PCSK9抑制剂的心血管保护作用及其在心衰治疗中的研究进展

Cardiovascular Protective Effects of PCSK9 Inhibitors and Research Progress in Their Application for Heart Failure Treatment

摘要: 动脉粥样硬化性心血管疾病(ASCVD)与心力衰竭(HF)疾病负担沉重，而他汀类药物存在局限性。前蛋白转化酶枯草溶菌素9 (PCSK9)抑制剂是一种新型强效降脂药，能显著降低低密度脂蛋白胆固醇(LDL-C)水平，减少主要不良心血管事件(MACE)发生，且安全性良好。本文综述了PCSK9抑制剂在ASCVD和心衰中的研究进展。尽管其通过稳定斑块及减少心肌梗死的发生来间接预防心衰，但对于已经发生心衰的患者临床获益尚无定论，被称为“治疗悖论”。但PCSK9抑制剂可能通过抑制心肌细胞死亡、抗炎和抗纤维化等降脂机制发挥直接心脏保护作用。未来研究需聚焦于PCSK9抑制剂在不同心衰表型中的疗效，并探索PCSK9作为生物标志物的价值，以明确其在心衰治疗中的地位。

Abstract: Atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) represent major burdens in cardiovascular disease, while statins have their limitations. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a novel class of potent lipid-lowering agents that significantly reduce low-density lipoprotein cholesterol (LDL-C) levels, decrease major adverse cardiovascular events (MACE), and exhibit a favorable safety profile. This review summarizes recent advances in the research of PCSK9 inhibitors in ASCVD and HF. Although they indirectly prevent HF by stabilizing plaques and reducing the incidence of myocardial infarction, their clinical benefits for patients with established HF remain inconclusive, a phenomenon referred to as the “treatment paradox.” However, PCSK9 inhibitors may exert direct cardioprotective effects through lipid-independent mechanisms such as inhibiting cardiomyocyte death, anti-inflammatory actions, and anti-fibrotic effects. Future studies should focus on their efficacy across different HF phenotypes and explore the value of PCSK9 as a biomarker to clarify its role in HF treatment.