GI bleeding risks with warfarin and DOACs compared

Warfarin was associated with more upper GI bleeding than direct oral anticoagulants (DOACs), a but similar risk of lower GI bleeding, a study found.

The study was based on data from all patients in Iceland who received a prescription for oral anticoagulation from 2014 to 2019. Inverse probability weighting was used to yield balanced study groups, and rates of overall, major, upper, and lower GI bleeding were compared using Cox regression. Results were published by Clinical Gastroenterology and Hepatology on Aug. 13.

Warfarin was associated with more than twice the rate of upper GI bleeding compared to DOACs (1.7 vs. 0.8 events per 100 person-years; hazard ratio [HR], 2.12 [95% CI, 1.26 to 3.59]) but a similar rate of lower GI bleeding. When specific DOACs were examined, the risk of an upper GI bleed was significantly increased with warfarin compared to apixaban (HR, 2.63; 95% CI, 1.35 to 5.13), dabigatran (HR, 5.47; 95% CI, 1.87 to 16.05), and rivaroxaban (HR, 1.74; 95% CI, 1.00 to 3.05). Warfarin was associated with higher risk of major GI bleeding only versus apixaban (2.3 vs. 1.5 events per 100 person-years; HR, 1.79 [95% CI, 1.06 to 3.05]).

The study authors noted that the finding of higher risk of upper GI bleeding with warfarin than DOACs was consistent with previous randomized controlled trials but differed from population-based studies, probably because it was difficult for those studies to differentiate between upper and lower GI bleeding. “As the drugs spend proportionally much longer time in the lower than the upper GI tract, it is perhaps unsurprising that DOACs are proportionally more likely to cause” lower GI bleeding, the authors said.

The results suggest that DOACs may be preferable to warfarin in patients at high risk of upper GI bleeding, such as those with a history of such bleeds or peptic ulcer disease, the authors said. They noted several limitations to the study, including the risk of residual confounding and lack of data on baseline laboratory results and over-the-counter medication use.