Abstract 13958: Evolocumab Alters Vascular Function in Patients With Cardiovascular Disease

Background: The aim of this study was to analyze the effect of evolocumab on vascular function and structure in patients with cardiovascular disease. Methods: This was a prospective, double-blinded, randomized, controlled study (NCT03626831) including patients with cardiovascular disease and treated with statins. Patients were consecutively randomized (1:1) to either evolocumab treatment (420mg was administrated twice during the study) or placebo. All patients underwent vascular examination at baseline, and after 1, 4 and 8 weeks of treatment by the SphygmoCor XCEL System (pulse wave analysis) and the UNEX EF 18G system (endothelial function). Endothelial function parameter such as flow-mediated vasodilation (FMD), low flow-mediated vasoconstriction (L-FMC) and vasoactive range (VAR) were measured. Moreover, pulse wave analysis parameters such as central systolic pressure, central pulse pressure, augmentation index, pulse wave velocity were measured. Results: 103 patients with a mean age of 66.2 (±7.7) years and a mean LDL-cholesterol of 98.2 (±19.1) mg/dl completed the study. LDL-cholesterol decreased significantly already after 1 week of treatment with evolocumab compared to baseline (-47.4 (±13.1) mg/dl). Endothelial function parameter (VAR) increased after 8 weeks of treatment with evolocumab compared to baseline (p=0.034), whereas there was no significant change at 1 and 4 weeks after treatment. Moreover, an improvement in VAR from baseline at week 8 was found with evolocumab compared to placebo (p=0.045). No change in the pulse wave analysis parameters were found with treatment. In a subgroup analysis, in patients with age ≤67 years, lower systolic blood pressure (≤125 mmHg) or higher baseline LDL-cholesterol (>95 mg/dl), significant evolocumab treatment effect was found in VAR improvement (p=0.006, p=0.049 and p=0.042, respectively) from baseline at week 8. Conclusion: Our data indicate that endothelial function could be improved with evolocumab treatment in high-risk patients with preexisting cardiovascular disease and on statin therapy. Our results contribute to the mechanistic explanation why lower incidence of the cardiovascular composite endpoint has been demonstrated in the FOURIER study.