Comparing the risk of gastrointestinal bleeding associated with direct oral anticoagulants

July 17, 2017

Gastrointestinal (GI) bleeding is a significant source of morbidity among patients initiating anticoagulation. Performing a risk-benefit analysis is especially important for elderly patients, because when these patients experience GI bleeding, they typically have a poor prognosis and experience a significant impact on their quality of life. As direct oral anticoagulants (DOACs) become more commonly prescribed for patients with atrial fibrillation, assessing the risk of GI bleeding associated with these medications becomes more critical.

In a recent study published in Gastroenterology, Mayo researchers investigated three DOACs commonly prescribed for the treatment of nonvalvular atrial fibrillation — dabigatran, rivaroxaban and apixaban — to determine which has the more favorable GI safety profile. In addition, they compared differences in age-related risk of bleeding associated with these drugs.


Mayo researchers conducted a retrospective, propensity-matched study using administrative claims data from the OptumLabs data warehouse of privately insured individuals and Medicare Advantage enrollees. Patients with nonvalvular atrial fibrillation and incident exposure to dabigatran, rivaroxaban or apixaban, from Oct. 1, 2010, to Feb. 28, 2015, were grouped into three propensity-matched cohorts.

Researchers compared data for rivaroxaban vs. dabigatran in 31,574 patients; data for apixaban vs. dabigatran in 13,084 patients; and data for apixaban vs. rivaroxaban in 13,130 patients. Using Cox proportional hazards models, stratified by age, the researchers estimated rates of total GI bleeding. Mayo researchers also calculated the number needed to harm (NNH) for each drug with regard to GI bleeding.

"Gastrointestinal bleeding is a significant source of drug complications among patients taking anticoagulation and is one of the key issues to consider when assessing the risk-benefit trade-offs," says Neena S. Abraham, M.D., a gastroenterologist, health sciences researcher and center site director of the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery at Mayo Clinic's campus in Arizona. "Our results provide clinicians with a way to directly compare these newer medications," says Dr. Abraham, the study's lead author.

Key findings

  • Apixaban had the most favorable GI safety profile compared with both dabigatran and rivaroxaban across all three age groups. Rivaroxaban had the least favorable GI safety profile.
  • Patients using apixaban were 61 percent less likely to experience GI bleeding than those on dabigatran (hazard ratio [HR], 0.39; 95 percent confidence interval [CI], 0.27-0.58).
  • Patients using dabigatran were 20 percent less likely to experience bleeding than those on rivaroxaban (HR, 1.20; 95 percent CI, 1.00-1.45).
  • GI bleeding events among patients taking DOAC agents increased with age, with the greatest risk occurring in individuals age 75 and older. Apixaban appears to be the safest of the three drugs studied in this age group.

"We found that apixaban may be the preferred agent among DOACs when GI bleeding is an important consideration in guiding treatment decisions," says Dr. Abraham. "This is true across all age groups, but is especially important among those over the age of 75, where the risk of GI bleeding is generally much greater."

Dr. Abraham notes that the Mayo study didn't include a fourth Food and Drug Administration-approved DOAC, edoxaban, because there were not enough patients using it to compare with the other medications.

For more information

Abraham NS, et al. Gastrointestinal safety of direct oral anticoagulants: A large population-based study. Gastroenterology. 2017;152:1014.