Supplementary Material for: Statin Therapy for Preventing Recurrent Stroke in Patients with Ischemic Stroke: A Systematic Review and Meta-analysis of Randomised Controlled Trials and Observational Cohort Studies

Introduction Statins are effective in preventing vascular disease and are widely recommended and used for the secondary prevention of ischemic stroke. However, there is concern from trials that statins might increase the risk of hemorrhagic stroke, partially reducing their benefit. We sought to systematically review the latest evidence on this question. Methods Four electronic databases were searched to identify published randomised controlled trials (RCTs) and observational cohort studies (search date December 2020). Two independent reviewers carried out the eligibility assessment based on predefined inclusion criteria. We examined the outcomes of recurrent stroke (after ischemic stroke) of any type, and separately recurrent ischemic stroke and recurrent hemorrhagic stroke. RCTs and observational cohort studies were meta-analysed separately. Odds ratios (OR) was used to assess the effect of statin therapy. Meta-analysis was conducted using RevMan 5.4 software. Results We retrieved 559 papers in searches, of which 11 RCTs and 12 observational cohort studies were included. Both RCTs and observational studies found that statins reduced the odds of stroke of any type in those with an initial ischemic stroke (11 RCTs: OR=0.87, 95% CI [0.77,0.97]; P=0.02; 12 cohort studies: OR=0.80, 95% CI [0.66, 0.96]; P=0.02). Both RCTs and observational studies found that recurrence of ischemic stroke was reduced by statins (6 RCTs: OR=0.81, 95% CI [0.70, 0.93]; P=0.002; 3 observational studies: OR=0.67, 95% CI [0.61, 0.75]; P<0.00001). Data from 7 RCTs and 8 cohort studies did not find a significant difference in hemorrhagic stroke but could not rule out a substantial increase or reduction (7 RCTs: OR=1.15, 95% CI [0.62, 2.13]; P=0.66; 8 cohort studies: OR=0.93, 95% CI [0.71, 1.21]; P=0.59). Conclusions In people who have experienced an ischemic stroke, statins reduce the risk of recurrent stroke of any type medicated through a reduction of ischemic stroke. We found no increase in the risk of hemorrhagic stroke.