Tamoxifen-Direct Oral Anticoagulant Combination Did Not Increase Hemorrhage Risk for Patients With Breast Cancer

The addition of tamoxifen to a direct oral anticoagulant was not found to significantly increase the risk of hemorrhage in patients with breast cancer, compared to an aromatase inhibitor plus direct oral anticoagulant.

“Tamoxifen is commonly used as adjuvant therapy in breast cancer and is proposed to interfere with cytochrome P450 enzyme and P-glycoprotein pathways," wrote Tzu-Fei Wang, MD, University of Ottawa at the Ottawa Hospital, Ontario, Canada, and colleagues, adding, “Concurrent use with direct oral anticoagulants poses the threat of a potentially dangerous drug-drug interaction by leading to an increase in hemorrhage risk.”

This population-based, retrospective cohort study included a total of 4753 patients with breast cancer who were prescribed a direct oral anticoagulant (rivaroxaban = 53.2%, apixaban = 35.0%, dabigatran = 10.6%, edoxaban = 1.2%) and either tamoxifen (n = 1179) or an aromatase inhibitor (n = 3574; letrozole = 52.2%, anastrozole = 44.2%, exemestane = 3.6%). The primary outcome was major hemorrhage that required either an emergency department visit or hospitalization following prescription.

In a median follow-up 166 days, there was no association found between tamoxifen plus direct oral anticoagulants and a higher risk of major hemorrhage compared to concurrent treatment with an aromatase inhibitor. In the tamoxifen group, 2.5% of patients experienced a major hemorrhage (23.4 per 1000 person-years) vs 3.3% in the aromatase inhibitor group (31.1 per 1000 person-years) weighted hazard ratio [HR] 0.68; 95% CI, 0.44 to 1.06). These results were similar when adjusting for a more liberal definition of hemorrhage which included any bleeding events or any receipt of blood transfusion.

Patients taking aromatase inhibitors exhibited higher Charlson Comorbidity Index (mean [SD], 1.8 [2.4]) vs those taking tamoxifen (1.5 [2.2]). Patients with more advanced cancer stages (stages III and IV, 569 [15.9%]) were more likely to take aromatase inhibitors than tamoxifen (127 [10.8%]).

Dr Wang and colleagues concluded, “These findings suggest that among [direct oral anticoagulants] users, the concurrent use of tamoxifen is not associated with a higher risk of hemorrhage compared with concurrent use of aromatase inhibitors,” and that these results “should directly inform prescribers regarding the apparent safety of concurrent [direct oral anticoagulants] and tamoxifen use.”

Source:                                        

Wang TF, Clarke AE, Awan AA, et al. Hemorrhage risk among patients with breast cancer receiving concurrent direct oral anticoagulants with tamoxifen vs aromatase inhibitors. JAMA Netw. 2022;5(6):e2219128. doi:10.1001/jamanetworkopen.2022.19128