Migraine Therapy Propranolol Shows Potential to Reduce Stroke Risk

You Chen, PhD

Credit: VUMC

Evidence from 2 large-scale, real-world data analyses revealed that propranolol, a beta-blocker medication, was associated with a significant attenuation in the risk of ischemic stroke among female patients with migraine, particularly those with aura. Investigators concluded that future research should prioritize prospective studies to validate these findings and investigate the mechanisms behind propranolol’s protective effects.¹

Published in Headache, the retrospective case-control study comprised 356 cases of primary ischemic stroke diagnosis and 15,231 controls from the Vanderbilt University Medical Center (VUMC) database. Led by You Chen, PhD, an associate professor of biomedical informatics at VUMC, the study looked at 5 first-line migraine treatments: valproate, topiramate, metoprolol, timolol, and propranolol, in the context of stroke risk among patients with migraine.

In the VUMC electronic health record (ECR) database, none of the migraine treatments showed a significant association with the risk of ischemic stroke in males; however, propranolol was significantly associated with a reduced risk of ischemic stroke in females (adjusted OR [aOR], 0.55; 95% CI, 0.33-0.86; P = .013). In the All of Us Research EHR database, propranolol was significantly associated with a reduced risk of ischemic stroke in females (aOR 0.41, 95% CI 0.19–0.77; p = 0.010), while no migraine treatments showed significant associations in males. Stratified analysis by migraine type revealed that females with migraine without aura (MO) who used propranolol had significantly lower odds of ischemic stroke, as shown in covariate-adjusted models from both EHR databases (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).

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"Despite differences in patient demographics and clinical characteristics between the VUMC and All of Us cohorts, the association between propranolol and reduced ischemic stroke risk in females remained significant," Chen et al wrote. "The significant reduction in ischemic stroke risk observed with propranolol may be attributed to its unique pharmacological profile beyond its effects on blood pressure and HRV. While other β-blockers, such as metoprolol and timolol, were included in the study, propranolol demonstrated a more pronounced protective effect against ischemic stroke."

The VUMC database showed that female patients with migraine treated with propranolol had a lower cumulative incidence of ischemic stroke compared to non-treated patients at each time point: 0.3% vs. 1.2% at 1 year, 0.4% vs. 1.5% at 2 years, 0.4% vs. 1.7% at 5 years, and 0.9% vs. 2.0% at 10 years. Adjusted hazard ratios indicated a significantly lower stroke risk in the propranolol group at 1, 2, and 10 years (P < 0.05), but no significant difference at 5 years (P = 0.118).

In the All of Us database, female migraine patients treated with propranolol had a lower cumulative incidence of ischemic stroke compared to non-treated patients at all time points: 0% vs. 1.1% at 1 year, 0% vs. 1.5% at 2 years, 0% vs. 2.3% at 5 years, and 0.9% vs. 3.3% at 10 years. The adjusted hazard ratio at 10 years was 0.29 (95% CI 0.09–0.87; P = 0.048), with a log-rank P = 0.003, though no ischemic stroke events were observed in the propranolol group at 1, 2, and 5 years.

This study had several limitations. First, it was based on a retrospective administrative dataset, which limited the ability to account for un-coded diagnoses and infer causality. The reliance on ICD codes for migraine and ischemic stroke diagnoses may have also introduce misclassification bias. Although the sample size was large, the low incidence of ischemic stroke events and exclusion of many covariates reduced statistical power. Additionally, the underrepresentation of male patients with migraine may have further limited power to detect associations in this group. Finally, the inclusion of transient ischemic attack (TIA) in ischemic stroke data raises concerns about misclassification, as TIAs and migraines share similar symptoms and lack biomarkers for accurate differentiation.

REFERENCE
1. Jeong E, Mogos MF, Chen Y. Association of migraine treatments with reduced ischemic stroke risk: Evidence from two large-scale real-world data analyses. Headache. Published online February 14, 2025. doi:10.1111/head.14918