Association of Rivaroxaban vs Apixaban With Major Ischemic or Hemorrhagic Events in Patients With Atrial Fibrillation
Association of Rivaroxaban vs Apixaban With Major Ischemic or Hemorrhagic Events in Patients With Atrial Fibrillation
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DOI：
10.1001/jama.2021.21222
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发表时间：
2021-12-21
影响因子：
120.7
通讯作者：
Murray, Katherine T.
中科院分区：
文献类型：
--
作者：
Ray, Wayne A.;Chung, Cecilia P.;Murray, Katherine T.
这项队列研究评估了接受利伐沙班和阿皮沙班治疗的心房颤动的医疗保险受益者的主要缺血和出血结局。问题是，利伐沙班和阿皮沙班治疗房颤患者发生主要缺血或出血事件的风险是否存在差异？在这项包括581 451名65岁或65岁以上老年房颤患者的回顾性队列研究中，调整后的主要缺血或出血事件发生率利伐沙班为每1000人年16.1例，而阿皮沙班为每1000人年13.4例，差异有统计学意义。在患有房颤的老年人中，利伐沙班的治疗与阿匹沙班相比显著增加了主要缺血或出血事件的风险。利伐沙班和阿皮沙班是房颤患者中最常开出的口服抗凝剂，其比较有效性尚不确定。目的比较利伐沙班和阿普沙班治疗房颤患者的主要缺血和出血结局。设计、设置和参与者使用美国医疗保险受益人65岁或以上的计算机化登记和索赔文件进行的回溯性队列研究。2013年1月1日至2018年11月30日，共有581451名房颤患者开始接受利伐沙班或阿皮沙班治疗，并进行了4年的随访，直至2018年11月30日。暴露于利伐沙班(n=227 572)和阿普沙班(n=353 879)，无论是标准剂量还是减少剂量。主要结果和指标主要结果是主要的缺血性(中风/全身性栓塞)和出血性(脑内出血/其他颅内出血/致命的颅外出血)事件的组合。次要结果是非致命性颅外出血和总死亡率(致命的缺血/出血事件或随访期间的其他死亡)。比率、危险比(HR)和比率差异(RDS)根据共病的基线差异与治疗权重的反向概率进行调整。结果研究患者(平均年龄77.0岁；女性291 966例(50.2%)；接受减量治疗的134 393例(23.1%))获得474605人年的随访(中位IQR为174[62-397]天)。调整后的主要结果利伐沙班为16.1/1000人年，而阿匹沙班为13.4/1000人年(RD，2.7[95%CI，1.9-3.5]；HR，1.18[95%CI，1.12-1.24])。利伐沙班组发生重大缺血事件的风险增加(8.6比7.6/1000人年；RD，1.1[95%CI，0.5-1.7]；HR，1.12[95%CI，1.04-1.20])和出血事件(7.5比5.9/1000人年；RD，1.6[95%CI，1.1-2.1]；HR，1.26[95%CI，1.16-1.36])，包括致死性颅外出血(每1000人年1.4比1.0；RD，0.4[95%CI，0.2-0.7]；HR，1.41[95%CI，1.18-1.70])。接受利伐沙班治疗的患者发生非致命性颅外出血的风险增加(39.7比18.5每1000人年；RD，21.1[95%CI，20.0-22.3]；HR，2.07[95%CI，1.99-2.15])、致命性缺血/出血事件(4.5比3.3每1000人年；RD，1.2[95%CI，0.8-1.6]；HR，1.34[95%CI，1.21-1.48])和总死亡率(44.2比41.0/1000人年；RD，3.1[95%CI，1.8-4.5]；HR，1.06[95%CI，1.02-1.09])。在接受减少剂量(27.4比21.0每1000人年；RD，6.4[95%CI，4.1-8.7]；HR，1.28[95%CI，1.16-1.40])和标准剂量组(13.2比11.4每1000人年；RD，1.8[95%CI，1.0-2.6]；HR，1.13[95%CI，1.06-1.21])的两组患者中，主要结果的风险都增加了。结论：在65岁或65岁以上的老年医疗保险受益者中，与阿匹沙班相比，利伐沙班治疗与重大缺血或出血事件的风险显著增加相关。
This cohort study assesses major ischemic and hemorrhagic outcomes in Medicare beneficiaries with atrial fibrillation who were treated with rivaroxaban compared with apixaban.Question Is there a difference in risk of major ischemic or hemorrhagic events in patients with atrial fibrillation treated with rivaroxaban vs apixaban? Findings In this retrospective cohort study that included 581 451 patients 65 years or older enrolled in Medicare with atrial fibrillation, the adjusted incidence of major ischemic or hemorrhagic events was 16.1 per 1000 person-years for rivaroxaban vs 13.4 per 1000 person-years for apixaban, a difference that was statistically significant. Meaning Among older adults with atrial fibrillation, treatment with rivaroxaban compared with apixaban was associated with a significantly increased risk of major ischemic or hemorrhagic events.Importance The comparative effectiveness of rivaroxaban and apixaban, the most frequently prescribed oral anticoagulants