Evolocumab Found Effective in Reducing Plasma LDL-C in Familial Hypercholesterolemia

familial hypercholesterolemia
Treatment with evolocumab was found to be effective in reducing plasma levels of low-density lipoprotein cholesterol in familial hypercholesterolemia.

Treatment with evolocumab was found to be effective in reducing plasma levels of low-density lipoprotein cholesterol (LDL-C) in patients with homozygous familial hypercholesterolemia (HoFH) and severe heterozygous FH (HeFH), according to study results published in the Journal of the American College of Cardiology.

The study examined the efficacy and safety of evolocumab in the long-term as part of the Trial Assessing Long Term Use of PCSK9 Inhibition in Subjects With Genetic LDL Disorders trial (ClinicalTrials.gov Identifier: NCT01624142). In this open-label trial, patients with HoFH (n=106) or severe HeFH (n=194) who did not achieve target LDL-C levels despite being on stable lipid-lowering therapy, were treated with evolocumab (420-mg subcutaneous injection monthly or twice monthly in patients on lipoprotein apheresis at time of enrollment).

Patients who were not undergoing lipoprotein apheresis could receive doses every 2 weeks. In patients displaying a response to evolocumab (eg, LDL-C reduction ≥5%), evolocumab could be administered every month. The primary endpoint of this study was the incidence of treatment-emergent adverse events (TEAEs). Secondary endpoints included changes in levels of LDL-C and other lipids.

Study participants were treated with evolocumab for a median of 4.1 years. Adverse events (AEs) were reported by 83.9% of patients. The most common AEs were nasopharyngitis, influenza, upper respiratory tract infection, and headache.

The rate of positively adjudicated cardiovascular (CV) events was 2.7% per year (n=32; 2.8% in patients with HoFH; 2.6% in patients with severe HeFH). Of the 61 patients who were undergoing apheresis at baseline, 16 discontinued the therapy.

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The mean change in LDL-C from baseline to week 12 was −21.2% (-59.8 mg/dl) in patients with HoFH and −54.9% (−104.4 mg/dl) in patients with severe HeFH. Of the 48 patients with HoFH who were up-titrated, there was an improvement in the mean change in LDL-C from −19.6% at week 12 to −29.7% after 12 weeks of new dosing.

Study limitations include the lack of a randomized control and of blinding, as well as the small number of patients available for assessment after 4 years.

“Further studies in larger cohorts are needed to establish the incremental efficacy of sustained LDL-C lowering with evolocumab for prevention of CV events in patients with severe familial hypercholesterolemia,” noted the study authors.

Disclosure: This clinical trial was supported by Amgen. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Santos RD, Stein EA, Hovingh K, et al. Long-term evolocumab in patients with familial hypercholesterolemia. J Am Coll Cardiol. 2020;75(6):565-574.

This article originally appeared on The Cardiology Advisor