Beschreibung:
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<jats:title>Background:</jats:title>
<jats:p>Impaired endothelial function predicts cardiovascular events. The aim of this study was to analyse the effect of evolocumab on endothelial function in patients with cardiovascular disease and on obligatory statin therapy.</jats:p>
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<jats:title>Methods:</jats:title>
<jats:p>This was a prospective, double-blinded, randomized, controlled, single center study (NCT03626831) including patients with cardiovascular disease (diagnosis of coronary artery disease, non-hemorrhagic stroke, transient ischemic attack or symptomatic peripheral artery disease) and treated with statins, similar to the inclusion criteria of the FOURIER study. Patients were consecutively randomized (1:1) to either evolocumab treatment (420 mg was administrated in monthly intervals, twice during the study) 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; Unex Co., Nagoya, Japan). Endothelial function parameter such as flow-mediated vasodilation (FMD; vasodilator responsiveness), low flow-mediated vasocontriction (L-FMC; vasoconstrictor responsiveness) and vasoactive range (VAR; total vasomotor responsiveness) were measured.</jats:p>
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<jats:title>Results:</jats:title>
<jats:p>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. 83.5% of the study population was known to have coronary artery disease. 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).</jats:p>
<jats:p>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. No serious adverse event related to study medication occurred during the study.</jats:p>
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<jats:title>Conclusion:</jats:title>
<jats:p>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.</jats:p>
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