UO Lipoapheresis and Center for Inherited Dyslipidemias, Fondazione Toscana Gabriele Monasterio, Pisa.
UOC Farmacia Ospedaliera, Fondazione Toscana Gabriele Monasterio, Massa, Italy.
J Cardiovasc Med (Hagerstown). 2023 Nov 1;24(11):808-814. doi: 10.2459/JCM.0000000000001546. Epub 2023 Sep 29.
Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a breakthrough in the treatment of hypercholesterolemia. The aim of this study was to perform a multicentre prospective analysis on the effects of PCSK9i since their distribution in Italy.
During the study period (July 2017 to February 2022) 246 patients (mean age 61 ± 11 years, male 73%) who were evolocumab (142/246) or alirocumab (104/246) new users were enrolled in the CERTI (Costo Efficacia Regione Toscana Inibitori PCSK9) study. Lipid value, adverse events (AEs), major cardiovascular events (MACEs) and intima-media thickness were analysed.
PCSK9i therapy allowed a significant improvement in patients' lipid profile [total cholesterol -35%, P < 0.001; triglycerides -9%, P < 0.05; low-density lipoprotein (LDL) cholesterol -51%, P < 0.001; Lp(a) levels -4%, P < 0.05], maintained during the follow-up. No significant variations in intima-media thickness were observed. In the subgroup of patients with more than 1 year of PCSK9i therapy (165/246 patients) we highlighted: a 66% reduction in MACEs compared with the year before recruitment; a progressive increase in MACEs during the follow-up (MACEs event/rate at first year 0.08 vs. MACEs event/rate at year 5: 0.47); a patients cluster with late MACEs older, with higher prevalence of hypertension, smoking habit and peripheral vascular disease. During the follow-up, we recorded AEs in 31% of patients, which mainly resulted in reduction/discontinuation of lipid-lowering therapy for 50 patients or in discontinuation/shift of PCSK9i (respectively 8 and 6 cases).
Our data agree with the large evidence on the effectiveness/tolerability of PCSK9i therapy; however, although PCSK9i represents a good cholesterol-lowering therapeutic option, our study shows a progressive increase in MACEs during the late follow-up that deserve further research.
前蛋白转化酶枯草溶菌素 9 抑制剂（PCSK9i）在治疗高胆固醇血症方面是一项突破。本研究的目的是对意大利分布的 PCSK9i 进行多中心前瞻性分析。
在研究期间（2017 年 7 月至 2022 年 2 月），共纳入 246 名新使用依洛尤单抗（142/246）或阿利西尤单抗（104/246）的患者，平均年龄 61±11 岁，男性 73%。分析血脂值、不良事件（AE）、主要心血管事件（MACE）和内膜中层厚度。
PCSK9i 治疗可显著改善患者的血脂谱[总胆固醇-35%，P<0.001；甘油三酯-9%，P<0.05；低密度脂蛋白胆固醇-51%，P<0.001；脂蛋白（a）水平-4%，P<0.05]，且在随访期间保持不变。内膜中层厚度无明显变化。在 PCSK9i 治疗时间超过 1 年的患者亚组（246 例患者中的 165 例）中，我们发现：与招募前一年相比，MACE 减少了 66%；随访期间 MACE 逐渐增加（第一年 MACE 事件/发生率为 0.08，第五年 MACE 事件/发生率为 0.47）；一个具有晚期 MACE 的患者聚类更年长，高血压、吸烟习惯和外周血管疾病的患病率更高。随访期间，31%的患者出现 AE，其中 50 例患者因降脂治疗减少/停止，6 例患者因 PCSK9i 减少/转移而停止/转移。
我们的数据与 PCSK9i 治疗有效性/耐受性的大量证据一致；然而，尽管 PCSK9i 是一种很好的降胆固醇治疗选择，但我们的研究表明，在晚期随访期间，MACE 逐渐增加，这需要进一步研究。
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