Addition of malignancy into the CHADS2/CHA2DS2VASc score: better prediction of stroke risk in individuals with cancer and atrial fibrillation

The CHADS₂ and CHA₂DS₂VASc scoring systems guide thromboprophylaxis in atrial fibrillation (AF), but their performance is limited in patients with cancer. This study evaluated whether malignancy functions as an independent risk factor for ischemic stroke among patients with AF. Using the TriNetX research network, we identified patients with AF with and without malignancy between 2015 and 2022, excluding those with prior cerebrovascular disease. Propensity score matching for CHA₂DS₂VASc variables and anticoagulation yielded two cohorts of 234,428 patients each. The primary outcome was ischemic stroke; secondary outcomes included major bleeding and all-cause mortality. Outcomes were assessed at 3 months, 6 months, 1 year, and 5 years following the index event. At 3 months, stroke incidence was significantly higher among patients with AF and malignancy compared with AF alone (OR 2.092; CI 1.990–2.200). This increased risk persisted at 6 months (OR 1.978), 1 year (OR 1.795), and 5 years (OR 1.585). Mortality and major bleeding rates were also consistently higher in the AF and malignancy cohort across all time intervals. Patients with AF and malignancy demonstrated a significantly higher risk of ischemic stroke despite matching for established CHA₂DS₂VASc risk factors, supporting malignancy as a potential independent contributor to stroke risk. Mortality and major bleeding were likewise higher, reflecting the combined burden of malignancy and AF. The relative odds of ischemic stroke exceeded those of major bleeding across all time points. Future studies should evaluate whether incorporating malignancy into the CHA₂DS₂VASc score improves stroke risk stratification in this population.