GI safety profile varies among direct oral anticoagulants

Three propensity-matched cohorts of patients with nonvalvular atrial fibrillation who had incident exposure to dabigatran, rivaroxaban, or apixaban were compared.


Direct oral anticoagulants vary in their GI safety, a recent study found.

Researchers performed a retrospective study with administrative claims data on patients who were privately insured or enrolled in Medicare Advantage. Three propensity-matched cohorts of patients with nonvalvular atrial fibrillation who had incident exposure to dabigatran, rivaroxaban, or apixaban from Oct. 1, 2010, through Feb. 28, 2015, were compared. Rivaroxaban was compared with dabigatran, apixaban was compared with dabigatran, and apixaban was compared with rivaroxaban. Edoxaban was not included because at the time its market share was very limited and the sample size was small. Rates of total GI bleeding were estimated by Cox proportional hazards models stratified by age. Study results were published online Dec. 31 by Gastroenterology.

Data were compared for rivaroxaban versus dabigatran in 31,574 patients, data on apixaban versus dabigatran were compared for 13,084 patients, and data on apixaban versus rivaroxaban were compared for 13,130 patients. The mean age range for all the cohorts was 69.2 years to 72.2 years. Across all cohorts, the mean CHA2DS2-VASC score was between 3.2 and 4.0, and the mean HAS-BLED score was between 2.2 and 2.4. GI bleeding was more common in patients taking rivaroxaban than in those taking dabigatran (hazard ratio, 1.20; 95% CI, 1.00 to 1.45). Overall incidence rate for GI bleeding events was 2.74 per 100 patient-years for rivaroxaban and 2.02 per 100 patient-years for dabigatran.

A lower risk for GI bleeding was associated with apixaban versus dabigatran (hazard ratio, 0.39; 95% CI, 0.27 to 0.58), with an overall incidence rate of 1.38 per 100 patient-years versus 2.73 per 100 patient-years. The same was true for apixaban versus rivaroxaban (hazard ratio, 0.33; 95% C, 0.22 to 0.49), with an overall incidence rate of 1.34 per 100 person-years versus 3.54 per 100 patient-years (P<0.001 for both apixaban comparisons). GI bleeding rates increased with all of the direct oral anticoagulants in patients 75 years of age or older, with apixaban associated with the fewest GI bleeds. In these very elderly patients, apixaban was less likely than dabigatran or rivaroxaban to be associated with GI bleeding (hazard ratios, 0.45 [95% CI, 0.29 to 0.71] and 0.39 [95% CI, 0.25 to 0.61], respectively). Median time to GI bleeding was longer for dabigatran than for apixaban and rivaroxaban (<120 days vs. <90 days, respectively).

The authors cautioned that their study was observational and that unmeasured residual confounding cannot be completely excluded. In addition, they noted that duration of follow-up for the three drugs differed due to different FDA approval dates and that they could not assess the effects of other medications, such as over-the-counter aspirin, NSAIDs, or proton-pump inhibitors, among other limitations. However, they concluded that of the three direct oral anticoagulants assessed in their study, apixaban was associated with the lowest risk for GI bleeding across all age groups. “Confirmation of our results by other investigators will help guide clinical decision-making when individualizing treatment preferences based on patient indication, age and preference for anticoagulation,” the authors wrote.