Rivaroxaban Is Associated With Higher Rates of Gastrointestinal Bleeding Than Other Direct Oral Anticoagulants : A Nationwide Propensity Score-Weighted Study

Ann Intern Med. 2021 Nov;174(11):1493-1502. doi: 10.7326/M21-1474. Epub 2021 Oct 12.


Background: Gastrointestinal bleeding (GIB) rates for direct oral anticoagulants (DOACs) and warfarin have been extensively compared. However, population-based studies comparing GIB rates among different DOACs are limited.

Objective: To compare rates of GIB among apixaban, dabigatran, and rivaroxaban.

Design: Nationwide population-based cohort study.

Setting: Landspítali-The National University Hospital of Iceland and the 4 regional hospitals in Iceland.

Patients: New users of apixaban, dabigatran, and rivaroxaban from 2014 to 2019.

Measurements: Rates of GIB were compared using inverse probability weighting, Kaplan-Meier survival estimates, and Cox regression.

Results: In total, 2157 patients receiving apixaban, 494 patients receiving dabigatran, and 3217 patients receiving rivaroxaban were compared. For all patients, rivaroxaban had higher overall rates of GIB (3.2 vs. 2.5 events per 100 person-years; hazard ratio [HR], 1.42 [95% CI, 1.04 to 1.93]) and major GIB (1.9 vs. 1.4 events per 100 person-years; HR, 1.50 [CI, 1.00 to 2.24]) compared with apixaban. Rivaroxaban also had higher GIB rates than dabigatran, with similar point estimates, although the CIs were wider and included the possibility of a null effect. When only patients with atrial fibrillation were included, rivaroxaban was associated with higher rates of overall GIB than apixaban (HR, 1.40 [CI, 1.01 to 1.94]) or dabigatran (HR, 2.04 [CI, 1.17 to 3.55]). Dabigatran was associated with lower rates of upper GIB than rivaroxaban in both analyses.

Limitations: Unmeasured confounding and small subgroup analyses.

Conclusion: Rivaroxaban was associated with higher GIB rates than apixaban and dabigatran regardless of treatment indication.

Primary funding source: Icelandic Centre for Research and Landspítali-The National University Hospital of Iceland.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Dabigatran / adverse effects
  • Digestive System Diseases / complications
  • Digestive System Diseases / epidemiology
  • Factor Xa Inhibitors / adverse effects*
  • Female
  • Follow-Up Studies
  • Gastrointestinal Hemorrhage / chemically induced*
  • Gastrointestinal Hemorrhage / epidemiology
  • Humans
  • Iceland / epidemiology
  • Male
  • Propensity Score
  • Pyrazoles / adverse effects
  • Pyridones / adverse effects
  • Rivaroxaban / adverse effects*
  • Ulcer / complications
  • Ulcer / epidemiology


  • Factor Xa Inhibitors
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban
  • Dabigatran