Impact of Lower vs Higher LDL Cholesterol Targets on Cardiovascular Events After Ischemic Stroke in Diabetic Patients
Patients with ischemic stroke in the previous 3 months or TIA within the previous 15 days and evidence of cerebrovascular or coronary artery atherosclerosis were randomly assigned in a 1:1 ratio to a target LDL cholesterol of less than 70 mg/dL or 100±10 mg/dL, using statin or ezetimibe. The primary outcome was the composite of ischemic stroke, myocardial infarction, new symptoms requiring urgent coronary or carotid revascularization and vascular death. We did a pre specified analysis to evaluate the effect in diabetic patients.
Among 2,860 patients enrolled, 643 were diabetic at baseline with a mean age of 66.2 years and baseline LDL cholesterol of 127 mg/dL and were followed for a median of 3 years. The primary composite endpoint occurred in 27/328 (8.2%) patients in the lower target group and in 44/315 (14.0%) patients in the higher target group (adjusted hazard ratio, 0.56 [95% CI, 0.34 to 0.89]; P=0.016), while hazard ratio was 0.87 (95% CI, 0.66 to 1.14; P=0.31) in nondiabetic patients (Pinteraction=0.15). In diabetics, there were 3 intracranial hemorrhages in both randomization groups (0.9% vs. 1.0%, respectively). Newly diagnosed diabetes occurred in 98/1070 (9.2%) and in 80/1085 (7.4%) patients in the lower and higher target group, respectively (HR=1.27 [95% CI, 0.94 to 1.71], P=0.11) and baseline higher HbAIc was the unique multivariable predictor.
In conclusions, after an ischemic stroke with evidence of atherosclerosis, targeting an LDL cholesterol of less than 70 mg/dL compared to 100±10 mg/dL consistently reduced the risk of subsequent stroke and other major vascular events in diabetic and nondiabetic patients, but the higher risk in diabetic patients yielded a higher absolute risk reduction with an NNT of 17 (ClinicalTrials.gov NCT01252875- EUDRACT Identifier number 2009-A01280-57).