Influenza vaccination and ischemic stroke risk reduction in elderly stroke survivors: a retrospective cohort study with negative control validation

Abstract Background and objectives Stroke is a leading cause of disability and mortality among older adults, with high recurrence rates. Currently, there’s limited research reporting on the protective effect of influenza vaccination against recurrent stroke in elderly stroke survivors. This study aimed to evaluate the association between influenza vaccination and stroke risk in this group. Methods A retrospective cohort study was conducted using data from the Ningbo Regional Health Information Platform. Eligible participants were adults aged ≥ 65 years with a history of stroke, registered in the platform for ≥ 1 year by December 31, 2021. Follow-up ended at stroke occurrence, death, or July 31, 2022, whichever occurred first. The primary outcome was any stroke event. Exposure was defined as influenza vaccination during the 2021–2022 season. Adjusted subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) were estimated using Fine-Gray competing risk models. Pneumococcal vaccination was included as a negative control outcome. Results Among 76,747 participants, 31,729 (41.3%) received influenza vaccination. Over 7 months, 6,323 stroke events occurred: 5,631 ischemic, 653 hemorrhagic, and 39 unspecified. After adjusting for demographics and comorbidities, influenza vaccination was associated with a reduced risk of ischemic stroke among elderly stroke survivors (particularly those whose last stroke event occurred ≥ 1 year prior) (adjusted sHR: 0.90, 95% CI: 0.85–0.95) but showed no significant association with hemorrhagic stroke risk (adjusted sHR: 0.89, 95% CI: 0.76–1.05). Additionally, influenza vaccination demonstrated significant protective effects against both cardiogenic stroke (adjusted sHR: 0.74, 95% CI: 0.63–0.86) and non-cardiogenic stroke (adjusted sHR: 0.93, 95% CI: 0.88–0.98), with a stronger protective effect observed for cardiogenic stroke. Conclusion Influenza vaccination is associated with lower ischemic stroke risk among elderly stroke survivors, independent of cardiogenic etiology. These findings suggest a potential nonspecific preventive benefit and highlight the need for randomized trials to establish causality and inform clinical guidelines for stroke survivors.