Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation and Cancer: A Target Trial Emulation From SEER-Medicare Database

OBJECTIVES: Direct oral anticoagulants (DOACs) are preferred over warfarin in patients with atrial fibrillation (AFib). However, their safety and effectiveness in patients with AFib and cancer remain unclear.

METHODS: We conducted a retrospective cohort study by emulating a target trial, including cancer patients (breast, prostate, or lung) initiating DOACs or warfarin within 3 months after new AFib diagnosis from the 2012-2019 Surveillance, Epidemiology, and End Results - Medicare database. We compared the risk of developing ischemic stroke, major bleeding, and secondary outcomes (venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, and non-critical site bleeding) between patients who initiated DOACs versus warfarin. Patients were followed from DOACs/warfarin initiation (index date) until outcome occurrence, death, end of continuous enrollment, or 12 months after the index date, whichever came first. Inverse probability treatment weights and inverse probability censoring weights were used to adjust imbalanced patient and disease characteristics and loss to follow-up between the two groups. Weighted pooled logistic regression was used to estimate the hazard ratios (HRs) and 95% confidence interval (95% CIs).

RESULTS: The incidence rates of stroke and major bleeding between DOAC and warfarin initiators were 9.97 vs. 9.91 and 7.74 vs 9.24 cases per 1000 person-years, respectively. In the intention-to-treat analysis, patients on DOACs had a similar risk for ischemic stroke (HR=0.87, 95% CI 0.52-1.44) and major bleeding (HR=1.14, 95% CI 0.77-1.68) compared to those initiated warfarin. In the per-protocol analysis, DOAC initiators had similar risk for ischemic stroke (HR=1.81, 95% CI 0.75-4.36) and lower risk for major bleeding (HR=0.35, 95% CI 0.12-0.99) compared to warfarin initiators. The risks of developing secondary outcomes were lower for DOACs. The findings were consistent across subgroups and sensitivity analyses.

CONCLUSIONS: DOACs appear to be a safe and effective alternative to warfarin in patients with Afib and cancer, with a potential lower risk of bleeding.

See COI here.