Increased Upper GI Bleeding With Warfarin vs Direct Oral Anticoagulants

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Researchers compared the rates of lower vs upper gastrointestinal bleeding resulting from warfarin vs direct oral anticoagulants.

Warfarin is associated with higher rates of upper gastrointestinal bleeding (GIB) compared with all direct oral anticoagulants (DOACs), and with major bleeding compared with apixaban, in particular, according to study results published in Clinical Gastroenterology and Hepatology.

Researchers conducted a nationwide study in Iceland using data from 2014 to 2019 on patients (N=7081) prescribed oral anticoagulants (warfarin and DOACs). Study groups (apixaban, n=2098; dabigatran, n=474; rivaroxaban, n=3106; warfarin, n=1403) were assigned using inverse probability weighting, and Cox regression was used to compare rates of upper, lower, overall, and major GIB. Chart review was performed to manually confirm all GIB events.

Primary outcomes included upper, lower, or overall GIB that was clinically relevant, defined as GIB leading to medical intervention, unscheduled physician contact, or temporary discontinuation of treatment.

Rates of upper GIB were higher in patients who received warfarin vs apixaban (hazard ratio [HR], 2.63; 95% CI, 1.35-5.13), rivaroxaban (HR, 1.74; 95% CI, 1.00-3.05), and dabigatran (HR, 5.47; 95% CI, 1.87-16.05). Although the rates of overall and major GIB were similar between warfarin and DOACs, warfarin was associated with a comparatively higher rate of upper GIB (HR, 2.12; 95% CI, 1.26-3.59; 1.7 events/100 person-years [py] vs 0.8 events/100 py). Warfarin was also associated with higher rates of major GIB vs apixaban (HR, 1.79; 95% CI, 1.06-3.05; 2.3 events/100 py vs 1.5 events/100 py).

Study limitations include potential residual confounding, a lack of data on over-the-counter medications and baseline laboratory results, and the use of International Society on Thrombosis and Hemostasis criteria to define major GIB.

The study researchers concluded that “DOACs may be preferable to warfarin in patients at high risk [for] upper GIB,” particularly for those with a history of peptic ulcer disease or major upper GIB.


Ingason AB, Hreinsson JP, Agustsson AS, et al. Warfarin is associated with higher rates of upper but not lower gastrointestinal bleeding compared to direct oral anticoagulants: a population-based propensity-weighted cohort study. Clin Gastroenterol Hepatol. Published online August 13, 2022. doi:10.1016/j.cgh.2022.06.033