Oral Anticoagulants and Risk of Bleeding and Death in Cancer-Associated Venous Thromboembolism

Background: Among patients with cancer-associated VTE (Ca-VTE), anticoagulant choice may impact outcomes such as hospitalized bleeding and death, with potential differences across different cancer sites. Objectives: This study aimed to evaluate the risks of hospitalized bleeding and death by oral anticoagulant (OAC) prescribed (ie, apixaban, rivaroxaban, and warfarin), overall and by cancer site. Methods: Patients with Ca-VTE aged ≥65 years were identified from the U.S. Medicare 20% sample databases for years 2011 to 2019. Algorithms based on International Classification of Diseases codes were used to define venous thromboembolism, cancer site, comorbidities, and hospitalized bleeding. Cox regression was used, with follow-up restricted to 6 months. Results: Among the 30,342 patients with Ca-VTE who filled prescriptions for OACs (apixaban: 6,546; rivaroxaban: 7,936; warfarin: 15,860), 634 experienced incident hospitalized bleeding and 5,977 died within 6 months of incident venous thromboembolism. Overall, the hospitalized bleeding HR (95% CI) for apixaban vs rivaroxaban was 0.68 (0.56-0.83). This pattern was present for most cancer sites (ie, breast, colon, lung, and prostate), though precision was poor and associations were not statistically significant. No clear pattern emerged when comparing apixaban or rivaroxaban to warfarin. For mortality there was no association overall (HR apixaban vs rivaroxaban: 0.99 [0.91-1.08]). Results were generally similar in analyses stratified by age category, sex, prevalent kidney disease status, and metastatic cancer status. Conclusions: Among patients with Ca-VTE, apixaban may be associated with lower risk of hospitalized bleeding than rivaroxaban. Additional research is needed to understand associations of OAC prescribed with all-cause mortality among patients with Ca-VTE.