Effect of evolocumab on fasting and post fat load lipids and lipoproteins in familial dysbetalipoproteinemia

Britt E. Heidemann, Charlotte Koopal, Jeanine E. Roeters van Lennep, Erik S.G. Stroes, Niels P. Riksen, Monique T. Mulder, Leonie C.van Vark – van der Zee, Dee M. Blackhurst, A. David Marais, Frank L.J. Visseren*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
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Abstract

BACKGROUND: Familial dysbetalipoproteinemia (FD) is the second most common monogenic lipid disorder (prevalence 1 in 850-3500), characterized by postprandial remnant accumulation and associated with increased cardiovascular disease (CVD) risk. Many FD patients do not achieve non-HDL-C treatment goals, indicating the need for additional lipid-lowering treatment options. OBJECTIVES: To evaluate the effect of the PCSK9 monoclonal antibody evolocumab added to standard lipid-lowering therapy on fasting and post fat load lipids and lipoproteins in patients with FD. METHODS: A randomized placebo-controlled double-blind crossover trial comparing evolocumab (140 mg subcutaneous every 2 weeks) with placebo during two 12-week treatment periods. At the start and end of each treatment period patients received an oral fat load. The primary endpoint was the 8-hour post fat load non-HDL-C area under the curve (AUC). Secondary endpoints included fasting and post fat load lipids and lipoproteins. RESULTS: In total, 28 patients completed the study. Mean age was 62±9 years and 93% had an Ɛ2Ɛ2 genotype. Evolocumab reduced the 8-hour post fat load non-HDL-C AUC with 49% (95%CI 42-55) and apolipoprotein B (apoB) AUC with 47% (95%CI 41-53). Other fasting and absolute post fat load lipids and lipoproteins including triglycerides and remnant-cholesterol were also significantly reduced by evolocumab. However, evolocumab did not have significant effects on the rise above fasting levels that occurred after consumption of the oral fat load. CONCLUSIONS: Evolocumab added to standard lipid-lowering therapy significantly reduced fasting and absolute post fat load concentrations of non-HDL-C, apoB and other atherogenic lipids and lipoproteins in FD patients. The clinically significant decrease in lipids and lipoproteins can be expected to translate into a reduction in CVD risk in these high-risk patients.

Original languageEnglish
Pages (from-to)112-123
Number of pages12
JournalJournal of Clinical Lipidology
Volume17
Issue number1
Early online date28 Oct 2022
DOIs
Publication statusPublished - 1 Jan 2023

Bibliographical note

Funding Information:
This project was funded by Amgen for an investigator-initiated research project. The University Medical Center Utrecht was the sponsor of the study. The financial funder had no role in the design, collection of the data, conduct of the analyses or reporting of the study results. The authors gratefully acknowledge the contribution of the patients and the study teams at the four Academic study sites. - University Medical Center Utrecht: C.A.M. Joosten and I.P. Klaassen. - Erasmus Medical Center Rotterdam: K.A. Steward. - Amsterdam University Medical Center: P.J.M. Zweers, drs. A.J. Cupido, drs. A.C. Fenneman. - Radboud University Medical Center Nijmegen: A. Rasing-Hoogveld, dr. E. Abbink. - Independent study physician: dr. J. Westerink. - Central laboratory: M. Wesseling, dr. M. ten Berg, dr. I. Höfer. - Central pharmacy: dr. A. Lalmohamed.

Publisher Copyright:
© 2022

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