Cancer as independent risk factor for ischemic stroke in low-risk patients with atrial fibrillation: Swedish national cohort study

Abstract Background Emerging evidence suggests that comorbid conditions not accounted for in the CHADS-VA score, such as cancer, may serve as additional and independent risk factors for an increased incidence of ischemic stroke (IS) in patients with atrial fibrillation (AF). Objective The objective of this study is to examine the incidence of IS in patients diagnosed with both AF and cancer, compared to age- and sex-matched controls with cancer, without AF. Methods Data were obtained from the Swedish health registers to identify all patients diagnosed with AF but without prior cardiovascular comorbidities between 1987 and 2018. These patients were matched with controls of the same age and sex who did not have AF. Within this cohort, individuals with a cancer diagnosis were identified using the International Statistical Classification of Diseases (ICD). The risk of IS was assessed using Cox regression models, comparing patients with AF and cancer to their matched controls at one-year and five-year follow-up intervals, as well as over the entire follow-up period (3-32 years). Patients with AF and their respective controls were stratified into six age groups based on their age at baseline. Results A total of 127,315 low-risk patients with AF and 253,195 age- and sex-matched controls without AF were identified. 49,323 individuals (39%) in the AF group were diagnosed with cancer and 80,912(32%) in the control group throughout the entire follow-up period. During the first year of follow-up, the risk of IS was more than three times higher in patients with both AF and cancer compared to controls without AF (hazard ratio HR: 3.27, 95% confidence interval CI: 2.84–3.75). Over the entire follow-up period, this risk remained significantly elevated, compared to controls (HR: 2.16, 95% CI: 2.07–2.25). The risk of IS was higher in women than in men with AF and cancer compared to their respective controls, particularly during the first year following AF diagnosis (HRwomen: 4.42, 95% CI: 3.63–5.39; HRmen: 2.35, 95% CI: 1.93–2.87). The incidence and risk of ischemic stroke increased with age in patients with AF and cancer, and was significantly higher in these patients above 50 years of age (Table, Panel A-C). Conclusion This large, nationwide, register-based cohort study demonstrates that the overall risk of IS in low-risk patients with AF and a cancer diagnosis is more than twice as high compared to controls without AF. The highest risk was observed during the first year following AF diagnosis, particularly among women and middle-aged adults (50–59 years), a population that is typically not prescribed anticoagulant therapy. These findings underscore the need for further research to evaluate the risks and benefits of anticoagulant treatment in patients with both cancer and AF.