Low-density Lipoprotein Cholesterol Reduction Therapies for Secondary Prevention in Patients with Stroke: A Network Meta-analysis

Background: Patients with previous strokes are at a higher risk of stroke recurrence. Current guidelines recommend a range of low-density lipoprotein cholesterol (LDL-C)-lowering treatments to reduce the risk of recurrent stroke. However, the optimal agent for decreasing LDL-C to lower the risk of recurrent stroke remains unclear. This study aimed to assess the relative effects of various LDL-C -lowering agents for secondary stroke prevention. Methods: Several databases were searched from inception up to 2022. Only randomized controlled trials that compared different LDL-C-lowering agents in adult patients with previous strokes were included. The primary endpoint was a recurrent stroke. The surface under the cumulative ranking curve (SUCRA) was also applied to estimate the overall ranking probability of the treatment agents for each outcome. Results: Overall, nine trials comprising 17,226 patients were included. Ezetimibe plus statins (RR: 0.56, 95% CrI: 0.35-0.87) and statins alone (RR: 0.90, 95% CrI: 0.81-1.00) reduced the risk of stroke recurrence. Ezetimibe plus statins was superior to statins alone in decreasing the incidence of recurrent stroke (RR: 0.62, 95% CrI: 0.39-0.95). However, treatment with statins was related to an increased risk of hemorrhagic stroke compared to placebo (RR: 1.57, 95% CrI: 1.13-2.21). All agents were related to a decreased incidence of major adverse cardiovascular events. Conclusion: Treatment with ezetimibe plus statins was suggested as the most efficacious in decreasing the incidence of recurrent stroke. The analysis also revealed that statin monotherapy was related to an increased risk of hemorrhagic stroke.