BACKGROUND & AIMS There is controversy over whether use of non-vitamin K antagonist oral anticoagulants (NOACs) associates with increased risk of major gastrointestinal bleeding (GIB) compared with conventional therapies (such as vitamin K antagonists or anti-platelet agents). We performed a systematic review and meta-analysis of data from randomized controlled trials and high-quality real-world studies. METHODS We performed a systematic search of the MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov Website databases (through Oct 12, 2018) for randomized controlled trials and high-quality real-world studies that reported major GIB events in patients given NOACs or conventional therapy. Relative risks (RRs) for randomized controlled trials and adjusted hazard ratios (aHRs) for real-world studies were calculated separately using random-effects models. RESULTS We analyzed data from 43 randomized controlled trials (183,752 patients) and 41 real-world studies (1,879,428 patients). The pooled major rates of GIB for patients on NOACs (1.19%) vs conventional treatment (0.92%) did not differ significantly (RR from randomized controlled trials, 1.09; 95% CI, 0.91-1.31 and aHR from real-world studies, 1.02; 95% CI, 0.94-1.10; Pinteraction=.52). Rivaroxaban, but not other NOACs, was associated with an increased risk for major GIB (RR from randomized controlled trials, 1.39; 95% CI, 1.17-1.65 and aHR from real-world studies, 1.14; 95% CI, 1.04-1.23; Pinteraction = .06). Analyses of subgroups, such as patients with different indications, dosage, or follow-up time, did not significantly affect results. Meta-regression analysis failed to detect any potential confounding to impact the primacy outcome. CONCLUSIONS In a systematic review and meta-analysis of data from randomized controlled trials and real-world studies, we confirmed that there is no significant difference in risk of major GIB between patients receiving NOACs vs conventional treatment. Rivaroxaban users had a 39% increase in risk for major GIB.

中文翻译：

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新与传统口服抗凝剂的严重胃肠道出血风险：系统评价和荟萃分析。

背景与目的 与传统疗法（如维生素 K 拮抗剂或抗血小板剂）相比，使用非维生素 K 拮抗剂口服抗凝剂 (NOAC) 是否会增加严重胃肠道出血 (GIB) 的风险存在争议。我们对来自随机对照试验和高质量现实世界研究的数据进行了系统回顾和荟萃分析。方法 我们对 MEDLINE、EMBASE、Cochrane 图书馆和 ClinicalTrials.gov 网站数据库（截至 2018 年 10 月 12 日）进行了系统搜索，以获取报告给予 NOAC 或常规疗法。使用随机效应模型分别计算随机对照试验的相对风险 (RR) 和真实世界研究的调整风险比 (aHR)。结果 我们分析了 43 项随机对照试验（183,752 名患者）和 41 项真实世界研究（1,879,428 名患者）的数据。使用 NOAC 的患者 (1.19%) 与常规治疗 (0.92%) 的 GIB 合并主要发生率没有显着差异（随机对照试验的 RR，1.09；95% CI，0.91-1.31 和真实世界研究的 aHR，1.02 ；95% CI，0.94-1.10；Pinteraction=0.52）。利伐沙班与主要 GIB 风险增加相关（随机对照试验的 RR，1.39；95% CI，1.17-1.65；真实世界研究的 aHR，1.14；95% CI，1.04-1.23； Pinteraction = .06）。亚组分析，如具有不同适应症的患者，剂量或随访时间对结果没有显着影响。元回归分析未能检测到影响首要结果的任何潜在混杂因素。结论 在对随机对照试验和真实世界研究数据的系统评价和荟萃分析中，我们证实，接受 NOAC 与常规治疗的患者发生主要 GIB 的风险没有显着差异。利伐沙班使用者患主要 GIB 的风险增加了 39%。我们证实，接受 NOACs 与常规治疗的患者发生主要 GIB 的风险没有显着差异。利伐沙班使用者患主要 GIB 的风险增加了 39%。我们证实，接受 NOACs 与常规治疗的患者发生主要 GIB 的风险没有显着差异。利伐沙班使用者患主要 GIB 的风险增加了 39%。