To evaluate the efficacy and safety of statins in the acute phase of ischemic stroke (IS).

Stroke is a neurological condition with major impact worldwide due to its mortality, morbidity and high costs to the healthcare system. While statins are well-established for secondary prevention of atherosclerotic stroke, their efficacy and safety in the acute phase remain uncertain.

We searched PubMed, Embase and Cochrane for randomized controlled trials (RCTs) comparing statins against placebo or standard care in the acute phase of IS. The protocol was registered on PROSPERO (CRD42024582508). The primary outcomes included new ischemic stroke, hemorrhagic transformation,  the combination of hemorrhagic stroke and hemorrhagic transformation, and optimal functional outcome, defined as modified Rankin Scale scores (mRS) < 2. The secondary outcomes included good functional outcome (mRS ≤ 2), NIHSS improvement (reduction ≥ 4), all-cause mortality, musculoskeletal adverse events, transaminases elevation and a composite outcome including any stroke (ischemic or hemorrhagic), myocardial infarction and vascular death. Heterogeneity was assessed with I² and a random-effects model. Statistical analysis was performed using Review Manager 8.7.0.

We included 7212 patients from 10 RCTs, of whom 63% were men. Among these, 3604 received statins in the acute phase. Strokes from all TOAST classification were included in the analysis. Statins were associated with an optimal functional outcome (RR 1.02 [1.00–1.04], p=0.03), but showed no significant association with good functional outcome  (RR 1.01; [0.99–1.02], p = 0.33) or NIHSS improvement  (RR 1.14; [0.64–2.03], p=0.65). No significant differences in safety outcomes were observed between groups.

Our findings suggest that statins are safe in the acute phase of ischemic stroke and may be associated with optimal functional outcome.