Stroke Risk Reduction in Migraine Patients Using Propranolol: Evidence from Two Large-Scale Real-World Data Analyses

Propranolol, a non-selective beta-blocker, is commonly used for migraine prevention, but its impact on stroke risk among migraine patients remains controversial. Using two large electronic health records-based datasets, we examined stroke risk differences between migraine patients with- and without- documented use of propranolol.

This retrospective case-control study utilized EHR data from the Vanderbilt University Medical Center (VUMC) and the All of Us Research Program. Migraine patients were first identified based on the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria using diagnosis codes. Among these patients, cases were defined as those with a primary diagnosis of stroke following the first diagnosis of migraine, while controls had no stroke after their first migraine diagnosis. Logistic regression models, adjusted for potential factors associated with stroke risk, assessed the association between propranolol use and stroke risk, stratified by sex and migraine subtype. A Cox proportional hazards regression model was used to estimate the hazard ratio (HR) for stroke risk at 1, 2, 5, and 10 years from baseline.

In the VUMC database, 378 cases and 15,209 controls were identified, while the All of Us database included 267 cases and 6,579 controls. Propranolol significantly reduced stroke risk in female migraine patients (VUMC: OR=0.52, p=0.006; All of Us: OR=0.39, p=0.007), but not in males. The effect was more pronounced for ischemic stroke and in females with migraines without aura (MO) (VUMC: OR=0.60, p=0.014; All of Us: OR=0.28, p=0.006). The Cox model showed lower stroke rates in propranolol-treated female migraine patients at 1, 2, 5, and 10 years (VUMC: HR=0.06-0.55, p=0.0018-0.085; All of Us: HR=0.23, p=0.045 at 10 years).

Propranolol is associated with a significant reduction in stroke risk, particularly ischemic stroke, among female migraine without aura patients. These findings suggest that propranolol may benefit stroke prevention in high-risk populations.