Greater cardiovascular benefits with aggressive LDL-C reduction in patients with prior ischemic stroke

29 Apr 2020

The recent 2019 European Society of Cardiology/European Atherosclerosis Society Guidelines for the Management of Dyslipidemias have set a target low-density lipoprotein (LDL)-C goal of <55mg/dL for very high-risk patients requiring secondary prevention.1 For patients at high risk, a LDL-C goal of <70mg/dL is recommended.1 A log-linear relationship between the absolute change in plasma LDL-C and atherosclerotic cardiovascular (ASCVD) risk has been consistently demonstrated. The Treat Stroke to Target (TST) trial found that a LDL-C target of <70mg/dL in French patients after an ischemic stroke of documented atherosclerotic origin led to a number needed to treat of 30, and no increase in the intracranial hemorrhage.2 The results of this trial were presented at the International Stroke Conference in Los Angeles, California, on February 19-20, 2020. 

Stroke is the 4th highest cause of death in Hong Kong as of 2018.3 A high prevalence of dyslipidemia in the population translates to a larger proportion of strokes potentially attributable to this condition, and thus a greater importance to public health.4 Current recommendations for stroke prevention focus on optimizing dyslipidemia.4 Data from prospective cohort studies have shown higher risks of ischemic stroke with increasing levels of total cholesterol regardless of gender.4

The TST trial was a randomized trial that evaluated the benefit of targeting a LDL-C level of <70mg/dL to reduce the risk of cardiovascular (CV) events in French and Korean patients with ischemic stroke and atherosclerotic stenosis of cerebral vasculature or aortic arch plaque exceeding 4mm.2 Median follow-up lasted for 5.3 years in French patients, and 2.0 years in Korean patients. The results of the French cohort were reported at the International Stroke Conference.

1,073 and 1,075 French patients were set a target LDL-C goal of <70mg/dL and 90-110mg/dL, respectively. Doctors used a statin with their chosen dosage and added ezetimibe if necessary, so as to achieve these targets. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization, and vascular death.2

After a median follow-up of 5.3 years, the average achieved LDL-C levels were 66mg/dL and 96mg/dL in the target arms of <70mg/dL and 90-110mg/dL, respectively.2 The primary endpoint occurred in 9.6% and 12.9% of patients, respectively (HR=0.74; 95% CI: 0.57-0.94; p=0.019).2 The primary outcome or intracranial hemorrhage was reduced by 25% (p=0.021), with intracranial hemorrhages occurring in 13 and 11 patients, respectively (HR=1.17; 95% CI: 0.53-2.62; p=0.70). The risk of cerebral infarction or urgent carotid revascularization following transient ischemic attack was also reduced by 27% (p=0.046).2

The results of this trial demonstrated that the aggressive LDL-C reduction with a goal of <70mg/dL has led to greater CV benefits as compared to a more modest reduction with LDL-C of 90-110mg/dL in patients with ASCVD and evidence of ischemic stroke.2 

  1. Mach F et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular riskThe Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 0(0):1-78. doi:10.1093/eurheartj/ehz455
  2. Amarenco Pierre et al. Benefit of Targeting a LDL (Low-Density Lipoprotein) Cholesterol <70 mg/dL During 5 Years After Ischemic Stroke. Stroke. 0(0):STROKEAHA.119.028718. doi:10.1161/STROKEAHA.119.028718
  3. Centre for Health Protection, Department of Health - Number of Deaths by Leading Causes of Death, 2001 - 2018. Centre for Health Protection. Accessed March 6, 2020.
  4. Glasser SP et al. WHAT IS THE ASSOCIATION OF LIPID LEVELS AND INCIDENT STROKE? Int J Cardiol. 2016;220:890-894. doi:10.1016/j.ijcard.2016.06.091
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