A Comparison of Two LDL Cholesterol Targets after Ischemic Stroke.

BACKGROUND: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. RESULTS: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups. CONCLUSIONS: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).

Treat stroke to target trial design: First trial comparing two LDL targets in patients with atherothrombotic strokes.

BACKGROUND: In patients with non-cardio-embolic stroke, atorvastatin 80 mg/day reduced the relative risk of recurrent stroke by 16%, and a post hoc analysis showed that achieving an LDL-c of less than 70 mg/dL reduced the relative risk by 28% as compared to an on-treatment LDL of 100 mg/dL or more. Current guidelines from the French drug agency recommend treating with a statin after an ischaemic stroke to a target of less than 100 mg/dL, but no study directly tested LDL-c targets. The Treat Stroke to Target (TST) trial will compare the efficacy of achieving an LDL-c of less than 70 mg/dL versus an achieved LDL-c of 100 ± 10 mg/dL for secondary prevention in patients with recent ischaemic stroke of atherosclerotic origin.Main hypothesis: An achieved on-treatment LDL-c of less than 70 mg/dL will reduce by 25% the risk of recurrent ischaemic stroke, myocardial infarction, urgent coronary or carotid revascularisation following new symptoms requiring hospitalisation, and vascular death compared with on-treatment LDL-c of 100 ± 10 mg/dL. DESIGN: Patients are randomised to either LDL-c levels, and the investigator who is not blinded can use the lipid-lowering agent of his/her choice available on the market (including statins and ezetimibe), in order to achieve the assigned LDL-c level. To be eligible for enrolment, patients have a recent ischaemic stroke or TIA of atherosclerotic origin with at least one arterial stenosis of a cerebral artery, enrolled between acute phase of the qualifying stroke (once the neurological deficit is stabilised) and three months. The initial planned sample size of 3760 participants followed three years was amended to allow follow-up of all enrolled patients until 385 primary efficacy outcome events have occurred, and no later than 31 December 2019. Patients will be recruited in 76 sites in two countries (France and South Korea) between March 2010 and December 2018 (last included patient followed up to one year). Safety outcomes will include haemorrhagic strokes and new onset diabetes. All primary endpoints will be adjudicated by an endpoint committee, blinded to the assigned LDL-c level. Two sub-studies assess (1) the relative effect of assigned LDL-c levels on occurrence of new atherosclerotic plaque as detected by carotid ultrasound during follow-up, using M'ATH software for repositioning and (2) the genetic and biomarker drivers of recurrent primary endpoints according to assigned LDL-c lowering arm, in atherosclerotic strokes. SUMMARY: The TST trial is evaluating the benefits of achieving an LDL-c less than 70 mg/dL for secondary stroke prevention in ischaemic stroke patients of atherosclerotic origin. Main results are anticipated in 2020 or earlier (ClinicalTrials.gov NCT01252875).