Key result
Adding PCSK9 inhibitors to lipid-lowering interventions significantly reduced arterial stiffness measured by pulse wave velocity (mean difference -2.61 m/s; 95% CI -3.70 to -1.52).
Why the study?
Although PCSK9 inhibitors provide substantial LDL-C reduction and cardiovascular benefits, their potential pleiotropic effects, particularly on arterial stiffness, remain a subject of investigation.
Does adding PCSK9 inhibitors to lipid-lowering interventions reduce arterial stiffness in adults?
Meta-Analysis (n=158)
Does adding PCSK9 inhibitors to lipid-lowering interventions reduce arterial stiffness in adults?
Mean Difference: -2.61 (95% CI -3.7–-1.52)
Adding PCSK9 inhibitors to lipid-lowering therapy significantly reduces arterial stiffness as measured by pulse wave velocity, suggesting pleiotropic vascular benefits beyond LDL-C reduction.
Supports adjunctive PCSK9i for vascular health beyond LDL-C reduction; extends meta-analytic evidence on pleiotropic effects in hypercholesterolemia.
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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Cavero‐Redondo et al. (2024) conducted a meta-analysis in hypercholesterolemia (n=158). PCSK9 inhibitors vs. lipid-lowering interventions without PCSK9i was evaluated on arterial stiffness measured by pulse wave velocity (PWv) (MD -2.61, 95% CI -3.70 to -1.52). Adding PCSK9 inhibitors to lipid-lowering interventions significantly reduced arterial stiffness measured by pulse wave velocity (mean difference -2.61 m/s; 95% CI -3.70 to -1.52).
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