Hemoglobin Decline After Oral Anticoagulation Initiation and Subsequent Cancer Detection in Patients With Atrial Fibrillation

BACKGROUND: Previous studies evaluating cancer risk during oral anticoagulation (OAC) have focused on overt bleeding events, whereas the significance of hemoglobin (Hb) decline in the absence of clinically overt bleeding events after OAC initiation has not been evaluated. OBJECTIVES: The purpose of this study was to evaluate the association between Hb decline after OAC initiation in the absence of clinically overt bleeding events and subsequent cancer risk in patients with atrial fibrillation (AF). METHODS: Using the Korean National Health Insurance Service database linked to serial health examinations, 6,789 patients with AF were identified who underwent 2 examinations within 1 year before and after OAC initiation. Patients with prior cancer, end-stage renal disease, overt bleeding, or early OAC discontinuation were excluded. Patients were classified by Hb change (Hb decrease ≥2 g/dL vs no significant decrease). The primary outcome was incident cancer; secondary outcomes included site-specific cancers, all-cause mortality, thromboembolic events, and bleeding outcomes. RESULTS: During a median follow-up period of 10.6 months, patients with Hb decreases ≥2 g/dL had a higher incidence of overall cancer than those without (6.7 vs 4.3 per 100 person-years; adjusted HR: 1.42; 95% CI: 1.10-1.97). The association was particularly evident for gastrointestinal cancers (adjusted HR: 1.78; 95% CI: 1.12-2.83). Cancer risk associated with Hb declines was greater in older patients, those with chronic kidney disease, and those receiving antiplatelet therapy (P for interaction < 0.05). Hb decline was also associated with higher all-cause mortality and major bleeding, with no differences in stroke. CONCLUSIONS: In patients with AF initiating OAC, Hb decline ≥2 g/dL in the absence of clinically overt bleeding events is associated with increased cancer risk, particularly gastrointestinal malignancy, and higher mortality.