A Systematic Review and Meta-Analysis of Statins in Animal Models of Intracerebral Hemorrhage.

BACKGROUND

Intracerebral hemorrhage (ICH) is a severe form of stroke with limited treatment options. Statins have shown promise as a therapy for ICH in animal and human studies. We systematically reviewed and assessed the quality of preclinical studies exploring statin-use after ICH to guide clinical trial decision-making and design.

METHODS

We identified preclinical trials assessing the efficacy of statins in ICH via a systematic review of the literature according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In total, 16 studies were identified that described statin use in an animal model of ICH and assessed histological outcomes, behavioral scores, or both. Design characteristics were analyzed using Stroke Therapy Academic Industry Roundtable (STAIR) criteria modified for ICH. Meta-analysis was performed using a random effects model.

RESULTS

Behavioral outcomes were assessed in 12 of the studies with 100% (n = 12) reporting that statins significantly improved ICH recovery. Histologic hematoma volume and brain water content outcomes were analyzed in 10 of the studies, with 50% (n = 5) reporting significant improvement. The ratio of means between experimental and control cases for modified Neurological Severity Score was 0.63 (95% confidence interval 0.49-0.82). The ratio of means between experimental and control cases for hemorrhagic volume was 0.85 (95% confidence interval 0.70-1.03). There was heterogeneity between studies (P < 0.0001) but no evidence of publication bias (P = 0.89, P = 0.59, respectively).

CONCLUSIONS

Behavioral outcomes in ICH were found to consistently improve with administration of statins in preclinical studies suggesting that statin therapy may be suitable for randomized clinical trials in humans. In addition, the STAIR criteria can be modified to effectively evaluate preclinical studies in ICH.