Effect of adding PCSK9 inhibitors to lipid-lowering interventions on arterial stiffness: A systematic review and meta-analysis

IF 4.4 3区医学 Q1 MEDICINE, GENERAL & INTERNAL

European Journal of Clinical Investigation Pub Date : 2024-06-21 DOI:10.1111/eci.14269

I. Cavero-Redondo, N. Moreno-Herraiz, A. Del Saz-Lara, I. Otero-Luis, J. I. Recio-Rodriguez, A. Saz-Lara

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Abstract

Background

Atherosclerosis, a leading cause of mortality, necessitates effective management of hypercholesterolemia, specifically elevated low-density lipoprotein cholesterol (LDL-C). The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has revolutionised lipid-lowering. PCSK9i demonstrates substantial LDL-C reduction and cardiovascular benefits, particularly in statin-intolerant or nonresponsive individuals. However, the potential pleiotropic effects of PCSK9i, especially on arterial stiffness, remain a subject of investigation. This systematic review and meta-analysis seek to provide a nuanced understanding of the potential pleiotropic effects of PCSK9i, specifically on arterial health. The primary objective was to analyse the influence of PCSK9i on arterial stiffness, extending beyond traditional lipid-lowering metrics and contributing to a more comprehensive approach to cardiovascular risk reduction.

Methods

A systematic search was conducted across major databases, clinical trial registries and grey literature. Inclusion criteria comprised adults in prospective cohort studies undergoing PCSK9i augmentation in lipid-lowering therapy, with a focus on arterial stiffness measured by pulse wave velocity (PWv). Random-effects meta-analyses, sensitivity analyses and meta-regression models were employed to assess the pooled effect of adding PCSK9i to lipid-lowering interventions on arterial stiffness.

Results

Five studies (158 participants) met the inclusion criteria, demonstrating a significant reduction in PWv (mean difference: −2.61 m/s [95% CI: −3.70, −1.52]; ES: −1.62 [95% CI: −2.53, −.71]) upon adding PCSK9i to lipid-lowering interventions. Subgroup analysis and meta-regression models suggested potential sex-based and baseline PWv-dependent variations, emphasising patient-specific characteristics.

Conclusion

The meta-analysis provides robust evidence that adding PCSK9i to lipid-lowering interventions significantly improves arterial stiffness, indicating broader vascular benefits beyond LDL-C reduction.

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在降脂干预中加入 PCSK9 抑制剂对动脉僵化的影响：系统回顾和荟萃分析

背景动脉粥样硬化是导致死亡的主要原因，因此必须有效控制高胆固醇血症，特别是升高的低密度脂蛋白胆固醇（LDL-C）。蛋白转换酶亚基酶/kexin 9 型抑制剂（PCSK9i）的出现彻底改变了降脂治疗。PCSK9i 可显著降低低密度脂蛋白胆固醇（LDL-C）并对心血管有益，尤其是对他汀类药物不耐受或无反应的患者。然而，PCSK9i 潜在的多生物效应，尤其是对动脉僵化的影响，仍是一个研究课题。本系统综述和荟萃分析旨在深入了解 PCSK9i 的潜在多效应，尤其是对动脉健康的影响。主要目的是分析 PCSK9i 对动脉僵化的影响，超越传统的降脂指标，为采用更全面的方法降低心血管风险做出贡献。纳入标准包括接受 PCSK9i 增强降脂治疗的前瞻性队列研究中的成人，重点关注通过脉搏波速度 (PWv) 测量的动脉僵化。采用随机效应荟萃分析、敏感性分析和荟萃回归模型来评估在降脂干预措施中添加 PCSK9i 对动脉僵化的总体影响。结果5项研究（158名参与者）符合纳入标准，显示脉搏波速度显著降低（平均差异为-2.61 m/s [95%：平均差异：-2.61 m/s [95% CI：-3.70, -1.52]; ES：-ES：-1.62 [95% CI：-2.53, -.71]）。荟萃分析提供了强有力的证据表明，在降脂干预中加入 PCSK9i 能显著改善动脉僵化，这表明除了降低 LDL-C 外，还能为血管带来更广泛的益处。

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来源期刊

European Journal of Clinical Investigation 医学-医学：内科

CiteScore

9.50

自引率

3.60%

发文量

192

审稿时长

1 months

期刊介绍： EJCI considers any original contribution from the most sophisticated basic molecular sciences to applied clinical and translational research and evidence-based medicine across a broad range of subspecialties. The EJCI publishes reports of high-quality research that pertain to the genetic, molecular, cellular, or physiological basis of human biology and disease, as well as research that addresses prevalence, diagnosis, course, treatment, and prevention of disease. We are primarily interested in studies directly pertinent to humans, but submission of robust in vitro and animal work is also encouraged. Interdisciplinary work and research using innovative methods and combinations of laboratory, clinical, and epidemiological methodologies and techniques is of great interest to the journal. Several categories of manuscripts (for detailed description see below) are considered: editorials, original articles (also including randomized clinical trials, systematic reviews and meta-analyses), reviews (narrative reviews), opinion articles (including debates, perspectives and commentaries); and letters to the Editor.