Caldeira D, Barra M, Ferreira A, Rocha A, Augusto A, Pinto F J, Costa J, Ferreira J J
Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal.
Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
Aliment Pharmacol Ther. 2015 Dec;42(11-12):1239-49. doi: 10.1111/apt.13412. Epub 2015 Oct 4.
Gastrointestinal (GI) bleeding is a common complication among anticoagulated patients. Non-vitamin K antagonist oral anticoagulants (NOACs) are associated with increased risk of GI (major and clinically relevant non-major) bleeding. However, more information is needed regarding severe events.
To evaluate the risk of NOACs major GI bleeding.
We searched for phase III randomised clinical trials (RCT) evaluating NOACs (apixaban, dabigatran, edoxaban and rivaroxaban) and reporting major GI bleeding events, in MEDLINE, Cochrane Library, SciELO collection and Web of Science databases (July 2015). Meta-analysis was performed to estimate risk ratio (RR) and 95% confidence intervals (95% CIs). Heterogeneity was assessed with the I(2) test.
A total of 23 studies were included. Among patients with atrial fibrillation, the risk of major GI bleeding was not different between NOACs and vitamin K antagonists (VKA) (RR 1.08, 95% CI 0.85-1.36, I(2) = 78%; 5 RCTs) or acetylsalicylic acid (RR 0.78, 95% CI 0.36-1.72; 1 RCT). Similar results were found for patients undergoing orthopaedic surgery and those with venous thromboembolism. NOACs were not found to increase the risk compared to low-molecular-weight heparin (LWMH) alone (RR 1.42, 95% CI 0.55-3.71, I(2) = 7%; 8 RCTs), the sequential treatment with LMWH-VKA (RR 0.77, 95% CI 0.49-1.21, I(2) = 43%; 7 RCTs) or placebo (RR 1.48, 95% CI 0.15-14.84, I(2) = 21%; 2 RCTs).
Despite previous evidence supporting the association of non-vitamin K antagonist oral anticoagulants and overall GI bleeding, non-vitamin K antagonist oral anticoagulants are not associated with increased risk of major GI bleeding compared to other anticoagulant drugs (with known increased risk of these events).
胃肠道（GI）出血是抗凝治疗患者常见的并发症。非维生素K拮抗剂口服抗凝剂（NOACs）与胃肠道（严重及具有临床意义的非严重）出血风险增加相关。然而，关于严重事件还需要更多信息。
评估NOACs导致严重胃肠道出血的风险。
我们检索了MEDLINE、Cochrane图书馆、SciELO数据库及科学网数据库（2015年7月）中评价NOACs（阿哌沙班、达比加群、依度沙班和利伐沙班）并报告严重胃肠道出血事件的III期随机临床试验（RCT）。进行荟萃分析以估计风险比（RR）和95%置信区间（95% CIs）。用I²检验评估异质性。
共纳入23项研究。在房颤患者中，NOACs与维生素K拮抗剂（VKA）相比，严重胃肠道出血风险无差异（RR 1.08，95% CI 0.85 - 1.36，I² = 78%；5项RCT）或与阿司匹林相比（RR 0.78，95% CI 0.36 - 1.72；1项RCT）。接受骨科手术的患者及静脉血栓栓塞患者也得到类似结果。与单独使用低分子肝素（LMWH）相比，未发现NOACs增加风险（RR 1.42，95% CI 0.55 - 3.71，I² = 7%；8项RCT），与LMWH - VKA序贯治疗相比（RR 0.77，95% CI 0.49 - 1.21，I² = 43%；7项RCT）或与安慰剂相比（RR 1.48，95% CI 0.15 - 14.84，I² = 21%；2项RCT）。
尽管先前有证据支持非维生素K拮抗剂口服抗凝剂与总体胃肠道出血相关，但与其他抗凝药物（已知这些事件风险增加）相比，非维生素K拮抗剂口服抗凝剂不会增加严重胃肠道出血风险。
