Importance Anticoagulant choice and proton pump inhibitor (PPI) cotherapy could affect the risk of upper gastrointestinal tract bleeding, a frequent and potentially serious complication of oral anticoagulant treatment. Objectives To compare the incidence of hospitalization for upper gastrointestinal tract bleeding in patients using individual anticoagulants with and without PPI cotherapy, and to determine variation according to underlying gastrointestinal bleeding risk. Design, Setting, and Participants Retrospective cohort study in Medicare beneficiaries between January 1, 2011, and September 30, 2015. Exposures Apixaban, dabigatran, rivaroxaban, or warfarin with or without PPI cotherapy. Main Outcomes and Measures Hospitalizations for upper gastrointestinal tract bleeding: adjusted incidence and risk difference (RD) per 10 000 person-years of anticoagulant treatment, incidence rate ratios (IRRs). Results There were 1 643 123 patients with 1 713 183 new episodes of oral anticoagulant treatment included in the cohort (mean [SD] age, 76.4 [2.4] years, 651 427 person-years of follow-up [56.1%] were for women, and the indication was atrial fibrillation for 870 330 person-years [74.9%]). During 754 389 treatment person-years without PPI cotherapy, the adjusted incidence of hospitalization for upper gastrointestinal tract bleeding (n = 7119) was 115 per 10 000 person-years (95% CI, 112-118). The incidence for rivaroxaban (n = 1278) was 144 per 10 000 person-years (95% CI, 136-152), which was significantly greater than the incidence of hospitalizations for apixaban (n = 279; 73 per 10 000 person-years; IRR, 1.97 [95% CI, 1.73-2.25]; RD, 70.9 [95% CI, 59.1-82.7]), dabigatran (n = 629; 120 per 10 000 person-years; IRR, 1.19 [95% CI, 1.08-1.32]; RD, 23.4 [95% CI, 10.6-36.2]), and warfarin (n = 4933; 113 per 10 000 person-years; IRR, 1.27 [95% CI, 1.19-1.35]; RD, 30.4 [95% CI, 20.3-40.6]). The incidence for apixaban was significantly lower than that for dabigatran (IRR, 0.61 [95% CI, 0.52-0.70]; RD, −47.5 [95% CI,−60.6 to −34.3]) and warfarin (IRR, 0.64 [95% CI, 0.57-0.73]; RD, −40.5 [95% CI, −50.0 to −31.0]). When anticoagulant treatment with PPI cotherapy (264 447 person-years; 76 per 10 000 person-years) was compared with treatment without PPI cotherapy, risk of upper gastrointestinal tract bleeding hospitalizations (n = 2245) was lower overall (IRR, 0.66 [95% CI, 0.62-0.69]) and for apixaban (IRR, 0.66 [95% CI, 0.52-0.85]; RD, −24 [95% CI, −38 to −11]), dabigatran (IRR, 0.49 [95% CI, 0.41-0.59]; RD, −61.1 [95% CI, −74.8 to −47.4]), rivaroxaban (IRR, 0.75 [95% CI, 0.68-0.84]; RD, −35.5 [95% CI, −48.6 to −22.4]), and warfarin (IRR, 0.65 [95% CI, 0.62-0.69]; RD, −39.3 [95% CI, −44.5 to −34.2]). Conclusions and Relevance Among patients initiating oral anticoagulant treatment, incidence of hospitalization for upper gastrointestinal tract bleeding was the highest in patients prescribed rivaroxaban, and the lowest for patients prescribed apixaban. For each anticoagulant, the incidence of hospitalization for upper gastrointestinal tract bleeding was lower among patients who were receiving PPI cotherapy. These findings may inform assessment of risks and benefits when choosing anticoagulant agents.

中文翻译：

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口服抗凝剂和质子泵抑制剂联合治疗与上消化道出血住院的关联

