BACKGROUND The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin. METHODS The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models. RESULTS Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11-2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16-2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome. CONCLUSIONS A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.

中文翻译：

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房颤患者在ARISTOTLE试验中服用非甾体类抗炎药和口服抗凝药。

背景技术将非甾体抗炎药（NSAID）与口服抗凝剂一起使用已增加了出血的风险。我们调查了服用NSAIDs和阿哌沙班或华法林的房颤患者的出血风险和主要的心血管结局。方法ARISTOTLE试验（阿哌沙班减少心房纤颤中风和其他血栓栓塞事件； n = 18 201）比较了阿哌沙班和华法林对卒中风险增加的心房纤颤患者的影响。这项分析包括ARISTOTLE且无严重肾病（肌酐清除率≤30 mL / min）或肝病的患者（n = 17 423）。基线时使用NSAID，试验期间使用NSAID（事件NSAID使用），从未描述用户。主要结局是大出血。次要结果包括临床相关的非重大出血，胃肠道出血，心力衰竭住院，中风或全身性栓塞和全因死亡率。使用时间依赖性Cox比例风险模型分析了试验期间NSAID的使用以及随机治疗之间的相互作用。结果那些使用基线NSAID的患者（n = 832 [4.8％]），使用NSAID的事件（n = 2185 [13.2％]），并且从未使用过类似的中位数年龄（年龄[25、75]； 70 [64、77]） ]对70 [63，75]对70 [62，76]）。基线时使用NSAID并使用NSAID的患者比从未使用过的患者更容易有出血史（分别为24.5％，21.0％和15.6％）。在1.8（1.4，2.3）年的中位随访期（第25、75）中，如果不包括基线时服用NSAID的患者，我们发现，使用非甾体抗炎药会增加大出血风险（危险比[HR]，1.61 [95％CI，1.11-2.33]）和临床上相关的非大出血风险（HR，1.70 [95％CI，1.16-2.48] ]），但不消化道出血。对于任何结局，在使用NSAID和随机治疗之间均未观察到明显的相互作用。结论ARISTOTLE试验中大量患者服用了NSAID。使用非甾体抗炎药事件与重大和临床相关的非重大出血有关，但与胃肠道出血无关。非甾体抗炎药使用阿哌沙班与华法林的安全性和疗效似乎没有明显改变。这项研究值得进一步研究NSAID对阿哌沙班治疗患者的预后的影响。临床试验注册网址：https：//www.clinicaltrials.gov。唯一标识符：