The effect of statins on the risk of bleeding in cerebral cavernous malformations: A systematic review and meta-analysis

Background: Cerebral cavernous malformations (CCMs) are vascular lesions composed of abnormally dilated capillaries. Although primary treatment for high-risk CCMs is surgery, it may cause significant morbidity, particularly for lesions in eloquent or brainstem areas. Therefore, statins have recently been proposed as potential stabilizing agents. This study aimed to evaluate statins in reducing the risk of (re-)bleeding in sporadic or familial CCMs. Methods: This study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in PROSPERO (CRD420250655605). PubMed/MEDLINE, Embase, Cochrane Central, and Scopus were screened from inception to August 27, 2025, for studies including patients with sporadic or familial CCMs and documented statin exposure. The primary outcome was the hazard ratio for (re-)bleeding during follow-up, comparing statin-exposed and nonexposed groups. The secondary outcome was the odds of hemorrhagic presentation at diagnosis. Random-effects meta-analyses were performed. Results: Seven studies with 2524 patients, 315 of whom used statins (10.4%), were included in the analyses. Statin use was associated with a reduced hazard of prospective (re-)bleeding in adjusted analyses (hazard ratio HR 0.419; 95% confidence interval CI 0.186, 0.942). The association remained significant when the unadjusted study was included (HR 0.523; 95% CI 0.272, 0.997). No significant difference was observed regarding hemorrhagic presentation at diagnosis (odds ratio 0.827; 95% CI 0.595, 1.162). Conclusion: Statin exposure is associated with a reduced risk of (re-)bleeding during follow-up in patients with CCMs but does not appear to influence presentation with hemorrhage at diagnosis. This suggests a potential stabilizing effect of statins on CCM bleeding beyond their established role in cardiovascular disease.