Kuang Jia, Hao Lei, Zhang Meibiao, Yang Zhao
Department of Neurology The Affiliated Yongchuan Hospital of Chongqing Medical University Chongqing China.
Department of Neurology The First Affiliated Hospital of Chongqing Medical University Chongqing China.
MedComm (2020). 2025 Nov 2;6(11):e70451. doi: 10.1002/mco2.70451. eCollection 2025 Nov.
Ischemic stroke remains a leading cause of global disability and death. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have emerged as potent lipid-lowering agents with expanding therapeutic potential. Beyond robust low-density lipoprotein cholesterol reduction, accumulating evidence suggests these drugs may confer benefits in ischemic stroke prevention and management. However, challenges regarding accessibility, real-world efficacy, and integration into combination therapies persist, necessitating a comprehensive evidence synthesis. This review systematically consolidates the molecular mechanisms of PCSK9 inhibition and classifies current inhibitors. We delineate recent preclinical advances underscoring their neuroprotective and vasculoprotective effects, alongside critical findings from major clinical trials. These developments highlight promising avenues for both secondary prevention and acute-phase treatment strategies. Collectively, this synthesis establishes a foundational framework for positioning PCSK9 inhibitors as transformative agents in stroke therapeutics and paves the way for precision neurovascular medicine.
缺血性中风仍然是全球残疾和死亡的主要原因。前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）抑制剂已成为强效降脂药物，治疗潜力不断扩大。除了能有效降低低密度脂蛋白胆固醇外，越来越多的证据表明，这些药物在缺血性中风的预防和治疗中可能具有益处。然而，在可及性、实际疗效以及与联合疗法的整合方面仍存在挑战，因此需要进行全面的证据综合分析。本综述系统地整合了PCSK9抑制的分子机制，并对目前的抑制剂进行了分类。我们阐述了近期临床前研究的进展，突出了它们的神经保护和血管保护作用，以及主要临床试验的关键结果。这些进展为二级预防和急性期治疗策略都开辟了有前景的途径。总体而言，这一综合分析为将PCSK9抑制剂定位为中风治疗中的变革性药物建立了基础框架，并为精准神经血管医学铺平了道路。
