Association of migraine treatments with reduced ischemic stroke risk: Evidence from two large-scale real-world data analyses.

Objective: To compare the risk of ischemic stroke in patients with migraine treated with first-line medications, including valproate, topiramate, metoprolol, timolol, or propranolol, versus those not receiving these treatments, using data from two large electronic health records datasets.

Background: The impact of first-line migraine medications on ischemic stroke risk in patients with migraine remains uncertain, highlighting the need for further investigation.

Methods: We conducted a retrospective case-control study using data from Vanderbilt University Medical Center (VUMC) and the All of Us Research Program. Cases were patients with a primary ischemic stroke diagnosis after their first migraine diagnosis, while controls had no ischemic stroke following their initial migraine diagnosis.

Results: In the VUMC database, 356 cases and 15,231 controls were identified; the All of Us database included 256 cases and 6590 controls. Propranolol was the only medication significantly associated with a reduced risk of ischemic stroke in female patients with migraine (VUMC: adjusted odds ratio [aOR] 0.55, 95% confidence interval [CI] 0.33-0.86, p = 0.013; All of Us: aOR 0.41, 95% CI 0.19-0.77, p = 0.010), particularly in those with migraine without aura (VUMC: aOR 0.53, 95% CI 0.29-0.90, p = 0.027; All of Us: aOR 0.28, 95% CI 0.10-0.62, p = 0.006). The Cox model showed lower ischemic stroke rates in propranolol-treated female patients with migraine at 10 years in the VUMC data (adjusted hazard ratio [aHR] 0.45, 95% CI 0.24-0.83; p = 0.011, log-rank p < 0.001) and 10 years in the All of Us data (aHR 0.29, 95% CI 0.09-0.87; p = 0.048, log-rank p = 0.003).

Conclusions: Among various migraine treatments, propranolol was notably associated with a significant reduction in ischemic stroke risk among female patients with migraine, particularly those without aura. These findings suggest a potential dual benefit of propranolol in managing migraine and reducing stroke risk, highlighting the need for further prospective studies to confirm these results and potentially inform clinical practice.