Ischemic stroke in patients with cancer: impact of atrial fibrillation in a nationwide register-based study

Background

Advances in cancer therapy have improved survival, resulting in a growing population at risk of cardiovascular complications. Cancer is associated with atrial fibrillation (AF), ischemic stroke, and heart failure, but long-term data on ischemic stroke risk across different cancer types in patients with concomitant AF are limited 1,2.

Purpose

To evaluate the risk of ischemic stroke in patients with AF and breast cancer, lung cancer, hematological malignancies, or gastrointestinal malignancies.

Methods

Using Swedish national health registers, we identified adults diagnosed with the specified cancers based on ICD codes 3. Patients with prevalent AF at cancer diagnosis (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 models estimated hazard ratios (HRs) for ischemic stroke. Follow-up began at cancer diagnosis (or at AF diagnosis for incident AF) and continued until death, emigration, or study end. Secondary outcomes were heart failure and cardiovascular mortality. Cardiovascular comorbidities were assessed at baseline.

Results

A total of 661,523 patients were included: 240,773 with breast cancer (29,732 [12%] with AF), 145,720 with lung cancer (23,558 [16%]), 32,836 with hematological malignancies (10,200 [31%]), and 242,194 with gastrointestinal malignancies (45,194 [19%]). Follow-up was longest in breast cancer (Table 1).

Across all cancer types, AF was associated with higher ischemic stroke risk compared with no AF (9% vs 2.7%). Risk was consistently higher in patients who developed AF during follow-up than in those with AF at baseline. In breast cancer, HRs for ischemic stroke were 2.9 (2.7–3.2) for baseline AF and 4.2 (4.1–4.4) for incident AF. Corresponding HRs were 1.6 (1.4–1.8) and 3.5 (3.2–3.9) in hematological malignancies; 1.4 (1.3–1.6) and 4.5 (4.1–4.9) in lung cancer; and 2.0 (1.8–2.1) and 4.1 (4.0–4.3) in gastrointestinal malignancies. Overall stroke risk was highest in breast cancer with AF (HR 4.4 [4.3–4.6]), followed by gastrointestinal (HR 3.9 [3.7–4.0]), hematological (HR 3.0 [2.7–3.3]), and lung cancer (HR 2.9 [2.7–3.2]). Heart failure was most frequent in breast cancer patients with AF, and cardiovascular mortality was approximately threefold higher in patients with AF across all cancer types (Table 2).

Conclusion

In patients with breast, lung, hematological, or gastrointestinal cancers, concomitant AF was associated with a significantly increased risk of ischemic stroke during follow-up, particularly when AF developed after cancer diagnosis. AF was also linked to higher rates of heart failure and cardiovascular mortality. These findings highlight the importance of continuous cardiovascular risk assessment in patients with cancer and AF.