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No increased hemorrhage risk with concurrent tamoxifen, oral anticoagulants

Author: Laura Cowen

medwireNews: Concurrent use of tamoxifen with a direct oral anticoagulant (DOAC) is not associated with an increased risk for major hemorrhage compared with concurrent use of aromatase inhibitors (AIs) in people with breast cancer, research suggests.

Tzu-Fei Wang (The Ottawa Hospital, Ontario, Canada) and colleagues say their findings “should directly inform prescribers regarding the apparent safety of concurrent DOAC and tamoxifen use.”

They explain that two of the pathways that tamoxifen inhibits – CYP3A4 and P-glycoprotein – are the same pathways that metabolize DOACs, which “poses the threat of a potentially dangerous drug-drug interaction by leading to an increase in hemorrhage risk.”

However, there is limited clinical evidence for this proposed interaction in people with breast cancer.

To address this, Wang and team analyzed the rate of major hemorrhage requiring an emergency department visit or hospitalization among 4753 patients (mean age 77.4 years, 98.4% women) who were prescribed tamoxifen (24.8%) or an AI (75.2%) while also receiving a DOAC between 2009 and 2020. The most commonly prescribed AI was letrozole (52.2%) followed by anastrozole (44.2%), and exemestane (3.6%), and the most used DOACs were rivaroxaban (53.2%) and apixaban (35.0%).

During a median 166 days of follow-up, 2.5% of participants in the tamoxifen group and 3.3% of those in the AI group experienced a major hemorrhage, a nonsignificant difference.

The results were similar when the researchers used a more liberal definition of hemorrhage that included any bleeding event or receipt of a blood transfusion associated with an emergency department visit or hospitalization, with 4.9% and 4.6% in the tamoxifen and AI groups, respectively, experiencing a bleeding event during follow-up.

There was also no association between tamoxifen use and an increased risk for hemorrhage in analyses that accounted for kidney function, limited follow-up to 90 days, stratified participants by incident and prevalent DOAC use, and accounted for cancer duration and the competing risk for death.

And a comparable proportion of tamoxifen and AI users experienced cholecystitis, diverticulitis, or appendicitis (0.8 vs 0.9%).

Writing in JAMA Network Open, Wang et al conclude: “These findings suggest that concerns of a higher risk of clinically relevant hemorrhage with coadministration of tamoxifen and a DOAC for patients with breast cancer are unwarranted and should not influence DOAC use when indicated.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Netw Open 2022; 5: e2219128

Image Credits: © Snezhana Kudryavtseva / Getty Images / iStock

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