By Matthew E. Fink, MD

Feil Professor and Chairman, Department of Neurology, and Assistant Dean of Clinical Affairs, Weill Cornell Medical College; Neurologist-in-Chief, New York Presbyterian Hospital

Dr. Fink reports no financial relationships relevant to this field of study.

SOURCE: Amarenco P, Kim JS, Labreuche J, et al. Benefit of targeting LDL (low-density lipoprotein) cholesterol <70 mg/dL during 5 years after ischemic stroke. Stroke 2020;51:1231-1239.

In the SPARCL trial (N Engl J Med 2006;355:549-559), treatment of patients with atorvastatin 80 mg per day resulted in a 16% relative risk reduction in stroke during 4.9 years of follow-up, compared to placebo. In a subgroup with carotid artery stenosis, the relative risk reduction was 33%. Patients who had a low-density lipoprotein (LDL) cholesterol less than 70 mg/dL had a 28% relative risk reduction compared to patients who only achieved an LDL cholesterol of 100 mg/dL or above. Amarenco et al specifically focused on targeting an LDL cholesterol below 70 mg/dL in patients who had ischemic stroke or transient ischemic attack (TIA) with evidence of atherosclerosis. The patients were stratified into two groups, where statins were titrated to reach an LDL cholesterol of less than 70 mg/dL or with an LDL of 100 mg/dL. Investigators were free to use any statin of their choice, and this could be combined with ezetimibe or other medications as needed. This was an open-label trial, and patients and investigators were not blinded to treatments. The primary endpoint was the composite of nonfatal stroke, nonfatal myocardial infarction, unstable angina, TIA, and vascular death. Patients were enrolled from 2010 until 2018. The study ended early, after 277 primary endpoints were accrued, because of a lack of funds. Median follow-up was 3.5 years. The groups achieved mean LDL cholesterol of 66 mg/dL and 96 mg/dL, respectively. The primary endpoint occurred in 9.6% and 12.9% of patients, respectively, with a hazard ratio in favor of lower cholesterol of 0.74 (P = 0.019). Ischemic stroke or urgent carotid revascularization following TIA was reduced by 27%. The primary outcome was reduced by 25%. There was no significant difference in the numbers of intracranial hemorrhages that occurred between the two groups. The investigators concluded that after an ischemic stroke of atherosclerotic origin, targeting LDL cholesterol to less than 70 mg/dL resulted in a significant reduction in subsequent major vascular events and no increase in intracranial hemorrhage.