Effects of Evolocumab on Vitamin E and Steroid Hormone Levels: Results From the 52-Week, Phase 3, Double-blind, Randomized, Placebo-Controlled DESCARTES Study
Rationale: Vitamin E transport and steroidogenesis are closely associated with low-density lipoproteins (LDL) metabolism, and evolocumab can lower LDL-cholesterol (LDL-C) to low levels.
Objective: To determine the effects of evolocumab on vitamin E and steroid hormone levels.
Methods and Results: 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 (ACTH), 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 (RCM) 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 RCM vitamin E levels did not change. Cortisol in evolocumab-treated patients increased slightly from baseline to week 52, but ACTH and the cortisol/ACTH ratio did not change. No patient had a cortisol/ACTH 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 mmol/L and <0.6 mmol/L.
Conclusions: 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.
Clinical Trial Registration: NCT01516879.
- vitamin E
- steroid hormones
- low-density lipoprotein
- low-density lipoprotein cholesterol
- Received June 25, 2015.
- Revision received July 15, 2015.
- Accepted July 30, 2015.