Effect of a ≥50% Reduction in Low-Density Lipoprotein Cholesterol From Baseline in Patients With Ischemic Stroke

BACKGROUND AND OBJECTIVES: Current secondary atherosclerotic cardiovascular disease prevention guidelines recommend both a ≥50% reduction in low-density lipoprotein cholesterol (LDL-C) from baseline and an absolute LDL-C goal (<70 or <55 mg/dL). Stroke-specific guidelines primarily emphasize only an absolute LDL-C goal, and the independent clinical impact of achieving a ≥50% reduction remains unclear in patients with ischemic stroke. This study aimed to evaluate whether achieving a ≥50% LDL-C reduction provides prognostic benefit independent of attaining an absolute LDL-C goal in patients with ischemic stroke. METHODS: This retrospective cohort study included patients admitted for acute ischemic stroke (2014-2022) using the Korean National Health Insurance Database in South Korea. LDL-C status over time was derived from serial national health examinations following the index stroke. Patients were categorized into 4 groups according to attainment of absolute (<70 mg/dL) and relative (≥50% reduction from baseline) LDL-C goals. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause death, analyzed using time-varying Cox regression. RESULTS: Among 89,414 patients, 136,427 poststroke LDL-C measurements were analyzed over a mean follow-up of 5.72 ± 2.40 years. Throughout the follow-up period, the proportion of patients achieving a ≥50% LDL-C reduction from baseline remained at approximately 30%. Using the optimal group (achieving both <70 mg/dL and ≥50% reduction) as the reference, the risk of the primary outcome was significantly higher in groups failing to achieve a ≥50% reduction, regardless of attainment of the absolute LDL-C level (<70 mg/dL): adjusted hazard ratio [95% CI] 1.12 [1.06-1.18] for the <70 mg/dL and <50% reduction group and 1.28 [1.23-1.34] for the ≥70 mg/dL and <50% reduction group. Results were consistent across subgroups stratified by sex, age, baseline LDL-C level, and the presence of presumed cardioembolic source. DISCUSSION: Achieving a ≥50% reduction in LDL-C from baseline was independently associated with a lower risk of secondary cardiovascular events. A substantial proportion of patients with ischemic stroke fail to achieve optimal LDL-C reduction; thus, more intensive and multifaceted lipid-lowering strategies focusing on both absolute and relative LDL-C reduction may lead to improved long-term outcomes.