Beta-blockers improve neurological outcomes of cerebral cavernous malformations: a systematic review

Cerebral cavernous malformations (CCMs) are vascular lesions in the brain, presenting risks of intracerebral hemorrhage (ICH) and non-hemorrhagic focal neurological deficit (NH-FND). Currently, no effective medical therapy exists for CCMs, and treatment options limited to surgical resection and stereotactic radiosurgery. Beta-blockers, particularly propranolol, have shown promise in treating similar vascular conditions and may have therapeutic potential for CCMs. We conducted a systematic search of PubMed, Web of Science, EMBASE, Cochrane Central, and ClinicalTrials.gov (March 2024) for randomized clinical trials (RCTs) and cohort studies comparing neurological outcomes in adult patients with CCMs treated with beta-blockers versus controls. Meta-analysis was performed using Review Manager 5.4. The primary outcomes were the incidence of new-onset ICH and NH-FND attributable to CCMs. Five studies (1 RCT and 4 cohort studies; n = 1,553 participants) met the inclusion criteria. Beta-blocker exposure was associated with significantly lower odds of new-onset ICH or NH-FND attributable to CCMs (OR 0.52; 95% CI 0.35-0.77; p = 0.001), with low heterogeneity (I² = 35%). Subgroup analysis showed a reduced incidence of new ICH alone (OR 0.60; 95% CI 0.39-0.91; p = 0.02). In propranolol-specific analyses, the reduction in the primary outcome was not statistically significant (OR 0.33; 95% CI 0.08-1.38; p = 0.13). Beta-blocker therapy was associated with improved neurological outcomes in patients with CCMs, with a significant reduction in the risk of new-onset ICH and NH-FND. However, propranolol alone did not demonstrate a statistically significant benefit, potentially due to subtherapeutic dosing and adverse effects. The evidence suggests other beta-blockers may also be beneficial, but further research is needed to clarify their roles and optimal regimen.