Direct Oral Anticoagulants Increase Overall but Not Major Bleeding in Critically Ill Chronic Kidney Disease Patients With Pulmonary Embolism

Background Patients with pulmonary embolism (PE) and chronic kidney disease (CKD) have a fragile hemostatic balance, yet evidence comparing bleeding risk between direct oral anticoagulants (DOACs) and warfarin in critically ill patients remains limited. We compared overall and major bleeding risks associated with DOACs versus warfarin in ICU patients with PE and CKD. Methods We conducted a retrospective cohort study using the MIMIC-IV (v3.1) database. Adult ICU patients with PE and an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 treated with DOACs or warfarin were included. Propensity score matching (PSM) was used as the primary adjustment strategy, with stabilized inverse probability of treatment weighting (IPTW) as sensitivity analysis. Cox proportional hazards models were applied. The primary outcome was any bleeding, and the secondary outcome was major bleeding. Results Among 1,363 patients, 832 received warfarin and 531 received DOACs. After PSM, 1,038 patients were well balanced. In IPTW-weighted analyses, DOAC use was associated with a higher risk of any bleeding compared with warfarin (HR 1.37, 95% CI 1.13–1.66; P = 0.001), while no significant difference was observed for major bleeding (HR 0.97, 95% CI 0.74–1.28; P = 0.84). Results were consistent in the PSM cohort. Renal function did not significantly modify the relative bleeding risk. Conclusions In critically ill patients with PE and CKD, DOACs were associated with increased overall bleeding but not major bleeding compared with warfarin. Differentiating non-major from major bleeding is essential when selecting anticoagulant therapy in this population.