Gastrointestinal bleeding (GIB) is a critical complication in patients receiving antithrombotic agents (ATs). We aimed to (1) investigate the incidence and timing of major GIB, (2) classify the etiologies of upper GIB (UGIB) and lower GIB (LGIB), and (3) identify the risk factors for GIB following AT initiation during long-term follow-up. 

A retrospective cohort study of 8,699 patients with atrial fibrillation (AFib) initiating ATs was conducted using electronic health records from a tertiary hospital. Major GIB was defined as bleeding requiring therapeutic intervention and classified anatomically as UGIB or LGIB. Incidence rates were calculated, and risk factors were examined via multivariable Cox regression and 1-year landmark analysis.

: During a mean follow-up of 6.5 years, 2.4% of patients experienced major GIB (1.7% UGIB; 0.8% LGIB), and incidence was the highest in the first year (79.0 per 10,000 person-years). Ulcers and angiodysplasia were the leading etiologies. In addition to well-known comorbidities, low baseline hemoglobin and albumin were independently associated with the increased GIB risk. As hemoglobin decreased, the risk increased progressively, beginning at ≤12 g/dL and peaking at ≤8 g/dL (adjusted HR 10.95, 95% CI 6.36–18.85). Landmark analysis confirmed that low hemoglobin predicted GIB in the first year and thereafter.

: Major GIB is the most frequent in the first year following AT initiation but remains a long-term concern. Low baseline hemoglobin and albumin levels, as readily available markers, may be valuable in the early identification and risk stratification of high-risk patients with AFib.