Warfarin Is Associated With Higher Rates of Upper But Not Lower Gastrointestinal Bleeding Compared with Direct Oral Anticoagulants: A Population-Based Propensity-Weighted Cohort Study.

BACKGROUND AND AIMS: While overall gastrointestinal bleeding (GIB) rates have been extensively compared between warfarin and direct oral anticoagulants (DOACs), it is still unclear whether upper and lower GIB rates differ between these types of drugs. This study aimed to compare upper and lower GIB rates between warfarin and DOACs in a nationwide cohort. METHODS: Data on all patients in Iceland who received a prescription for oral anticoagulation from 2014 to 2019 were collected and their personal identification numbers linked to the electronic medical record system of the National University Hospital of Iceland and the 4 regional hospitals in Iceland. Inverse probability weighting was used to yield balanced study groups and rates of overall, major, upper, and lower GIB were compared using Cox regression. All GIB events were manually confirmed by chart review. RESULTS: Warfarin was associated with higher rates of upper GIB (1.7 events per 100 person-years vs 0.8 events per 100 person-years; hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.26-3.59) but similar rates of lower GIB compared with DOACs. Specifically, warfarin was associated with higher rates of upper GIB compared with apixaban (HR, 2.63; 95% CI, 1.35-5.13), dabigatran (5.47; 95% CI, 1.87-16.05), and rivaroxaban (HR, 1.74; 95% CI, 1.00-3.05). Warfarin was associated with higher rates of major GIB compared with apixaban (2.3 events per 100 person-years vs 1.5 events per 100 person-years; HR, 1.79; 95% CI, 1.06-3.05), but otherwise overall and major GIB rates were similar in warfarin and DOAC users. CONCLUSIONS: Warfarin was associated with higher rates of upper but not overall or lower GIB compared with DOACs. Warfarin was associated with higher rates of major GIB compared with apixaban.