Decline in LDL-C control in patients with dyslipidemia treated with PCSK9-inhibitors: The role of obesity in LDL-C target achievement.

IF 4.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of clinical lipidology Pub Date : 2025-06-25 DOI:10.1016/j.jacl.2025.06.018

Elena Formisano, Andrea Vignati, Almina Bertolini, Valeria Maria Barreto Spandonari, Michele Tafuro, Andrea Pasta, Samir Giuseppe Sukkar, Livia Pisciotta

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引用次数: 0

Abstract

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-Is: alirocumab and evolocumab) have improved dyslipidemia management in patients with high cardiovascular risk. However, some patients fail to reach low-density lipoprotein cholesterol (LDL-C) targets.

Objective: To evaluate factors influencing PCSK9-I therapy effectiveness.

Methods: A retrospective study (2018-2023) analyzed adults treated with a PCSK9-I for at least 6 months with heterozygous familial hypercholesterolemia (He-FH) in primary prevention, dyslipidemia in secondary prevention, or diabetes with associated complications. Clinical, anthropometric data and lipid profiles were collected at baseline and after 6, 12, 24, and 36 months. The primary outcome was LDL-C target achievement according to European Society of Cardiology/European Atherosclerosis Society guidelines.

Results: Among 180 patients, approximately 45% achieved the LDL-C target. Patients with overweight and obesity showed significantly lower LDL-C reductions compared to normal-weight patients. Those reductions for overweight patients were 47.8%, 50.0%, and 44.0%, and for obese patients were 25.6%, 29.4%, and 28.6%, whereas normal-weight patients achieved reductions of 54.5% (P = .021), 62.5% (P = .024), and 65.4% (P = .024), respectively. Multivariate analysis confirmed these findings (odds ratio [OR]: 0.18, 95% CI, 0.06-0.53, P = .002) and highlighted that He-FH was associated with lower likelihood of achieving LDL-C targets (OR: 0.35, 95% CI, 0.15-0.82, P = .015). Conversely, patients with coronary artery disease (CAD) were more likely to reach LDL-C targets (OR: 4.54, 95% CI, 1.98-10.41, P < .0001). Concomitant oral lipid-lowering therapy was linked to a higher probability of achieving LDL-C targets compared to PCSK9-I monotherapy (OR: 14.5, 95% CI 2.26-92.9, P = .005).

Conclusion: Overweight, He-FH, CAD, and concomitant oral lipid-lowering therapy could influence the achievement of LDL-C target in patients treated with PCSK9-Is.

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使用pcsk9抑制剂治疗的血脂异常患者LDL-C控制下降：肥胖在LDL-C目标实现中的作用

背景：Proprotein convertase subtilisin/ keexin 9型抑制剂（PCSK9-Is: alirocumab和evolocumab）改善了心血管高危患者的血脂异常管理。然而，一些患者未能达到低密度脂蛋白胆固醇（LDL-C）的目标。目的：评价影响PCSK9-I治疗效果的因素。方法：一项回顾性研究（2018-2023）分析了接受PCSK9-I治疗至少6个月的成人，这些成年人患有杂合子家族性高胆固醇血症（He-FH）一级预防，血脂异常二级预防或糖尿病伴相关并发症。在基线和6、12、24和36个月后收集临床、人体测量数据和脂质谱。根据欧洲心脏病学会/欧洲动脉粥样硬化学会指南，主要结局是LDL-C目标达到。结果：180例患者中，约45%达到LDL-C目标。与体重正常的患者相比，超重和肥胖患者的LDL-C下降明显更低。超重患者的减少率分别为47.8%、50.0%和44.0%，肥胖患者的减少率分别为25.6%、29.4%和28.6%，而正常体重患者的减少率分别为54.5% （P = 0.021）、62.5% （P = 0.024）和65.4% （P = 0.024）。多因素分析证实了这些发现（比值比[OR]: 0.18, 95% CI, 0.06-0.53, P = 0.002），并强调He-FH与低LDL-C目标实现可能性相关（OR: 0.35, 95% CI, 0.15-0.82, P = 0.015）。相反，冠状动脉疾病（CAD）患者更容易达到LDL-C目标（OR: 4.54, 95% CI, 1.98-10.41, P < 0.0001）。与PCSK9-I单药治疗相比，联合口服降脂治疗与实现LDL-C目标的可能性更高（OR: 14.5, 95% CI 2.26-92.9, P = 0.005）。结论：超重、He-FH、CAD及合并口服降脂治疗可影响PCSK9-Is患者LDL-C达标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of clinical lipidology 医学-药学

CiteScore

7.00

自引率

6.80%

发文量

209

审稿时长

49 days

期刊介绍： Because the scope of clinical lipidology is broad, the topics addressed by the Journal are equally diverse. Typical articles explore lipidology as it is practiced in the treatment setting, recent developments in pharmacological research, reports of treatment and trials, case studies, the impact of lifestyle modification, and similar academic material of interest to the practitioner. Sections of Journal of clinical lipidology will address pioneering studies and the clinicians who conduct them, case studies, ethical standards and conduct, professional guidance such as ATP and NCEP, editorial commentary, letters from readers, National Lipid Association (NLA) news and upcoming event information, as well as abstracts from the NLA annual scientific sessions and the scientific forums held by its chapters, when appropriate.