global region on outcomes in heart failure β-blocker trials.

Author information

1
Department of Medicine, Division of Cardiology, Division of Clinical Pharmacology, Duke University Medical Center, Durham, North Carolina, USA. oconn002@mc.duke.edu

Abstract

OBJECTIVES:

We sought to describe the United States and the rest of the world (ROW) outcomes from the major β-blocker heart failure (HF) trials.

BACKGROUND:

HF trials have demonstrated differences in outcomes by geographic region.

METHODS:

Randomized, double-blind, placebo-controlled studies that evaluated β-blockers in HF patients, had a primary endpoint of mortality, and enrolled U.S. patients were included. Relative risk (RR) was calculated for patients enrolled in the United States and ROW. Meta-analysis of the combined mortality rates was performed using the Cochran-Mantel-Haenszel statistic, stratified by study.

RESULTS:

A total of 8,988 patients were enrolled in the MERIT-HF (Metoprolol Controlled-Release Randomized Intervention Trial in Heart Failure), COPERNICUS (Carvedilol Prospective Randomized Cumulative Survival trial), and BEST (β-Blocker Evaluation of Survival Trial) combined; 4,198 (46.7%) were from the United States. In the U.S. cohort, the RR reduction for each β-blocker was of smaller magnitude than in the overall cohort and no longer significant, whereas in the ROW subgroup, the mortality benefit for β-blockade persisted. In the pooled analysis (n = 11,635), the RR of death was reduced by 23% (p < 0.001) with β-blockade compared with placebo. In contrast, the mortality reduction associated with β-blockade in the U.S. cohort was small and not statistically significant (RR: 0.92, 95% confidence interval [CI]: 0.82 to 1.02, p = 0.11). The survival benefit persisted in the ROW cohort (RR: 0.64, 95% CI: 0.56 to 0.72, p < 0.001).

CONCLUSIONS:

Among patients enrolled in the United States, β-blockade was associated with a lower magnitude of survival benefit, whereas the ROW response was similar to the total study population. This geographic difference in treatment response may be a reflection of population differences, genetics, cultural or social differences in disease management, or low power and statistical chance.

PMID:
21851879
DOI:
10.1016/j.jacc.2011.03.057
[Indexed for MEDLINE]
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