Direct oral anticoagulants in the prevention of stroke in breast cancer patients with atrial fibrillation during adjuvant endocrine therapy: A cohort study

Background: Atrial fibrillation (AF) is a frequent comorbidity in malignant patients. Anticancer therapies complicate anticoagulant strategy. We evaluated the safety and efficacy of long-term use of direct oral anticoagulants (DOACs) in breast cancer women.

Methods: In a prospective cohort study we enrolled 48 consecutive radically treated breast cancer women with AF (median age 63 [interquartile range 56-69] years, CHA₂DS₂-VASc 2 (Huikuri et al., 2018; Neal et al., 2015 [2,3]) score) and adjuvant hormonal therapy. Thromboembolic complications (stroke, transient ischemic attack [TIA], venous thromboembolism [VTE]) and bleeding events (major and clinically relevant non-major bleeding [CRNMB]) were recorded in follow-up.

Results: During a median follow-up of 40 (interquartile range 28-50.5) months 13 (27%) patients received apixaban, 22 (46%) rivaroxaban, and 13 (27%) dabigatran. One stroke (2.3%/year) and two CRNMBs (4.6%/year) were observed on apixaban. One TIA (1.3%/year), three major bleedings and two CRNMBs (6.7%/year, combined) were reported on rivaroxaban. Three VTE were documented in dabigatran treated individuals (7.8%/year), without any bleeding or cerebrovascular events. Women with thromboembolic events had higher body mass index (32 (Pathak et al., 2014; Watanabe et al., 2008; Flack et al., 2017; Kochar et al., 2018; Raskob et al., 2018 [29-33]) vs. 26 (Kaatz et al., 2015; Ruff et al., 2014; Chen et al., n.d.; Panchal et al., n.d.; Zhu et al., 2016; Pathak et al., 2014 [24-29]) kg/m², p = 0.02) and CHA₂DS₂-VASc score (3 (Neal et al., 2015 [3]) vs. 2 (Björck et al., 2013; Huikuri et al., 2018; Neal et al., 2015 [1-3]), p = 0.02). Most thromboembolic complications (n = 4, 80%) and all three major bleedings were observed in tamoxifen users, while three of four CRNMBs occurred on aromatase inhibitors. Mortality rates were low (apixaban, n = 1 [2.3%/year], rivaroxaban, n = 3 [5.22%/ year], and dabigatran, n = 2 [4%/ year]). No death was related to bleeding.

Conclusions: This study suggests that DOACs are an effective and safe therapeutic option in breast cancer patients with AF during adjuvant hormonal therapy.

Keywords: Anticoagulants; Atrial fibrillation; Bleeding risk; Breast cancer; Ischemic risk.