Low, lower, the lowest? – Which LDL-cholesterol level shall we target?

By Antje Schmidt-Pogoda, Fachärztin für Neurologie, Klinik für Neurologie mit Institut für Translationale Neurologie, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, Gebäude A1, 48149 Münster

Ten years ago, the Stroke Prevention by Aggressive Reduction in Cholesterol Level (SPARCL) trial showed that high-dose statin treatment (Atorvastatin at a dose of 80 mg per day) resulted in a significantly reduced stroke recurrence rate.1 Since then, a large proportion of patients with stroke of assumed atherosclerotic origin have received statins for secondary stroke prevention. However, there has been no evidence-based LDL-cholesterol (LDL-C) target and the choice of drug and dosing regimen have been at the discretion of the attending physicians.

Only now, the Treat Stroke to Target (TST) trial sheds more light on this important issue. In TST, 2.860 patients with ischemic stroke or transient ischemic attack and evidence of cerebrovascular or coronary-artery atherosclerosis were randomly assigned to a target LDL-C level of < 70 mg/dl  (1.8 mmol per liter, higher-target group) or to a target range of 90 to 110 mg/dl (2.3 to 2.8 mmol per liter, lower-target group). These LDL cholesterol goals were achieved in both groups: In the lower-target group, the mean LDL cholesterol level was 65 mg/dl. In the higher-target group, the mean cholesterol level was 96 mg/dl.2

After a median follow-up of 3.5 years, the composite primary end point of ischemic stroke, myocardial infarction, necessity of urgent coronary or carotid revascularization and death from cardiovascular causes 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).2 TST thus demonstrates that patients with ischemic stroke and evidence of atherosclerotic disease benefit from intensive LDL-C lowering.

These findings are in line with recently updated joint guidelines of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS), which also recommend lower LDL-C goals than previous guidelines.3 For secondary prevention in very-high-risk patients, the ESC/EAS guidelines recommend an LDL-C reduction of ³ 50% from baseline and an LDL-C goal of < 55 mg/dl (1.4 mmol/L). For individuals at high risk, the ESC/EAS guidelines recommend an LDL-C reduction of  ³ 50% from baseline and an LDL-C goal of < 70 mg/dl (1.8 mmol/L), and for individuals at moderate risk, the ESC/EAS guidelines recommend an LDL-C goal of < 100 mg/dl (2.6 mmol/L).3

Altogether, there is good reason to target LDL-C levels < 70 mg/dl (1.8 mmol/L) in stroke patients with atherosclerotic disease. It remains to be explored, though, if stroke patients with non-atherosclerotic origin will also benefit from intensive cholesterol lowering.



  1. Amarenco P, Bogousslavsky J, Callahan A, 3rd, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549-559
  2. Amarenco P, Kim JS, Labreuche J, Charles H, Abtan J, Bejot Y, et al. A comparison of two ldl cholesterol targets after ischemic stroke. N Engl J Med. 2019
  3. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 esc/eas guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur Heart J. 2019