Sex- and age-specific risk of ischemic stroke in patients with atrial fibrillation and cancer: a nationwide register-based study

Background Advances in oncological therapies have markedly improved survival among patients with cancer. However, both malignancy and cancer treatment are associated with atrial fibrillation (AF) and ischemic stroke 1. Although the conventional CHA₂DS₂-VA score incorporates established stroke risk factors, its predictive performance in patients with cancer may be limited 2. Purpose To determine whether ischemic stroke risk in patients with AF and breast cancer, lung cancer, hematological malignancies, or gastrointestinal malignancies differs by age and sex. Methods Using Swedish national health registers, we identified adult patients diagnosed with the specified cancers based on ICD codes. Within this cohort, patients with prevalent AF at baseline and those who developed incident AF during follow-up (up to 55 years) were identified. Patients with cancer and AF were matched by cancer type, sex, and age decade to patients without AF. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) for ischemic stroke stratified by age and sex. Results A total of 661,523 patients were included: 36% had breast cancer, 22% lung cancer, 5% hematological malignancies, and 37% gastrointestinal malignancies. AF was present in 23% of patients with breast cancer, 16% with lung cancer, 31% with hematological malignancies, and 19% with gastrointestinal malignancies. Across all cancer types, women with AF had a higher incidence of ischemic stroke than men during follow-up of up to 55 years. Among women, HRs were 4.4 (4.3–4.6) for breast cancer, 3.4 (3.0–3.8) for lung cancer, 3.6 (3.1–4.3) for hematological malignancies, and 4.6 (4.3–4.9) for gastrointestinal malignancies. Corresponding HRs in men were 2.6 (2.3–2.9) for lung cancer, 2.7 (2.4–3.1) for hematological malignancies, and 3.4 (3.2–3.6) for gastrointestinal malignancies. Patients younger than 65 years with cancer and AF had a higher relative risk of ischemic stroke than those aged ≥65 years. In patients <65 years, HRs were 3.3 (3.1–3.6) for breast cancer, 3.7 (3.1–4.4) for lung cancer, 3.4 (2.7–4.3) for hematological malignancies, and 4.5 (4.1–4.9) for gastrointestinal malignancies. Corresponding HRs in patients ≥65 years were 2.8 (2.6–3.0), 2.5 (2.2–2.8), 2.6 (2.2–3.0), and 3.0 (2.8–3.4), respectively. Conclusion AF is common among patients with cancer and is associated with a disproportionately elevated relative risk of ischemic stroke in women and in patients younger than 65 years. These findings suggest important limitations of current stroke risk stratification models in the oncology setting and support the need for sex- and age-specific risk assessment, as well as careful reconsideration of anticoagulation strategies in patients with cancer and AF.