Abstract Body: Background: Migraine, a neurological disorder characterized by recurrent headaches, affects about 20% of the global population and is linked to an increased risk of stroke, particularly ischemic stroke. Propranolol, a non-selective beta-blocker, is widely used for migraine prevention, but its role in reducing stroke risk among migraine patients remains controversial.

Method: Using data from the Synthetic Derivative (SD) at Vanderbilt University Medical Center (VUMC) and the All of Us Research Program, we condcuted a retrospective case-control study. Migraine and Stroke cases were identified using International Classification Disease codes (ICD 9 and 10). Stroke cases were defined as patients with a primary diagnosis of stroke after the first onset of migraine, while controls had no stroke diagnosis after the first onset of migraine. Logistic regression models adjusted for potential confounders were used to assess the association between propranolol use and stroke risk, stratified by sex. An-adjusted Cox proportional hazards regression model was fitted to estimate the hazard ratios (HR).
Results: In the SD database, 378 cases and 15,209 controls were identified, while the All of Us database included 267 cases and 6,579 controls. Propranolol was significantly associated with a reduced risk of overall stroke in female migraine patients (SD: OR = 0.52, P = 0.006; All of Us: OR = 0.39, P = 0.007), but not in males. The protective effect was more pronounced for ischemic stroke and in females with migraines without aura. Cumulative incidence analyses showed lower stroke rates in propranolol-treated females at multiple time points within both EHR databases.
Conclusion: Propranolol is associated with a significant reduction in ischemic stroke among female migraine patients. These findings suggest that propranolol may be beneficial not only for migraine prophylaxis but also for stroke prevention in high-risk populations. Further prospective studies are warranted to validate these results and inform clinical guidelines.