Epidemiology and Benefit Risk, Sanofi U.S.,Bridgewater, New Jersey.
Department of Medicine, Division of Cardiology, Columbia University, New York, USA.
Am J Cardiol. 2021 Nov 15;159:79-86. doi: 10.1016/j.amjcard.2021.08.015.
Dronedarone may increase exposure and the risk of major bleeding when prescribed with a direct oral anticoagulant (DOAC). This retrospective cohort study examined the risk of the first occurrence of major bleeding (hospitalization or emergency room visit for gastrointestinal [GI] bleeding, intracranial hemorrhage [ICH], or bleeding at other sites) among new users of apixaban, dabigatran, and rivaroxaban in patients with AF ≥18 years (January 1, 2007 to September 30, 2017) from the United States Truven Health MarketScan claims, comparing concomitant users of dronedarone to DOAC alone users in patients with atrial fibrillation (AF). No increased risk of major bleeding was associated with use of dronedarone and apixaban (adjusted Hazard Ratio [aHR]: 0.69 [95% confidence interval [CI]: 0.40, 1.17], p = 0.16), a modestly increased risk of GI bleeding but not overall bleeding was associated with use of dronedarone and dabigatran (aHR bleeding: 1.18 [95% CI: 0.89, 1.56], p = 0.26; aHR GI bleeding: 1.40 [95% CI: 1.01, 1.93]; p = 0.04) and an increased risk of overall bleeding, driven by GI bleeding, was associated with use of dronedarone and rivaroxaban (aHR bleeding: 1.31 [95% CI: 1.01, 1.69]; p = 0.04; aHR GI bleeding: 1.39 [95% CI: 0.98, 1.95]; p = 0.06), compared to each DOAC respectively. There was no increased risk of ICH associated with combined use of dronedarone and any DOAC. Prospective analyses, preferably randomized controlled studies, are needed to further explore the risk of major bleeding with concomitant use of DOACs and CYP3A4/P-gp inhibitors such as dronedarone.
当与直接口服抗凝剂 (DOAC) 一起使用时，决奈达隆可能会增加暴露量和大出血的风险。这项回顾性队列研究检查了新使用阿哌沙班、达比加群和利伐沙班的患者（年龄≥ 18 岁，AF）中首次发生大出血（住院或因胃肠道 [GI] 出血、颅内出血 [ICH] 或其他部位出血而急诊就诊）的风险，比较了在 AF 患者中同时使用决奈达隆与单独使用 DOAC 的患者。与使用阿哌沙班联合决奈达隆相比，使用决奈达隆与阿哌沙班联合使用不会增加大出血的风险（调整后的危险比 [aHR]：0.69 [95%置信区间 [CI]：0.40，1.17]，p=0.16），使用决奈达隆与达比加群联合使用时 GI 出血但总出血风险适度增加（出血 aHR：1.18 [95% CI：0.89，1.56]，p=0.26；GI 出血 aHR：1.40 [95% CI：1.01，1.93]；p=0.04），使用决奈达隆与利伐沙班联合使用时总出血风险增加，主要由 GI 出血引起（出血 aHR：1.31 [95% CI：1.01，1.69]；p=0.04；GI 出血 aHR：1.39 [95% CI：0.98，1.95]；p=0.06），与每种 DOAC 相比。与联合使用 DOAC 和 CYP3A4/P-gp 抑制剂（如决奈达隆）相比，联合使用决奈达隆和任何 DOAC 均不会增加 ICH 的风险。需要进行前瞻性分析，最好是随机对照研究，以进一步探讨同时使用 DOAC 和 CYP3A4/P-gp 抑制剂（如决奈达隆）时大出血的风险。
