Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Scottsdale, Arizona; Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota; Division of Health Care Policy and Research, Mayo Clinic, Rochester, Minnesota.
Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, Minnesota; Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota.
Gastroenterology. 2017 Apr;152(5):1014-1022.e1. doi: 10.1053/j.gastro.2016.12.018. Epub 2016 Dec 30.
BACKGROUND & AIMS: Direct oral anticoagulant (DOAC) agents increase the risk of gastrointestinal (GI) bleeding. We investigated which DOAC had the most favorable GI safety profile and compared differences among these drugs in age-related risk of GI bleeding.
We conducted a retrospective, propensity-matched study using administrative claims data from the OptumLabs Data Warehouse of privately insured individuals and Medicare Advantage enrollees. We created 3 propensity-matched cohorts of patients with non-valvular atrial fibrillation with incident exposure to dabigatran, rivaroxaban, or apixaban from October 1, 2010 through February 28, 2015. We compared data on rivaroxaban vs dabigatran for 31,574 patients, data on apixaban vs dabigatran for 13,084 patients, and data on apixaban vs rivaroxaban for 13,130 patients. Cox proportional hazards models, stratified by age, were used to estimate rates of total GI bleeding.
Baseline characteristics were well balanced among sub-cohorts. GI bleeding occurred more frequently in patients given rivaroxaban than dabigatran (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.00-1.45). Apixaban was associated with a lower risk of GI bleeding than dabigatran (HR, 0.39; 95% CI, 0.27-0.58; P < .001) or rivaroxaban (HR, 0.33; 95% CI, 0.22-0.49; P < .001). Rates of events for all DOACs increased among patients 75 years or older. Apixaban had a lower risk of association with GI bleeding in the very elderly than dabigatran (HR, 0.45; 95% CI, 0.29-0.71) or rivaroxaban (HR, 0.39; 95% CI, 0.25-0.61). Median times to GI bleeding were <90 days for apixaban and rivaroxaban and <120 days for dabigatran.
In a population-based study of patients receiving DOAC agents, we found apixaban had the most favorable GI safety profile and rivaroxaban the least favorable profile. GI bleeding events among patient aged 75 years or older taking DOACs increased with age; the risk was greatest among persons 75 years. Apixaban had the most favorable GI safety profile among all age groups.
直接口服抗凝剂（DOAC）会增加胃肠道（GI）出血的风险。我们研究了哪种 DOAC 具有最有利的胃肠道安全性，并比较了这些药物在与年龄相关的胃肠道出血风险方面的差异。
我们使用 OptumLabs 数据仓库中私人保险个人和医疗保险优势参保者的行政索赔数据，进行了一项回顾性、倾向评分匹配研究。我们从 2010 年 10 月 1 日至 2015 年 2 月 28 日创建了 3 个具有非瓣膜性心房颤动的倾向评分匹配队列，这些患者发生了达比加群、利伐沙班或阿哌沙班的新暴露。我们比较了 31574 例患者中利伐沙班与达比加群的数据、13084 例患者中阿哌沙班与达比加群的数据，以及 13130 例患者中阿哌沙班与利伐沙班的数据。使用按年龄分层的 Cox 比例风险模型来估计总胃肠道出血的发生率。
亚队列之间的基线特征平衡良好。与达比加群相比，给予利伐沙班的患者胃肠道出血更常见（风险比 [HR]，1.20；95%置信区间 [CI]，1.00-1.45）。与达比加群（HR，0.39；95%CI，0.27-0.58；P<0.001）或利伐沙班（HR，0.33；95%CI，0.22-0.49；P<0.001）相比，阿哌沙班与胃肠道出血风险降低相关。所有 DOAC 患者的事件发生率均随年龄增长而增加。与达比加群（HR，0.45；95%CI，0.29-0.71）或利伐沙班（HR，0.39；95%CI，0.25-0.61）相比，阿哌沙班在高龄患者中与胃肠道出血的关联风险较低。阿哌沙班和利伐沙班的胃肠道出血中位时间<90 天，达比加群<120 天。
在一项接受 DOAC 药物治疗的患者的基于人群的研究中，我们发现阿哌沙班具有最有利的胃肠道安全性，而利伐沙班的安全性最差。服用 DOAC 的 75 岁或以上患者的胃肠道出血事件随年龄增长而增加；风险最大的是 75 岁的患者。在所有年龄组中，阿哌沙班的胃肠道安全性最佳。
