Influence of global region on outcomes in heart failure Beta-blocker trials.
J Am Coll Cardiol. 2011 Aug 23;58(9):915-22
Authors: O'Connor CM, Fiuzat M, Swedberg K, Caron M, Koch B, Carson PE, Gattis-Stough W, Davis GW, Bristow MR
OBJECTIVES: We sought to describe the United States and the rest of the world (ROW) outcomes from the major ?-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 ?-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 (?-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 ?-blocker was of smaller magnitude than in the overall cohort and no longer significant, whereas in the ROW subgroup, the mortality benefit for ?-blockade persisted. In the pooled analysis (n = 11,635), the RR of death was reduced by 23% (p < 0.001) with ?-blockade compared with placebo. In contrast, the mortality reduction associated with ?-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, ?-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 [PubMed - in process]