Lipid-lowering therapy for secondary stroke prevention beyond statin monotherapy: a mechanism-informed approach across drug classes and stroke subtypes

INTRODUCTION: Intensive lipid lowering is crucial for secondary prevention of ischemic stroke, but achieving low-density lipoprotein cholesterol (LDL-C) targets and selecting additional agents beyond statins are challenging. Stroke mechanisms vary in their contribution to atherosclerosis, so the benefits, risks, and treatment burdens of aggressive LDL-C reduction may differ among phenotypes. AREAS COVERED: The authors searched PubMed/MEDLINE and Google Scholar for studies published through September 2026 on lipid-lowering therapy after ischemic stroke or transient ischemic attack. The authors prioritize randomized trials, subgroup analyses, stroke-specific observational studies, meta-analyses, and major guidelines or consensus documents and assess the evidence by study design, stroke phenotype, and whether outcomes were clinical events or surrogate measures, including LDL-C target attainment and plaque imaging. EXPERT OPINION: Future lipid management after ischemic stroke could improve by combining stroke phenotype and atherosclerotic burden with established cardiovascular risk and LDL-C targets. Early combination therapy may help plaque-driven stroke patients reach targets, but its effect on recurrence is unproven. Evidence is limited by few stroke-specific trials, reliance on surrogate endpoints, and barriers including advanced imaging and biologic reimbursement. Phenotype-stratified trials should test whether mechanism-informed care improves outcomes and cost-effectiveness beyond guidelines.