Gastrointestinal Surgery Status and the Risks of Ischemic Stroke and Safety Outcomes With Direct Oral Anticoagulants Versus Warfarin in Atrial Fibrillation: A Nationwide Population-Based Cohort Study

Background and Purpose: Although gastrointestinal (GI) surgery can affect drug efficacy, its impact on oral anticoagulants (OACs) remains unclear. This study investigated the impact of GI surgery on the comparative effectiveness and safety of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation (AF). Methods: Using a nationwide South Korean claims database, AF patients prescribed OACs between 2015 and 2021 were analyzed. The primary outcome was ischemic stroke, and secondary outcomes were major bleeding, all-cause death, and composite outcome (ischemic stroke, major bleeding, all-cause death). Outcomes were compared by OAC type (DOAC vs. warfarin) and GI surgery status using inverse probability of treatment weighting and a Fine-Gray subdistribution hazard model with time-varying covariates. Results: Among 388,214 AF patients (mean age, 71.9 yr; 42.7% male), 6,907 (1.8%) underwent GI surgery. The effect of GI surgery differed between warfarin and DOACs for ischemic stroke (Pint= 0.018), with increased risk for warfarin (adjusted HR [aHR]: 2.32; 95% confidence interval [CI] 1.17-4.62), but not for DOACs (aHR: 0.97 [95% CI 0.77-1.22]) after surgery. Effects of surgery on major bleeding, all-cause death, and composite outcome did not differ. In post-GI surgery setting, DOACs demonstrated lower ischemic stroke risk (aHR: 0.35 [95% CI 0.17-0.72]) and comparable risks for other outcomes. Exploratory analyses by surgery location suggested a more favorable profile of DOACs after upper GI surgery. Conclusions: In AF patients, GI surgery significantly increased ischemic stroke risk among warfarin users, but not among DOAC users. DOACs showed generally favorable profiles after GI surgery and may remain a reasonable anticoagulant, with potentially more favorable profile after upper GI surgery.