Manya Khrlobyan, DO, MS

Amarenco P, Kim JS, Labreuche J, Charles H, Giroud M, Lee BC, Mahagne MH, Nighoghossian N, Steg PG, Vicaut E, et al. Benefit of Targeting a LDL (Low-Density Lipoprotein) Cholesterol <70 mg/dL During 5 Years After Ischemic Stroke. Stroke. 2020;51:1231–1239.

The most recent American Heart Association/American Stroke Association guidelines recommend high intensity statin therapy for patients with ischemic stroke or TIA presumed to be of atherosclerotic origin and a Low-Density Lipoprotein (LDL) level >100 mg/dL. These recommendations are largely based on the results of the 2006 SPARCL trial (Stroke Prevention by Aggressive Reduction in Cholesterol Level). With these recommendations in mind, patients are typically started on Atorvastatin 80 mg daily, though often times without a specific LDL target in mind.

The TST trial (Treat Stroke to Target) was a randomized, event driven trial which investigated the benefit of targeting an LDL of <70 mg/dL in ischemic stroke patients in a French and Korean population to reduce the risk of cardiovascular events. Patients were eligible if they had an ischemic stroke <3 months previously or a TIA within the previous 15 days, atherosclerotic stenosis of cerebral vasculature (extra or intracranial), aortic arch plaque >4 mm, or known history of coronary artery disease. Patients were randomly assigned in a 1:1 ratio to target LDL of < 70 mg/dL or target LDL of 100 + 10 mg/dL. Investigators were free to use any type and dose of statin to reach the target LDL and, at 3 weeks follow-up, had an option of adjusting the statin dose or adding other lipid lowering agents such as ezetimibe to achieve the target LDL. The primary endpoint was the composite of ischemic stroke, myocardial infarction, need for carotid or coronary revascularization, and unexplained sudden death.

In France, a total of 2148 patients were enrolled, and in South Korea, 712 patients were enrolled, with a median follow up of 5.3 year and 2 years, respectively. There was no observed risk reduction in the subjects followed during the study period in Korea.  Given the longer follow-up of 5.3 years, the French cohort results are reported in this study. The lower target group had an average LDL of 66 mg/dL, and the higher target group had an average LDL of 96 mg/dL. The primary outcome occurred in 9.6% of patients in the lower target group vs 12.9% in the higher target group (p=0.015). There was also a 25% reduction in cerebral infarction and acute cerebral artery revascularization, and a 28% reduction in cerebral infarction or intracranial hemorrhage with an absolute risk reduction of 2.9% and NNT of 34. There was no difference in intracranial hemorrhages (p=0.70). The findings in this current study are similar to a post hoc analysis of the SPARCL trial which found that patients with an LDL <70 mg/dL had a 28% relative risk reduction in stroke recurrence compared to those with an LDL of 100 mg/dL or above during a 5-year follow-up. In addition, it offered further confirmation that lowering LDL cholesterol to < 70 mg/mL did not increase the risk of intracranial hemorrhage. With this trial in mind, stroke neurologists and general practitioners should encourage their patients with ischemic stroke or TIA and underlying atherosclerotic disease to reach a target LDL of <70 mg/mL and using  additional agents such as ezetimibe are an option to help patients reach goal LDL targets.