Statin treatment and cerebral microbleeds: A systematic review and meta-analysis

Although statins have been associated with increased risk of spontaneous intracerebral hemorrhage, their relationship with cerebral microbleeds (CMBs) formation is poorly understood. We systematically reviewed previously published studies reporting on the association between CMBs presence and current statin use. We performed a systematic search in MEDLINE and SCOPUS databases on October 24, 2019 to identify all cohorts from randomized-controlled clinical trials or observational studies reporting on 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. Random effects model was used to calculate the pooled estimates. We included 7 studies (n = 3734 participants): unselected general population [n = 1965], ischemic stroke [n = 849], hemorrhagic stroke [n = 252] and patients with hypertension over the age of 60 [n = 668]. Statin use was not associated with CMBs presence in either unadjusted (OR = 1.15, 95%CI: 0.76-1.74) or adjusted analyses (OR = 1.09, 95%CI: 0.64-1.86). 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 lobar CMBs presence, considerable heterogeneity was present in all other analyses (I² > 60%). Our findings suggest that statin treatment seems not to be 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.