Bleeding risk in patients receiving concurrent treatment with direct oral anticoagulants and corticosteroids: A systematic review

Background: Direct oral anticoagulants (DOACs) and corticosteroids are frequently co-prescribed in clinical practice. While both drug classes independently increase bleeding risk, the impact of their concurrent use remains unclear. Aim: To systematically review the literature on bleeding outcomes associated with combined DOAC and corticosteroid use. Methods: We conducted a systematic review following PRISMA guidelines. PubMed, Web of Science, and Scopus were searched for studies reporting bleeding in patients receiving both DOACs and corticosteroids. Cumulative incidences of any bleeding and major bleeding (MB) were estimated using a random-effects model, and study quality assessed using the Newcastle-Ottawa Scale and the Cochrane RoB2. Subgroup analyses were performed for patients treated for atrial fibrillation (AF) and venous thromboembolism (VTE). Results: Nine studies including 87,209 patients were included. The weighted cumulative incidence of any bleeding was 7.0% (95% CI 3.96-12.01%), and of MB 6.6% (95% CI 6.21-6.97%). Heterogeneity was high for any bleeding in the overall and in the AF populations, likely reflecting differences in patient characteristics, corticosteroid exposure, follow-up duration, and study design, whereas heterogeneity was minimal in the VTE subgroup. Variability in bleeding definitions, limited reporting of corticosteroid dose and duration, and absence of stratification by DOAC type/dose or bleeding site further contributed to differences in observed incidences. Conclusions: Available evidence suggests a clinically relevant incidence of bleeding among patients receiving concomitant DOAC and corticosteroid therapy. Clinicians should carefully evaluate the risk-benefit profile, monitor patients closely, and consider preventive strategies. Future studies are needed to improve risk characterization in this common clinical scenario.