Benefit and Risk of Oral Anticoagulant Initiation Strategies in Patients With Atrial Fibrillation and Cancer: A Target Trial Emulation Using the SEER-Medicare Database

OBJECTIVES: Oral anticoagulants (OACs) are recommended for patients with atrial fibrillation (AFib) having a CHA₂DS₂-VASc score ≥2. However, the benefits of OAC initiation at different levels of CHA₂DS₂-VASc in patients with AFib and cancer are unknown.

METHODS: We conducted a retrospective cohort study by emulating a hypothetical target trial using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We included cancer patients (breast, prostate, or lung), newly diagnosed with AFib between 2012 and 2019, with 12-month continuous enrollment before AFib diagnosis (n=39915), and excluded those with other indications for OACs, prior OAC use, recent stroke, major surgery, critical bleeding or severe renal diseases. We compared risks of stroke and bleeding were compared between five treatment strategies: (1) initiating OAC when CHA₂DS₂-VASc ≥1 (n=6008), (2) CHA₂DS₂-VASc ≥2 (n=8694), (3) CHA₂DS₂-VASc ≥4 (n=20286), (4) CHA₂DS₂-VASc ≥6 (n=30944), and (5) never initiating OAC (reference group, n=33907). Confounders (demographics, socioeconomic factors, comorbidities, cancer characteristics, and medication history) were adjusted using the cloning-censoring-weighting approach. Inverse probability weighted pooled logistic regressions were used to estimate hazard ratios (HRs) and 95% confidence interval (95% CIs).

RESULTS: Only cancer patients who initiated OACs at CHA₂DS₂-VASc ≥6 had a lower risk of stroke (HR=0.64, 95% CI 0.54-0.75) than never initiators. All four 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 the risk of stroke and did not reduce the risk of bleeding (except for Regimen 4).

CONCLUSIONS: Among cancer patients with newly diagnosed AFib, OAC initiation at higher risk of stroke is more beneficial in preventing ischemic stroke and bleeding. Patients with advanced cancer or low life-expectancy may not need OAC therapy until higher CHADs-VASc scores.

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