Age-dependent effects of SGLT2 inhibitors on stroke risk in geriatric patients with diabetes and atrial fibrillation

Abstract

Abstract Background Atrial fibrillation (AF) and diabetes mellitus (DM) are associated with an increased risk of ischemic stroke, particularly in geriatric populations. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated cardiovascular benefits, but their effects on stroke risk may vary by age. This study aimed to explore the age-dependent effects of SGLT2i on stroke risk in patients with AF and DM. Methods This historical longitudinal follow-up cohort study included 9,669 patients with AF and DM from the National Taiwan University Hospital database (2010–2020). Patients were stratified into three age groups (< 75, 75–89, and ≥ 90 years) to compare SGLT2i users and non-users within each age group. Cox proportional hazards models were used to evaluate stroke risk, adjusting for CHA₂DS₂-VASc score and oral anticoagulant use. Interaction analysis assessed age-specific SGLT2i effects. Results In patients aged < 75 years, SGLT2i use significantly reduced stroke risk (HR 0.63, 95% CI 0.44–0.88, P < 0.05). Stroke risk was neutral in patients aged 75–89 years (HR 0.95, 95% CI 0.60–1.50), but significantly increased in those aged ≥ 90 years (HR 5.04, 95% CI 1.20–21.1, P < 0.05). Interaction analysis confirmed a significant age-dependent effect (aged ≥ 90 years x SGLT2i use HR 6.39, 95% CI 1.49–27.40, P < 0.05). Conclusions The impact of SGLT2i on stroke risk varies significantly by age. While protective in younger patients, SGLT2i may increase stroke risk in those aged ≥ 90 years. These findings highlight the importance of age-specific considerations in prescribing SGLT2i for patients with AF and DM. Graphical Abstract

Keywords

• SGLT2 inhibitors
• Atrial fibrillation
• Diabetes mellitus
• Stroke
• Geriatrics