Centre d'Investigations Cliniques Plurithématique, Université de Lorraine, Inserm 1433, Nancy, France, Centre Hospitalier Régional Universitaire (CHRU) de Nancy, Inserm U1116, Nancy, France, French Clinical Research Infrastructure Network Investigation Network Initiative - Cardiovascular and Renal Clinical Trialists, Nancy, France.
Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, Scotland.
JACC Heart Fail. 2021 Mar;9(3):201-211. doi: 10.1016/j.jchf.2020.11.007. Epub 2021 Feb 3.
This study sought to compare patient characteristics, outcomes, and treatment effects among regions in the COMMANDER-HF trial.
Globalization of cardiovascular trials increases generalizability. However, regional differences may also introduce heterogeneity in results.
Incidence rates and interactions with treatment were recorded in pre-specified regions: Eastern Europe, Western Europe and South Africa, North America, Asia-Pacific, and Latin America.
Most patients (n = 3,224; 64.2%) were from Eastern Europe; 458 (9.1%) were from Western Europe and South Africa; 149 (3.0%) were from North America; 733 (14.6%) were from Asia-Pacific; and 458 (9.1%) were from Latin America. Compared with patients from Eastern Europe, patients from Western Europe and South Africa, North America, and Asia-Pacific were older and more likely to have coronary interventions and cardiac devices. Patients from Eastern Europe had the lowest event rates. For the primary outcome of myocardial infarction (MI), stroke, or all-cause death, event rates (100/year) were 11.6 in Eastern Europe (10.8 to 12.5); 19.5 (16.5 to 23.0) in Western Europe and South Africa; 14.2 (10.5 to 19.2) in North America; 17.7 (15.4 to 20.3) in Asia-Pacific; and 18.6 (15.6 to 22.1) in Latin America. There was a lower incidence of bleeding in Eastern Europe. Blood concentrations of rivaroxaban (Xarelto, Titusville, New Jersey) at 4 weeks were undetectable in 21% patients from Eastern Europe (n = 128) compared to 5% in other regions (n = 42). There was no evidence of treatment-by-region heterogeneity for the primary outcome (interaction = 0.14), but a favorable effect on the secondary outcome of MI, stroke, or cardiovascular death was observed in Western Europe and South Africa, North America, and Latin America but not in Eastern Europe and Asia-Pacific (interaction = 0.017).
In the COMMANDER-HF study, patients from Eastern Europe had a lower risk profile and fewer cardiovascular and bleeding events, possibly related to lower treatment adherence. Those differences might have influenced the effect of rivaroxaban therapy. (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction or Stroke in Participants With Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure [COMMANDER HF]; NCT01877915).
本研究旨在比较 COMMANDER-HF 试验中各地区的患者特征、结局和治疗效果。
心血管试验全球化可提高结果的普遍性。但区域差异也可能导致结果存在异质性。
在预先指定的地区记录发生率和与治疗的相互作用：东欧、西欧和南非、北美、亚太地区和拉丁美洲。
大多数患者（n=3224；64.2%）来自东欧；458 例（9.1%）来自西欧和南非；149 例（3.0%）来自北美；733 例（14.6%）来自亚太地区；458 例（9.1%）来自拉丁美洲。与来自东欧的患者相比，来自西欧和南非、北美和亚太地区的患者年龄更大，更有可能接受冠状动脉介入治疗和心脏设备治疗。来自东欧的患者事件发生率最低。对于心肌梗死（MI）、中风或全因死亡的主要结局，事件发生率（每年 100 例）在东欧为 11.6（10.8 至 12.5）；在西欧和南非为 19.5（16.5 至 23.0）；在北美为 14.2（10.5 至 19.2）；在亚太地区为 17.7（15.4 至 20.3）；在拉丁美洲为 18.6（15.6 至 22.1）。东欧的出血发生率较低。在接受 Rivaroxaban（Xarelto，新泽西州 Titusville）治疗的 4 周时，来自东欧的 21%（n=128）患者的 Rivaroxaban 血药浓度无法检测到，而其他地区（n=42）的血药浓度为 5%。主要结局无治疗-地区异质性证据（交互作用=0.14），但在西欧和南非、北美和拉丁美洲观察到 MI、中风或心血管死亡的次要结局有获益，但在东欧和亚太地区没有（交互作用=0.017）。
在 COMMANDER-HF 研究中，来自东欧的患者风险状况较低，心血管和出血事件较少，可能与较低的治疗依从性有关。这些差异可能影响了 Rivaroxaban 治疗的效果。（一项评估 Rivaroxaban 在心力衰竭和冠状动脉疾病患者因失代偿性心力衰竭发作后降低死亡、心肌梗死或中风风险的有效性和安全性的研究[COMMANDER HF]；NCT01877915）。
