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

Background 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 are inconclusive.Methods We conducted a retrospective cohort study by emulating a target trial. Patients with a record of cancer (breast, prostate, or lung), newly diagnosed with AFib initiated DOACs or warfarin within 3 months after AFib diagnosis from the 2012-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare database were included. We compared the risk of ischemic stroke, major bleeding, and secondary outcomes (venous thromboembolism, intracranial bleeding, gastrointestinal bleeding, and non-critical site bleeding) between patients who initiated DOACs and warfarin. 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 were used to estimate treatment effect with hazard ratios (HRs) with 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 adjusted intention-to-treat analysis, patients initiated DOACs had no statistically significant difference in risk of 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 adjusted per-protocol analysis, there was no statistical difference in risk of ischemic stroke (HR = 1.81, 95% CI 0.75-4.36) and lower risk for major bleeding, but the 95% CI was wide (HR = 0.35, 95% CI 0.12-0.99) among DOAC initiators compared to warfarin initiators. The benefits in secondary outcomes were in favor of DOACs. The findings remained consistent across subgroups and sensitivity analyses.Conclusion DOACs are safe and effective alternatives to warfarin in the management of patients with AFib and cancer.