PCSK-9-inhibitor therapy improves endothelial function in patients with coronary artery disease

Abstract Objective Impaired endothelial function is a key mediator of coronary artery disease and predicts cardiovascular events. This analysis reports the effect of evolocumab on endothelial function in high-risk patients with coronary artery disease, who participated in a prospective, double-blinded, randomized, controlled clinical trial. Design and method: The analysis includes 78 male and female patients aged between 40 and 80 years with diagnosis of coronary artery disease as evidenced by acute coronary syndrome, myocardial infarction, coronary stent implantation or coronary stenosis ≥ 50% by coronary angiography in stable condition. Patients had to have a fasting LDL-C level of at least 70 mg per deciliter or a non-high-density lipoprotein cholesterol (HDL-C) level of at least 100 mg per deciliter while on a high-intensity statin therapy. All patients were consecutively randomized 1:1 on either evolocumab treatment or placebo. Endothelial function was examined by a semi-automatic high-resolution ultrasound system (UNEX EF 18G) at baseline, and after 8 weeks of treatment. Parameters of endothelial function were flow-mediated vasodilation (FMD), low flow-mediated vasoconstriction (L-FMC) and vasoactive range (VAR). Results Patients had a mean age of 66.5 ± 7.4 years and a mean LDL-cholesterol of 101 ± 17.2 mg/dl. 8-weeks treatment with evolocumab reduced LDL-cholesterol to a mean of 47.5 ± 12.6 mg/dl (p < 0.001). No significant changes were seen in the placebo group (LDL-cholesterol after 8-weeks treatment: 99.9 ± 22.5 mg/dl (p = 0.748). The change in VAR from baseline to week 8 was significantly different with evolocumab compared to placebo (p = 0.047) (Figure 1). No significant changes have been found in FMD and L-FMC after 8 weeks of treatment with evolocumab (Figure 1). Conclusion Our data indicate that endothelial function improves with evolocumab treatment in high-risk patients with coronary artery disease on statin therapy. Thus, our results add mechanistic explanation to the lower incidence of the cardiovascular composite endpoint demonstrated in the FOURIER study.Figure 1