重要性 抗凝剂的选择和质子泵抑制剂 (PPI) 联合治疗可能会影响上消化道出血的风险，这是口服抗凝剂治疗的一种常见且潜在的严重并发症。目的 比较使用个体抗凝剂联合和未联合 PPI 的患者因上消化道出血住院的发生率，并根据潜在的消化道出血风险确定变异。设计、设置和参与者 2011 年 1 月 1 日至 2015 年 9 月 30 日期间在医疗保险受益人中进行的回顾性队列研究。阿哌沙班、达比加群、利伐沙班或华法林的暴露，有或没有 PPI 协同治疗。主要结果和措施 上消化道出血住院治疗：每 10 000 人年抗凝治疗的调整后发病率和风险差 (RD)，发病率比 (IRR)。结果 队列中包括 1 643 123 例患者和 1 713 183 次新的口服抗凝治疗发作（平均 [SD] 年龄，76.4 [2.4] 岁，随访 651 427 人年 [56.1%] 为女性） ，适应症为房颤 870 330 人年 [74.9%]）。在没有 PPI 联合治疗的 754 389 人年治疗期间，调整后的上消化道出血住院发生率（n = 7119）为每 10 000 人年 115 人（95% CI，112-118）。利伐沙班 (n = 1278) 的发生率为每 10 000 人年 144 人 (95% CI, 136-152)，显着高于阿哌沙班的住院发生率 (n = 279；每 10 000 人年 73 人) ；IRR，1.97 [95% CI，1。73-2.25]；RD，70.9 [95% CI，59.1-82.7]），达比加群（n = 629；120/10 000 人年；IRR，1.19 [95% CI，1.08-1.32]；RD，23.4 [905% CI，105% CI] -36.2]）和华法林（n = 4933；每 10 000 人年 113；IRR，1.27 [95% CI，1.19-1.35]；RD，30.4 [95% CI，20.3-40.6]）。阿哌沙班的发生率显着低于达比加群（IRR，0.61 [95% CI，0.52-0.70]；RD，-47.5 [95% CI，-60.6 至-34.3]）和华法林（IRR，0.64 [95% CI，0.57-0.73]；RD，-40.5 [95% CI，-50.0 至 -31.0]）。将 PPI 联合治疗的抗凝治疗（264 447 人年；每 10 000 人年 76 人）与没有 PPI 联合治疗的治疗进行比较时，上消化道出血住院的风险（n = 2245）总体上较低（IRR，0.66 [95 % CI，0.62-0.69]）和阿哌沙班（IRR，0.66 [95% CI，0.52-0.85]；RD，-24 [95% CI，-38 至-11]），达比加群（IRR，0.49 [95% CI，0.41-0.59]；RD，-61.1 [95% CI，-74.8 至-47.4]），利伐沙班（IRR，0.75 [95% CI，0.68-0.84]；RD，- 35.5 [95% CI，-48.6 至 -22.4]）和华法林（IRR，0.65 [95% CI，0.62-0.69]；RD，-39.3 [95% CI，-44.5 至 -34.2]）。结论及相关性在开始口服抗凝治疗的患者中，利伐沙班组上消化道出血住院率最高，阿哌沙班组最低。对于每种抗凝剂，接受 PPI 联合治疗的患者因上消化道出血住院的发生率较低。这些发现可为选择抗凝剂时的风险和益处评估提供信息。RD，-35.5 [95% CI，-48.6 至 -22.4]）和华法林（IRR，0.65 [95% CI，0.62-0.69]；RD，-39.3 [95% CI，-44.5 至 -34.2]）。结论及相关性在开始口服抗凝治疗的患者中，利伐沙班组上消化道出血住院率最高，阿哌沙班组最低。对于每种抗凝剂，接受 PPI 联合治疗的患者因上消化道出血住院的发生率较低。这些发现可为选择抗凝剂时的风险和益处评估提供信息。RD，-35.5 [95% CI，-48.6 至 -22.4]）和华法林（IRR，0.65 [95% CI，0.62-0.69]；RD，-39.3 [95% CI，-44.5 至 -34.2]）。结论及相关性在开始口服抗凝治疗的患者中，利伐沙班组上消化道出血住院率最高，阿哌沙班组最低。对于每种抗凝剂，接受 PPI 联合治疗的患者因上消化道出血住院的发生率较低。这些发现可为选择抗凝剂时的风险和益处评估提供信息。服用利伐沙班的患者因上消化道出血住院的发生率最高，服用阿哌沙班的患者最低。对于每种抗凝剂，接受 PPI 联合治疗的患者因上消化道出血住院的发生率较低。这些发现可为选择抗凝剂时的风险和益处评估提供信息。服用利伐沙班的患者因上消化道出血住院的发生率最高，服用阿哌沙班的患者最低。对于每种抗凝剂，接受 PPI 联合治疗的患者因上消化道出血住院的发生率较低。这些发现可为选择抗凝剂时的风险和益处评估提供信息。