Department of Medicine, Division of Cardiology, Division of Clinical Pharmacology, Duke University Medical Center, Durham, North Carolina, USA.
J Am Coll Cardiol. 2011 Aug 23;58(9):915-22. doi: 10.1016/j.jacc.2011.03.057.
We sought to describe the United States and the rest of the world (ROW) outcomes from the major β-blocker heart failure (HF) trials.
HF trials have demonstrated differences in outcomes by geographic region.
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.
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).
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.
我们旨在描述美国和世界其他地区（ROW）在主要β受体阻滞剂心力衰竭（HF）试验中的结局。
HF 试验已经表明了不同地区的结局存在差异。
我们纳入了随机、双盲、安慰剂对照的研究，这些研究评估了 HF 患者中的β受体阻滞剂，主要终点为死亡率，并纳入了美国患者。计算了在美国和 ROW 地区入组的患者的相对风险（RR）。采用 Cochran-Mantel-Haenszel 统计量对死亡率进行合并分析，并按研究进行分层。
MERIT-HF（美托洛尔控释片随机对照心力衰竭试验）、COPERNICUS（卡维地洛前瞻性随机累积生存试验）和 BEST（β受体阻滞剂评估生存试验）联合研究共纳入了 8988 例患者，其中 4198 例（46.7%）来自美国。在美国队列中，每种β受体阻滞剂的 RR 降低幅度小于总体队列，且不再显著，而在 ROW 亚组中，β受体阻滞剂的死亡率获益仍然存在。在汇总分析（n=11635）中，与安慰剂相比，β受体阻滞剂可降低 23%的死亡风险（p<0.001）。相比之下，在美国队列中，β受体阻滞剂与死亡率降低相关的幅度较小，且无统计学意义（RR：0.92，95%置信区间[CI]：0.82 至 1.02，p=0.11）。ROW 队列中生存获益仍然存在（RR：0.64，95%CI：0.56 至 0.72，p<0.001）。
在美国入组的患者中，β受体阻滞剂与生存率获益幅度较小相关，而 ROW 的反应与总研究人群相似。这种治疗反应的地理差异可能反映了人群差异、遗传因素、疾病管理中的文化或社会差异，或低效力和统计机会。
