Himmelreich Jelle C L, Virdone Saverio, Camm A John, Pieper Karen, Harskamp Ralf E, Verheugt Freek W A, Bassand Jean-Pierre, Misselwitz Frank, Pereira-Barretto Antônio C, Cools Frank, Gibbs Harry, Kakkar Ajay K
Thrombosis Research Institute, London, UK
Department of General Practice, Amsterdam UMC Location AMC, Amsterdam, The Netherlands.
Open Heart. 2025 Jan 19;12(1):e002966. doi: 10.1136/openhrt-2024-002966.
This study aimed to determine the robustness, reproducibility and representativeness of the landmark Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (AF) (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in AF (ROCKET AF) randomised trials through replication in an observational AF patient registry.
Patients from the Global Anticoagulant Registry in the FIELD (GARFIELD)-AF registry treated with apixaban, rivaroxaban or vitamin K antagonist (VKA) were assessed for eligibility for the ARISTOTLE and ROCKET AF trials. HRs of apixaban and rivaroxaban versus comparator for stroke/systemic embolism, major bleeding and all-cause mortality within 2 years follow-up were calculated using propensity score overlap-weighted Cox models. Among GARFIELD-AF patients on apixaban, 2570/3615 (71%) would have been eligible for ARISTOTLE. Among patients using rivaroxaban, 2005/4914 (41%) would have been eligible for ROCKET AF. Eligibility rates were steady over time, with minor differences across medical specialties. Real-world AF patients selected according to trial criteria had lower cardiovascular burden than the original trial participants, especially compared with ROCKET AF. HRs (95% CI) for apixaban versus VKA among ARISTOTLE-eligible users were 0.57 (0.34 to 0.94) for stroke/systemic embolism, 0.76 (0.48 to 1.20) for major bleeding and 0.89 (0.70 to 1.12) for all-cause mortality. Among ROCKET AF-eligible rivaroxaban users, HRs for rivaroxaban versus VKA were 0.90 (0.57 to 1.43), 0.92 (0.59 to 1.43) and 0.86 (0.69 to 1.08), respectively. All safety and efficacy estimates were similar to those in the original trials.
Real-world representativeness of the selection criteria was greater for ARISTOTLE than ROCKET AF. The pivotal randomised trials of apixaban and rivaroxaban versus warfarin can be successfully emulated in real-world AF patients by applying trial-specific selection criteria and appropriate methodology for non-randomised treatment allocation.
NCT01090362.
本研究旨在通过在一个心房颤动（AF）患者观察性登记处进行重复研究，确定里程碑式的阿哌沙班用于降低房颤患者中风和其他血栓栓塞事件（ARISTOTLE）试验以及利伐沙班每日一次口服直接因子Xa抑制与维生素K拮抗剂用于预防房颤患者中风和栓塞试验（ROCKET AF）随机试验的稳健性、可重复性和代表性。
对全球抗凝药物注册研究（GARFIELD）-AF登记处中接受阿哌沙班、利伐沙班或维生素K拮抗剂（VKA）治疗的患者进行评估，以确定其是否符合ARISTOTLE和ROCKET AF试验的入选标准。使用倾向评分重叠加权Cox模型计算阿哌沙班和利伐沙班与对照药物相比，在2年随访期内中风/全身性栓塞、大出血和全因死亡率的风险比（HRs）。在GARFIELD-AF登记处接受阿哌沙班治疗的患者中，2570/3615（71%）符合ARISTOTLE试验的入选标准。在使用利伐沙班的患者中，2005/4914（41%）符合ROCKET AF试验的入选标准。入选率随时间保持稳定，各医学专科之间存在微小差异。根据试验标准选择的真实世界房颤患者的心血管负担低于原始试验参与者，尤其是与ROCKET AF试验相比。在符合ARISTOTLE试验入选标准的使用者中，阿哌沙班与VKA相比的HRs（95%CI）为：中风/全身性栓塞0.57（0.34至0.94），大出血0.76（0.48至1.20），全因死亡率0.89（0.70至1.12）。在符合ROCKET AF试验入选标准的利伐沙班使用者中，利伐沙班与VKA相比的HRs分别为0.90（0.57至1.43）、0.92（0.59至1.43）和0.86（0.69至1.08）。所有安全性和有效性估计值与原始试验中的相似。
ARISTOTLE试验入选标准在真实世界中的代表性高于ROCKET AF试验。通过应用特定试验的入选标准和适当的非随机治疗分配方法，可以在真实世界的房颤患者中成功模拟阿哌沙班和利伐沙班对比华法林的关键随机试验。
NCT01090362。
