Benefit and risk of oral anticoagulant initiation strategies in patients with atrial fibrillation and cancer: a target trial emulation using the SEER-Medicare database

Oral anticoagulants (OACs) are recommended for patients with atrial fibrillation (AFib) having CHA2DS2-VASc score >= 2. However, the benefits of OAC initiation in patients with AFib and cancer at different levels of CHA2DS2-VASc is unknown. We included patients with new AFib diagnosis and a record of cancer (breast, prostate, or lung) from the 2012-2019 Surveillance, Epidemiology, and End Results (SEER)-Medicare database (n = 39,915). Risks of stroke and bleeding were compared between 5 treatment strategies: (1) initiated OAC when CHA2DS2-VASc >= 1 (n = 6008), (2) CHA2DS2-VASc >= 2 (n = 8694), (3) CHA2DS2-VASc >= 4 (n = 20,286), (4) CHA2DS2-VASc >= 6 (n = 30,944), and (5) never initiated OAC (reference group, n = 33,907). Confounders were adjusted using inverse probability weighting through cloning-censoring-weighting approach. Weighted pooled logistic regressions were used to estimate treatment effect [hazard ratios (HRs) and 95% confidence interval (95% CIs)]. We found that only patients who initiated OACs at CHA2DS2-VASc >= 6 had lower risk of stroke compared without OAC initiation (HR 0.64, 95% CI 0.54-0.75). All 4 active treatment strategies had reduced risk of bleeding compared to non-initiators, with OAC initiation at CHA2DS2-VASc >= 6 being the most beneficial strategy (HR = 0.49, 95% CI 0.44-0.55). In patients with lung cancer or regional/metastatic cancer, OAC initiation at any CHA2DS2-VASc level increased risk of stroke and did not reduce risk of bleeding (except for Regimen 4). In conclusion, among cancer patients with new AFib diagnosis, OAC initiation at higher risk of stroke (CHA2DS2-VASc score >= 6) is more beneficial in preventing ischemic stroke and bleeding. Patients with advanced cancer or low life-expectancy may initiate OACs when CHA2DS2-VASc score >= 6.