Effects of Evolocumab on Vitamin E and Steroid Hormone Levels. Issue 8 (25th September 2015)

• Record Type: Journal Article
• Authors: Blom, Dirk J.; Djedjos, C. Stephen; Monsalvo, Maria Laura; Bridges, Ian; Wasserman, Scott M.; Scott, Rob; Roth, Eli
• Is Part Of: Circulation research. Volume 117:Issue 8(2015)
• Publication Date: 2015-09-25
• Subjects: Cardiovascular system -- Periodicals; Blood -- Circulation -- Periodicals; Blood Circulation; Cardiovascular System; Vascular Diseases; Sang -- Circulation -- Périodiques; Appareil cardiovasculaire -- Périodiques; 612.1
• DOI: 10.1161/CIRCRESAHA.115.307071
• Languages: English
• ISSNs: 0009-7330

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title> <underline>Rationale</underline>:</title> <p>Vitamin E transport and steroidogenesis are closely associated with low-density lipoproteins (LDLs) metabolism, and evolocumab can lower LDL cholesterol (LDL-C) to low levels.</p> </sec> <sec> <title> <underline>Objective:</underline> </title> <p>To determine the effects of evolocumab on vitamin E and steroid hormone levels.</p> </sec> <sec> <title> <underline>Methods and Results:</underline> </title> <p>After titration of background lipid-lowering therapy per cardiovascular risk, 901 patients with an LDL-C ≥2.0 mmol/L were randomized to 52 weeks of monthly, subcutaneous evolocumab, or placebo. Vitamin E, cortisol, adrenocorticotropic hormone, and gonadal hormones were analyzed at baseline and week 52. In a substudy (n=100), vitamin E levels were also measured in serum, LDL, high-density lipoprotein, and red blood cell membranes at baseline and week 52. Absolute vitamin E decreased in evolocumab-treated patients from baseline to week 52 by 16% but increased by 19% when normalized for cholesterol. In the substudy, vitamin E level changes from baseline to week 52 mirrored the changes in the lipid fraction, and red blood cell membrane vitamin E levels did not change. Cortisol in evolocumab-treated patients increased slightly from baseline to week 52, but adrenocorticotropic hormone and the cortisol:adrenocorticotropic hormone ratio did not change. No patient had a cortisol:adrenocorticotropic hormone ratio <3.0 (nmol/pmol). Among evolocumab-treated patients, gonadal hormones did not change from baseline to week 52. Vitamin E and steroid changes were consistent across subgroups by minimum postbaseline LDL-C <0.4 and <0.6 mmol/L.</p> </sec> <sec> <title> <underline>Conclusions:</underline> </title> <p>As expected, vitamin E levels changed similarly to lipids among patients treated for 52 weeks with evolocumab. No adverse effects were observed in steroid or gonadal hormones, even at very low LDL-C levels.</p> </sec> <sec> <title> <underline>Clinical Trial Registration:</underline> </title> <p>URL: <ext-link ext-link-type="uri" xlink:href="http://www.clinicaltrials.gov" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.clinicaltrials.gov</ext-link>. Unique identifier: NCT01516879.</p> </sec> </abstract>