for ischemic stroke prevention in patients with atrial fibrillation, is uncertain. Objective To compare major ischemic and hemorrhagic outcomes in patients with atrial fibrillation treated with rivaroxaban or apixaban. Design, Setting, and Participants Retrospective cohort study using computerized enrollment and claims files for US Medicare beneficiaries 65 years or older. Between January 1, 2013, and November 30, 2018, a total of 581 451 patients with atrial fibrillation began rivaroxaban or apixaban treatment and were followed up for 4 years, through November 30, 2018. Exposures Rivaroxaban (n = 227 572) and apixaban (n = 353 879), either standard or reduced dose. Main Outcomes and Measures The primary outcome was a composite of major ischemic (stroke/systemic embolism) and hemorrhagic (intracerebral hemorrhage/other intracranial bleeding/fatal extracranial bleeding) events. Secondary outcomes were nonfatal extracranial bleeding and total mortality (fatal ischemic/hemorrhagic event or other death during follow-up). Rates, hazard ratios (HRs), and rate differences (RDs) were adjusted for baseline differences in comorbidity with inverse probability of treatment weighting. Results Study patients (mean age, 77.0 years; 291 966 [50.2%] women; 134 393 [23.1%] receiving reduced dose) had 474 605 person-years of follow-up (median [IQR] of 174 [62-397] days). The adjusted primary outcome rate for rivaroxaban was 16.1 per 1000 person-years vs 13.4 per 1000 person-years for apixaban (RD, 2.7 [95% CI, 1.9-3.5]; HR, 1.18 [95% CI, 1.12-1.24]). The rivaroxaban group had increased risk for both major ischemic events (8.6 vs 7.6 per 1000 person-years; RD, 1.1 [95% CI, 0.5-1.7]; HR, 1.12 [95% CI, 1.04-1.20]) and hemorrhagic events (7.5 vs 5.9 per 1000 person-years; RD, 1.6 [95% CI, 1.1-2.1]; HR, 1.26 [95% CI, 1.16-1.36]), including fatal extracranial bleeding (1.4 vs 1.0 per 1000 person-years; RD, 0.4 [95% CI, 0.2-0.7]; HR, 1.41 [95% CI, 1.18-1.70]). Patients receiving rivaroxaban had increased risk of nonfatal extracranial bleeding (39.7 vs 18.5 per 1000 person-years; RD, 21.1 [95% CI, 20.0-22.3]; HR, 2.07 [95% CI, 1.99-2.15]), fatal ischemic/hemorrhagic events (4.5 vs 3.3 per 1000 person-years; RD, 1.2 [95% CI, 0.8-1.6]; HR, 1.34 [95% CI, 1.21-1.48]), and total mortality (44.2 vs 41.0 per 1000 person-years; RD, 3.1 [95% CI, 1.8-4.5]; HR, 1.06 [95% CI, 1.02-1.09]). The risk of the primary outcome was increased for rivaroxaban in both those receiving the reduced dose (27.4 vs 21.0 per 1000 person-years; RD, 6.4 [95% CI, 4.1-8.7]; HR, 1.28 [95% CI, 1.16-1.40]) and the standard dose (13.2 vs 11.4 per 1000 person-years; RD, 1.8 [95% CI, 1.0-2.6]; HR, 1.13 [95% CI, 1.06-1.21]) groups. Conclusions and Relevance Among Medicare beneficiaries 65 years or older with atrial fibrillation, treatment with rivaroxaban compared with apixaban was associated with a significantly increased risk of major ischemic or hemorrhagic events.