Risk of Major Gastrointestinal Bleeding With New vs Conventional Oral Anticoagulants: A Systematic Review and Meta-analysis

Clin Gastroenterol Hepatol. 2020 Apr;18(4):792-799.e61. doi: 10.1016/j.cgh.2019.05.056. Epub 2019 Jun 11.

Abstract

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.

Keywords: Clotting; Dabigatran; Stroke Prevention; Venous Thromboembolism.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Administration, Oral
  • Anticoagulants / adverse effects
  • Atrial Fibrillation* / drug therapy
  • Fibrinolytic Agents / therapeutic use
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / epidemiology
  • Humans
  • Rivaroxaban / therapeutic use
  • Stroke*

Substances

  • Anticoagulants
  • Fibrinolytic Agents
  • Rivaroxaban