Statin Treatment And Prevalent Cerebral Microbleeds: A Systematic Review And Meta-Analysis

Introduction: Statins have been reported to increase the risk of intracererbral hemorrhage, however their effects on cerebral microbleeds (CMBs) formation is not well understood. We systematically reviewed previously published studies to pool adjusted and unadjusted estimates of the association between prevalent CMBs and current statin use. Methods: We performed a systematic search in MEDLINE and SCOPUS databases on July 28 th , 2019 to identify all cohorts from randomized clinical trials or observational studies reporting CMB prevalence and statin use. We extracted cross-sectional data on CMBs presence, as provided by each study, in association to the history of current statin use. Associations are reported as odds ratios (ORs) with corresponding 95% confidence intervals (95%CI). Random effects model was used to calculate the pooled estimates. Results: We included 7 studies (n=3671 participants): unselected general population [n=1965], ischemic stroke [n=770], hemorrhagic stroke [n=252], hypertension [n=605] or neuroimaging based studies [n=72]. Statin use was not associated with CMBs presence in either unadjusted (OR=1.15, 95%CI: 0.76-1.74) or adjusted analyses (OR=1.01, 95%CI: 0.62-1.64). Statin use was more strongly related to lobar CMB presence (OR=2.01, 95%CI: 1.48-2.72) in unadjusted analysis. The effect size of this association was consistent, but no longer statistically significant in adjusted analysis that was confined to two eligible studies (OR=2.26, 95%CI: 0.86-5.91). Except for the analysis on the unadjusted probability of CMBs presence, considerable heterogeneity was present in all other analyses (I 2 >60%). Conclusion: Our findings suggest that statin treatment is not associated with CMBs overall, but may increase the risk of lobar CMB formation. This hypothesis deserves further investigation within magnetic resonance imaging ancillary studies of randomized trials.