Lower LDL Cholesterol Levels to Reduce Cardiovascular Events After Ischemic Stroke

The Treat Stroke to Target randomized controlled trial investigated two LDL-C targets for secondary prevention in patients who recently experienced an ischemic stroke or transient ischemic attack (TIA) and had atherosclerosis. Participants were assigned to either a lower LDL-C target (<70 mg/dL) or a higher target (90-110 mg/dL), using statins with or without ezetimibe.

Study Design

An international, open-label, parallel-group trial involving 2,860 patients, followed for a median of 3.5 years.
All participants had experienced an ischemic stroke or TIA within the past 3 months and had documented cerebrovascular or coronary atherosclerosis.
The primary composite endpoint consisted of ischemic stroke, myocardial infarction, urgent coronary/carotid revascularization, or cardiovascular death.

Key Findings

The mean LDL-C achieved was 65 mg/dL in the lower-target group compared to 96 mg/dL in the higher-target group.
The primary composite endpoint occurred less frequently in the lower-target group (8.5%) than in the higher-target group (10.9%).
This result corresponds to a statistically significant hazard ratio of 0.78 (95% CI, 0.61-0.98; P = 0.04), indicating a 22% relative risk reduction in major cardiovascular events with more aggressive LDL-C lowering.
The rates of intracranial hemorrhage and new-onset diabetes were similar between the groups.

Clinical Implications

For patients with recent ischemic stroke or TIA and underlying atherosclerosis, more intensive LDL-C lowering (<70 mg/dL) is more effective than a moderate LDL-C target (90-110 mg/dL) in reducing the risk of recurrent vascular events.
The safety profile was not significantly different between the two strategies.

Bottom Line

For secondary prevention after ischemic cerebrovascular events in patients with atherosclerosis, aggressive LDL-C reduction to <70 mg/dL provides superior cardiovascular protection compared to a higher LDL-C target. This supports current guidelines that emphasize intensive lipid lowering in high-risk cerebrovascular patients.