Abstract Body: Introduction: Acute ischemic stroke is the second leading cause of death worldwide. Levels of LDL-C were correlated with the risk of recurrent stroke or transient ischemic attack (TIA). However, there are controversial data regarding the effect of statins on recurrent stroke across different baseline LDL levels. We aimed to assess the effect of statins across different LDL levels to prevent recurrent stroke in patients with acute ischemic stroke.

Methods: PubMed, Scopus, Web of Science, and the Cochrane Library were searched for Randomized Controlled Trials (RCTs) assessing the impact of statins across levels of baseline LDL from inception until April 2024. The primary outcome was the incidence of recurrent stroke which was categorized according to baseline LDL levels, absolute decrease in LDL levels, and percentage decrease in LDL levels. The odds ratio (OR) with its 95% confidence interval (CI) was used in a random-effect model.

Results: Eighteen RCTs comprising 175,225 patients (mean follow-up of 3 years) were included in the final analysis. Statins were associated with a reduced incidence of recurrent stroke in patients with baseline LDL <100 mg/dl, or >100 mg/dl, with the following values, respectively (OR: 0.85, 95% CI: 0.72 to 0.98, p= 0.04, and 0.88, 95% CI: 0.78 to 0.98, p= 0.03). Additional analysis in patients with an absolute decrease in LDL levels >3 mg/dl showed a lower incidence of recurrent stroke (OR: 0.85, 95% CI: 0.77 to 0.94, p <0.001). Regarding percentage decrease in LDL levels (30-49% and >50%), statins showed a lower risk of recurrent stroke, respectively as follows (OR: 0.65, 95% CI: 0.44 to 0.97, p =0.03, and 0.83, 95% CI: 0.7 to 0.98, p =0.03).

Conclusion: This study suggests that statins-based therapies were associated with recurrent stroke risk reduction across baseline LDL levels, absolute and percentage decrease in LDL levels. Additional data on the evidence of atherosclerosis might be warranted to study the impact of statins on high LDL levels in the presence of atherosclerosis.