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.