The association between non-vitamin K antagonist oral anticoagulants and gastrointestinal bleeding: a meta-analysis of observational studies

Abstract

Particular concerns have been raised regarding the association between non-vitamin K antagonist oral anticoagulants (NOACs) and the risk of gastrointestinal bleeding (GIB); however, current findings are still inconclusive. We conducted a systematic review with a meta-analysis to examine the association between NOACs and GIB in real-life settings. We performed a systematic search of PubMed, EMBASE and CINAHL Plus up to September 2015. Observational studies that evaluated exposure to NOACs reporting GIB outcomes were included. The inverse variance method using the random-effects model was used to calculate the pooled estimates. Eight cohort studies were included in the primary meta-analysis, enrolling 1442 GIB cases among 106 626 dabigatran users (49 486 patient-years), and 184 GIB cases among 10 713 rivaroxaban users (4046 patient-years). The pooled incidence rates of GIB were 4.50 [95% confidence interval (CI) 3.17, 5.84] and 7.18 (95% CI 2.42, 12.0) per 100 patient-years among dabigatran and rivaroxaban users, respectively. The summary risk ratio (RR) was 1.21 (95% CI 1.05, 1.39) for dabigatran compared with warfarin, and 1.09 (95% CI 0.92, 1.30) for rivaroxaban. Subgroup analyses showed a dose-related effect of dabigatran, with a significantly higher risk of GIB for 150 mg b.i.d. (RR = 1.51, 95% CI 1.34, 1.70) but not for 75 mg b.i.d. or 110 mg b.i.d.. In addition, the use of proton pump inhibitors (PPIs)/histamine H2-receptor antagonists (H2RAs) influenced the association in dabigatran users, whereas this effect was modest among rivaroxaban users. In conclusion, our meta-analysis suggested a slightly higher risk of GIB with dabigatran use compared with warfarin, whereas no significant difference was found between rivaroxaban and warfarin for GIB risk.

Keywords: dabigatran; gastrointestinal bleeding; real-life; rivaroxaban.

© 2016 The British Pharmacological Society.

Figures

Figure 1

Preferred Reporting Items for Systematic reviews and Meta‐Analyses (PRISMA) flowchart summarizing study identification and selection. GIB, gastrointestinal bleeding; NOAC, non‐vitamin K antagonist oral anticoagulant

Figure 2

Primary analysis of cohort studies: summarized estimates (crude and adjusted) of gastrointestinal bleeding risk among users of non‐vitamin K antagonist oral anticoagulants vs. warfarin. CI; confidence interval; IV, intravenous; NOAC, non‐vitamin K antagonist oral anticoagulant; SE, standard error

Figure 3

Summarized estimates of incidence rate of GIB in NOAC users. CI, confidence interval; GIB, gastrointestinal bleeding; IR, incidence rate per 100 patient‐years; LCL, 95% lower confidence limit; UCL, 95% upper confidence limit

Figure 4

Subgroup analysis: summarized estimates of GIB risk by different dabigatran doses. CI, confidence interval; IV, intravenous; SE, standard error