title: 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.
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong.
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong.|Research Department of Practice and Policy, School of Pharmacy, University College London, London, UK.
authors.forename: Ian C K
authors.initials: IC
authors.lastname: Wong
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong.
authors.forename: Shweta
authors.initials: S
authors.lastname: Anand
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Wai K
authors.initials: WK
authors.lastname: Leung
authors.affiliation: Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors.forename: Chung Wah
authors.initials: CW
authors.lastname: Siu
authors.affiliation: Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong.
authors.forename: Esther W
authors.initials: EW
authors.lastname: Chan
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D000069604:Dabigatran / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000009:adverse effects; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran
keywords: dabigatran; gastrointestinal bleeding; real-life; rivaroxaban