Therapy
Individualised, phenotype-guided dyslipidaemia management for stroke prevention, review covering Lp(a)-lowering agents (Int J Stroke 2026)
Original title: Dyslipidemia management in stroke prevention: An individualized approach
Review proposing a phenotype-guided, individualised framework for dyslipidaemia management across stroke subtypes, since dyslipidaemia accounts for more than one-fifth of ischaemic strokes worldwide. ApoB-containing lipoproteins, including Lp(a), better reflect atherogenic burden than LDL-C alone and are increasingly used for stroke risk stratification. High-intensity statins remain first-line therapy; ezetimibe and PCSK9 inhibitors provide bleeding-neutral options for statin intolerance; inclisiran and bempedoic acid broaden choices pending stroke-specific outcome data; and icosapent ethyl reduces ischaemic stroke risk via triglyceride lowering. Lp(a)-lowering agents pelacarsen, olpasiran and lepodisiran are under active evaluation for residual risk. In intracerebral haemorrhage, particularly lobar haemorrhage or suspected cerebral amyloid angiopathy, lipid-lowering intensity and thresholds remain uncertain and require individualised weighting of ischaemic against haemorrhagic risk.
Original abstract
Dyslipidemia remains a major, modifiable determinant of global stroke burden, accounting for more than one-fifth of ischemic strokes (IS) worldwide. Recent evidence has shifted emphasis from conventional lipid fractions to apolipoprotein B (ApoB)-containing lipoproteins, including lipoprotein(a) [Lp(a)], which more accurately reflect atherogenic particle burden than low-density lipoprotein cholesterol (LDL-C) alone and are increasingly used for stroke risk stratification. While the principle "the faster and the lower, the better" underpins dyslipidemia management, evidence-based, subtype-specific lipid strategies in stroke remain limited. Intensive LDL-C reduction significantly lowers recurrent IS risk; however, uniform lipid targets are often applied without accounting for stroke etiology. High-intensity statins remain first-line therapy, with pleiotropic benefits extending beyond LDL-C reduction. For statin intolerance or suboptimal response, ezetimibe and PCSK9 inhibitors provide potent, bleeding-neutral LDL-C lowering. Inclisiran and bempedoic acid broaden therapeutic options, although stroke-specific efficacy data are still pending. Lp(a)-lowering agents, including pelacarsen, olpasiran, and lepodisiran, are under active evaluation and may address residual cardiovascular risk. For triglyceride lowering, recent randomized evidence supports icosapent ethyl for reducing IS risk. In intracerebral hemorrhage (ICH), the optimal intensity and thresholds of lipid lowering remain uncertain, warranting individualized weighting of ischemic against hemorrhagic risk, particularly in patients with lobar ICH or suspected cerebral amyloid angiopathy (CAA). In such cases, hydrophilic statins, ezetimibe, or PCSK9 inhibitors may represent reasonable options. This review synthesizes current evidence and proposes a phenotype-guided, individualized framework for dyslipidemia management across stroke subtypes. Moving beyond uniform targets toward etiologic and genetically informed lipid modulation may improve post-stroke outcomes and refine individualized stroke prevention.
olpasiranpelacarsenstroketherapy
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.