Optimal LDL-C Levels for Ischemic Stroke Prevention: A Neurologist's Perspective

Low-density lipoprotein cholesterol (LDL-C) lowering is a central therapeutic strategy in atherosclerotic cardiovascular disease (ASCVD) and is also important for ischemic stroke. As outcome-driven evidence has accumulated, lipid management guidelines have progressively adopted more stringent LDL-C targets. Landmark trials of statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors have shown consistent cardiovascular benefit across progressively lower achieved LDL-C levels in ASCVD. In the stroke field, randomized controlled trials, including Stroke Prevention by Aggressive Reduction in Cholesterol Levels and Treat Stroke to Target, have provided stroke-specific evidence supporting intensive LDL-C lowering for secondary prevention, particularly in patients with atherosclerotic stroke. Beyond its established role in long-term secondary prevention, emerging evidence suggests that intensive LDL-C lowering may also affect the early clinical course after ischemic stroke. Nevertheless, important knowledge gaps remain. Ischemic stroke is a heterogeneous disease with diverse etiologic mechanisms, including nonatherosclerotic subtypes such as small vessel occlusion and cardioembolism. Because evidence-based LDL-C targets for these populations remain poorly defined, current guidelines focus mainly on atherosclerotic stroke, leaving uncertainty regarding optimal lipid management in nonatherosclerotic stroke subtypes. Ongoing large-scale clinical trials specifically targeting these populations are expected to address this gap and to inform more tailored lipid-lowering strategies in stroke care. This review summarizes current evidence on LDL-C targets and lipid-lowering therapy in ischemic stroke and considers the implications for clinical practice and future research.