The setting of a target low-density lipoprotein (LDL) cholesterol level below 70 mg/dL in the 5 years following an ischemic stroke was associated with a 25% reduction in intracranial hemorrhages, according to study results published in Stroke.

Exposure duration of intensive statin therapy is known to correlate with a reduction in cardiovascular (CV) events. However, despite multiple guideline recommendations for such treatment following atherosclerotic ischemic stroke or transient ischemic attack (TIA), the optimal LDL target level remains unspecified.

In this sub-analysis of the Treat Stroke to Target (TST; ClinicalTrials.gov identifier: NCT01252875) trial, a randomized, event-driven study  the impact of an LDL target of <70 mg/dL on CV events was examined in 2148 French patients (>18 years) who were enrolled between March 2010 and December 2018. The cohort was divided 1:1 according to LDL cholesterol target level: <70 mg/dL (experimental group; n=1073; mean age, 67.2±11.2 years; 67.8% men) and target range of 90-110 mg/dL (control group; n=1075; mean age, 67.6±11.0 years; 68.9% men). 


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All participants had a recent ischemic stroke or TIA and had cerebrovascular atherosclerotic stenosis or aortic arch plaque (>4 mm). Clinicians prescribed whichever statin medication and dosage they deemed appropriate, with the option of adding ezetimibe, if needed.

The study’s primary outcome was the incidence of a composite of nonfatal ischemic stroke, nonfatal myocardial infarction, CV death, and urgent carotid or coronary revascularization. At each follow-up, occurring at 6-month intervals, LDL cholesterol levels were measured.

After a 5.3-year median follow-up, the mean LDL cholesterol levels were 66 mg/dL in the experimental group and 96 mg/dL in the control group. During follow-up, composite outcome occurred in 9.6% of patients with the lower LDL cholesterol target (n=103) and in 12.9% of participants with a 90-110 mg/dL target (n=139; hazard ratio [HR], 0.74 [95% CI, 0.57-0.94]; P =.019).

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There were significant reductions in patients with the lower LDL cholesterol target in the incidence of some of the components of the composite measure: cerebral infarction or urgent carotid revascularization incidence was lowered by 27% (HR, 0.73; 95% CI, 0.54-0.99; P =.046), and cerebral infarction or intracranial hemorrhage were decreased by 28% (HR, 0.72; 95% CI, 0.54-0.98; P =.023). The primary outcome or incidence of intracranial hemorrhage was 25% lower in participants <70 mg/dL vs 90-110 mg/dL with an LDL cholesterol target (HR, 0.75; 95% CI, 0.58-0.96; P =.021).

Intracranial hemorrhages occurred in 13 patients (1.2%) in the experimental group and in 11 in the control arm ((1.0%; HR, 1.17; 95% CI, 0.53-2.62; P =.70).

“The positive result of the TST trial with a number needed to treat 30 sets a new target range for LDL cholesterol to achieve of <70 mg/dL during 5 years after a stroke of atherosclerotic origin,” noted the authors.

Reference

Amarenco P, Kim JS, Labreuche J, et al. Benefit of targeting a LDL (low-density lipoprotein) cholesterol <70 mg/dL during 5 years after ischemic stroke. Stroke. 2020. doi:10.1161/STROKEAHA.119.028718