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.
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.
Authors: Jacob P Kelly; Robert J Mentz; Alexandre Mebazaa; Adriaan A Voors; Javed Butler; Lothar Roessig; Mona Fiuzat; Faiez Zannad; Bertram Pitt; Christopher M O'Connor; Carolyn S P Lam Journal: J Am Coll Cardiol Date: 2015-04-28 Impact factor: 24.094
Authors: Matthew E Harinstein; Javed Butler; Stephen J Greene; Gregg C Fonarow; Norman L Stockbridge; Christopher M O'Connor; Marc A Pfeffer; Mandeep R Mehra; Scott D Solomon; Clyde W Yancy; Mona Fiuzat; Robert J Mentz; Sean P Collins; John J V McMurray; Muthiah Vaduganathan; Preston M Dunnmon; Giuseppe M C Rosano; Wilfried Dinh; Frank Misselwitz; Robert O Bonow; Mihai Gheorghiade Journal: Heart Fail Rev Date: 2015-07 Impact factor: 4.214
Authors: Robert J Mentz; Lothar Roessig; Barry H Greenberg; Naoki Sato; Kaori Shinagawa; Daniel Yeo; Bernard W K Kwok; Eugenio B Reyes; Henry Krum; Burkert Pieske; Stephen J Greene; Andrew P Ambrosy; Jacob P Kelly; Faiez Zannad; Bertram Pitt; Carolyn S P Lam Journal: JACC Heart Fail Date: 2016-06 Impact factor: 12.035
Authors: Robert J Mentz; Gad Cotter; John G F Cleland; Susanna R Stevens; Karen Chiswell; Beth A Davison; John R Teerlink; Marco Metra; Adriaan A Voors; Liliana Grinfeld; Mikhail Ruda; Viacheslav Mareev; Chaim Lotan; Daniel M Bloomfield; Mona Fiuzat; Michael M Givertz; Piotr Ponikowski; Barry M Massie; Christopher M O'Connor Journal: Eur J Heart Fail Date: 2014-04-25 Impact factor: 15.534
Authors: Alicia Mecklai; Haris Subačius; Marvin A Konstam; Mihai Gheorghiade; Javed Butler; Andrew P Ambrosy; Stuart D Katz Journal: JACC Heart Fail Date: 2016-03-30 Impact factor: 12.035