Physicians' Academy for Cardiovascular Education

PCSK9i lowers lipids and lipoproteins in familial dysbetalipoproteinemia

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

Literature - Heidemann BE, Koopal C, Roeters van Lennep JE, et al. - - J Clin Lipidol. 2022 Oct 29;S1933-2874(22)00291-4 [Online ahead of print]. doi: 10.1016/j.jacl.2022.10.006

Introduction and methods

Background

Familial dysbetalipoproteinemia (FD), also known as “remnant removal disease”, is the second most common monogenic lipid disorder (prevalence 1 in 850–3500), after heterozygous familial hypercholesterolemia [1]. FD is characterized by accumulation of cholesterol-enriched remnants of triglyceride-rich lipoproteins, particularly during the postprandial phase, and is therefore associated with a very high risk of premature CVD [2-4].

As LDL and LDL-c levels are generally low or absent in patients with FD [5,6], treatment goals for this patient population are based on non–HDL-c levels. However, even with optimal therapy, 60% of FD patients do not achieve these goals [2]. Interestingly, in patients with T2DM, PCSK9i treatment resulted in a reduction of postprandial triglyceride-rich lipoproteins by 30%-40% [7-10].

Aim of the study

The study aim was to evaluate the effect of evolocumab added to standard lipid-lowering therapy on levels of fasting and post–fat load lipids and lipoproteins in FD patients.

Methods

The EVOLVE-FD (Effects of EVOLocumab VErsus placebo added to standard lipid-lowering therapy on fasting and post fat load lipids in patients with familial dysbetalipoproteinemia) trial was a randomized, investigator-initiated, placebo-controlled, double-blind, cross-over study conducted at 4 Dutch university medical centers. In this RCT, 28 patients with an FD genotype (confirmed by genotyping or isoelectric focusing) received evolocumab 140 mg subcutaneously every 2 weeks or placebo for 12 weeks. After an 8-week washout period, they were crossed over to the other treatment (evolocumab or placebo) for another 12 weeks.

At the start and end of each treatment period, patients received an oral fat load (unsweetened fresh cream) after a ≥12 hour overnight fast. Before and at several time points after consumption of the fat load, venous blood samples were collected.

Outcomes

The primary endpoint was the 8-hour post–fat load area under the curve (AUC) in non–HDL-c level (the AUC reflects the total exposure of atherogenic lipoproteins in FD after the oral fat load). Secondary endpoints included fasting and post–fat load levels of lipids and lipoproteins.

In addition, the proportion of patients who achieved their non–HDL-c treatment goals (defined as <131 mg/dL [<3.4 mmol/L] for FD patients without CVD and <100 mg/dL [<2.6 mmol/L] for FD patients with established CVD or T2DM) was calculated. The safety of evolocumab was assessed by monitoring adverse events.

Main results

Fasting lipids and lipoproteins

Post–fat load lipids and lipoproteins

Non–HDL-c treatment goals

Adverse events

Conclusion

In an RCT with 28 FD patients, evolocumab added to standard lipid-lowering therapy resulted in significant and clinically relevant reductions in fasting and absolute post–fat load levels of lipids and lipoproteins, including non–HDL-c and apoB, compared with placebo. However, evolocumab had no effect on the postprandial rise in lipid and lipoprotein levels during the 8 hours after an oral fat load. Almost all patients achieved their non–HDL-c treatment goals after treatment with evolocumab.

References

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Find this article online at J Clin Lipidol.

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