Pęczek Piotr, Leśniewski Mateusz, Mazurek Tomasz, Szarpak Lukasz, Filipiak Krzysztof J, Gąsecka Aleksandra
1st Chair and Department of Cardiology, Medical University of Warsaw, 00-927 Warsaw, Poland.
Department of Research Outcomes, Maria Sklodowska-Curie Medical Academy in Warsaw, 03-411 Warsaw, Poland.
Life (Basel). 2021 May 23;11(6):466. doi: 10.3390/life11060466.
Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel group of hypolipidemic drugs that are recommended particularly for high-risk hypercholesterolemia patients, including those with primary hypercholesterolemia (PH), where lifelong exposure to high low-density lipoprotein (LDL) cholesterol levels results in an elevated risk of atherosclerosis at an early age. The onset and progression of atherosclerosis is significantly influenced by activated platelets. Oxidized LDL influences platelet activation by interacting with their surface receptors and remodeling the composition of their cell membrane. This results in platelet aggregation, endothelial cell activation, promotion of inflammation and oxidative stress, and acceleration of lipid accumulation in atherosclerotic plaques. PCSK9 inhibitors reduce platelet activation by both significantly lowering LDL levels and reducing the LDL receptor-mediated activation of platelets by PCSK9. They also work synergistically with other hypolipidemic and antithrombotic drugs, including statins, ezetimibe, acetylsalicylic acid, clopidogrel, and ticagrelor, which enhances their antiplatelet and LDL-lowering effects. In this review, we summarize the currently available evidence on platelet hyperreactivity in PH, the effects of PCSK9 inhibitors on platelets, and their synergism with other drugs used in PH therapy.
前蛋白转化酶枯草溶菌素9型（PCSK9）抑制剂是一类新型的降血脂药物，特别推荐用于高危高胆固醇血症患者，包括原发性高胆固醇血症（PH）患者，这些患者终身处于高低密度脂蛋白（LDL）胆固醇水平，会在早年导致动脉粥样硬化风险升高。动脉粥样硬化的发生和进展受到活化血小板的显著影响。氧化型LDL通过与其表面受体相互作用并重塑其细胞膜组成来影响血小板活化。这会导致血小板聚集、内皮细胞活化、促进炎症和氧化应激，并加速动脉粥样硬化斑块中的脂质积累。PCSK9抑制剂通过显著降低LDL水平以及减少PCSK9介导的LDL受体对血小板的活化来降低血小板活化。它们还与其他降血脂和抗血栓药物协同作用，包括他汀类药物、依泽替米贝、乙酰水杨酸、氯吡格雷和替卡格雷，从而增强其抗血小板和降低LDL的作用。在本综述中，我们总结了目前关于PH中血小板高反应性、PCSK9抑制剂对血小板的影响及其与PH治疗中使用的其他药物协同作用的现有证据。
