PCSK-9-inhibitor Therapy Improves Endothelial Function in High-risk Patients with Cardiovascular Disease

Overview

Journal Clin Res Cardiol

Specialty Cardiology & Vascular Diseases

Date 2024 Nov 20

PMID 39565386

Authors

Dennis Kannenkeril

Agnes Bosch

Julie Kolwelter

Kristina Striepe

Laura Berner

Robert Pietschner

Christian Ott

Mario Schiffer

Stephan Achenbach

Roland E Schmieder

Affiliations

Soon will be listed here.

Abstract

Background: Impaired endothelial function predicts cardiovascular events. The aim of this study was to analyze the effect of evolocumab on endothelial function in patients with cardiovascular disease.

Methods: This was a prospective, double-blinded, randomized, controlled, single center study including patients with cardiovascular disease and treated with statins. Patients were consecutively randomized (1:1) to either evolocumab treatment or placebo. All patients underwent examination of endothelial function at baseline, and after 1, 4 and 8 weeks of treatment by a semi-automatic high-resolution ultrasound system (UNEX EF 18G). Parameters of endothelial function were flow-mediated vasodilation (FMD), low flow-mediated vasoconstriction (L-FMC) and vasoactive range (VAR).

Results: Hundred three patients with a mean age of 66.2 ± 7.7 years and a mean LDL-cholesterol of 98 ± 19.1 mg/dl completed the study. The change in VAR from baseline to week 8 was significantly different with evolocumab compared to placebo (p = 0.045). Moreover, VAR increased after 8 weeks of treatment with evolocumab compared to baseline (p = 0.034). No change has been noticed in FMD and L-FMC after 8 weeks of treatment with evolocumab. In subgroup analyses, VAR improved in patients with age ≤ 67 years, lower systolic blood pressure (≤ 125 mmHg) and higher baseline LDL-cholesterol (> 95 mg/dl), (p = 0.006, p = 0.049 and p = 0.042, respectively) after 8 weeks of evolocumab treatment. No serious adverse event related to study medication occurred during the study.

Conclusion: Our data indicate that endothelial function improved with evolocumab treatment in high-risk patients on statin therapy with preexisting cardiovascular disease. Our results contribute to the mechanistic explanation why lower incidence of the cardiovascular composite endpoint has been demonstrated in the FOURIER study.

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