Background and Purpose:Comparative effectiveness and safety of oral anticoagulants in patients with atrial fibrillation and high polypharmacy are unknown.Methods:We used Medicare administrative data to evaluate patients with new atrial fibrillation diagnosis from 2015 to 2017, who initiated an oral anticoagulant within 90 days of diagnosis. Patients taking ≤3, 4 to 8, or ≥9 other prescription medications were categorized as having low, moderate, or high polypharmacy, respectively. Within polypharmacy categories, patients receiving apixaban 5 mg twice daily, rivaroxaban 20 mg once daily, or warfarin were matched using a 3-way propensity score matching. Study outcomes included ischemic stroke, bleeding, and all-cause mortality.Results:The study cohort included 6985 patients using apixaban, 3838 using rivaroxaban, and 6639 using warfarin. In the propensity-matched cohorts there was no difference in risk of ischemic stroke between the 3 drugs in patients with low and moderate polypharmacy. However, among patients with high polypharmacy, the risk of ischemic stroke was higher with apixaban compared with warfarin (adjusted hazard ratio 2.34 [95% CI, 1.01–5.42]; P=0.05) and similar to rivaroxaban (adjusted hazard ratio, 1.38 [95% CI, 0.67–2.84]; P=0.4). There was no difference in risk of death between the 3 drugs in patients with low and moderate polypharmacy, but apixaban was associated with a higher risk of death compared with rivaroxaban (adjusted hazard ratio, 2.03 [95% CI, 1.01–4.08]; P=0.05) in the high polypharmacy group. Apixaban had lower bleeding risk compared with warfarin in the low polypharmacy group (adjusted hazard ratio, 0.54 [95% CI, 0.32–0.90]; P=0.02), but there was no difference in bleeding between the 3 drugs in the moderate and high polypharmacy groups.Conclusions:Our study suggests that among patients with significant polypharmacy (>8 drugs), there may be a higher stroke and mortality risk with apixaban compared with warfarin and rivaroxaban. However, differences were of borderline significance.

中文翻译：

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利伐沙班，阿哌沙班和华法林在多药房颤患者中的比较疗效。

背景与目的：尚不知道口服抗凝剂在房颤和高剂量多药治疗中的有效性和安全性。方法：我们使用Medicare管理数据评估2015年至2017年新诊断为房颤的患者，他们在90天内开始口服抗凝剂诊断。服用≤3、4至8或≥9其他处方药的患者分别分类为低，中或高多药房。在多药房类别中，每天使用两次5毫克的阿哌沙班，每天一次20毫克的利伐沙班或华法林的患者使用三向倾向得分匹配进行匹配。研究结果包括缺血性中风，出血和全因死亡率。结果：该研究队列包括使用apixaban的6985例患者，使用rivaroxaban的3838例和使用华法林的6639例。在倾向匹配的人群中，低度和中度多药房患者的三种药物之间的缺血性卒中风险没有差异。然而，在高药房患者中，与华法林相比，阿哌沙班的缺血性卒中风险更高（调整后的危险比为2.34 [95％CI，1.01-5.42]；P = 0.05），与利伐沙班相似（风险比调整后为1.38 [95％CI，0.67-2.84]；P = 0.4）。低度和中度多药房患者的三种药物之间的死亡风险没有差异，但与利伐沙班相比，阿哌沙班的死亡风险更高（调整后的危险比为2.03 [95％CI，1.01-4.08]；P = 0.05）在高药房组中。与低剂量的华法林相比，阿哌沙班的出血风险更低（调整后的危险比为0.54 [95％CI，0.32-0.90]；P= 0.02），但在中度和高度综合药物治疗组中的3种药物之间的出血没有差异。结论：我们的研究表明，在具有大量综合药物治疗（> 8种药物）的患者中，卒中和死亡风险更高阿哌沙班与华法林和利伐沙班相比。但是，差异具有边界意义。