Nationwide Trends in Gastrointestinal Bleeding Mortality Before and After the Widespread Adoption of Direct Oral Anticoagulants in the United States, 2007-2020.

backgroundGastrointestinal (GI) bleeding remains a significant risk for patients on long-term anticoagulation. While direct oral anticoagulants (DOACs) have replaced warfarin due to easier dosing and monitoring, their overall impact on GI bleeding mortality in the U.S. is still uncertain.

methodsWe conducted a nationwide interrupted time-series analysis using CDC WONDER mortality data (2007-2020) and Medicare Part D prescription data (2010-2020). GI bleeding deaths were identified using ICD-10 codes. Age-adjusted and exposure-adjusted mortality rates were calculated per 100,000 population and per 100,000 DOAC users, respectively. Segmented regression assessed trends before and after widespread DOAC use, with 2014 as the intervention year.

resultsFrom 2007 to 2020, age-adjusted GI bleeding mortality increased from 0.6 to 1.3 deaths per 100,000 population. Over the same period, DOAC prescriptions rose from 3 to 72% of all oral anticoagulant prescriptions, surpassing warfarin by 2015-2016. Exposure-adjusted GI bleeding mortality declined from 29.5 to 20.0 deaths per 100,000 DOAC users, reflecting a 32% relative reduction (p = 0.014 after excluding 2020). Interrupted time-series regression showed a significant pre-DOAC upward slope but no post-2014 increase, indicating stability in age-adjusted mortality despite expanding anticoagulant exposure.

conclusionAt the population level, GI bleeding mortality rose modestly during the DOAC era, reflecting expanded anticoagulant use and an aging demographic. Importantly, the individual risk of fatal GI bleeding decreased, indicating improved safety and management for patients on anticoagulation. These results underscore the enhanced national safety profile of DOACs compared to warfarin, supporting their continued use in clinical practice.