Risks of thrombosis and hemorrhage in concurrent use of anticoagulants and potential interacting prostate cancer agents

BACKGROUND: Pharmacokinetic studies suggest that specific prostate cancer therapies may alter the metabolism of direct oral anticoagulants (DOACs), leading to elevated risks of thrombosis or bleeding. METHODS: To assess the risk of thrombosis or bleeding, population-based, retrospective, parallel analyses were conducted in Ontario and Alberta, Canada, among adults patients with prostate cancer who were prescribed a DOAC and a potentially interacting androgen receptor pathway inhibitor (including enzalutamide, apalutamide, or abiraterone) compared with non-DOACs between 2012 and 2023. Analyses were stratified based on a DOAC-inducer cohort (enzalutamide or apalutamide, which might increase the risk of thrombosis) and a DOAC-inhibitor cohort (abiraterone, which might increase the risk of bleeding). Overlap weighted Cox proportional hazard models accounting for 37 covariates were performed independently in each jurisdiction and were pooled using random-effects meta-analysis. RESULTS: In total, 2997 individuals were included (2107 from Ontario and 890 from Alberta). In patients who received enzalutamide or apalutamide, there was no increased risk of all thrombosis in the DOAC groups compared with the non-DOAC groups (pooled hazard ratio, 0.83; 95% confidence interval, 0.36-1.93). In patients who received abiraterone, no significant differences were observed in any bleeding events comparing the DOAC and non-DOAC groups (pooled hazard ratio, 1.16; 95% confidence interval, 0.10-13.99). The results were consistent in multiple sensitivity analyses. CONCLUSIONS: The concurrent use of enzalutamide, apalutamide, or abiraterone with DOACs did not contribute to clinically meaningful changes in the risk of thrombosis or bleeding in individuals with prostate cancer.