Long-Term Evolocumab in Patients With Familial Hypercholesterolemia
Raul D Santos, Evan A Stein, G Kees Hovingh, Dirk J Blom, Handrean Soran, Gerald F Watts, J Antonio G López, Sarah Bray, Christopher E Kurtz, Andrew W Hamer, Frederick J Raal, Raul D Santos, Evan A Stein, G Kees Hovingh, Dirk J Blom, Handrean Soran, Gerald F Watts, J Antonio G López, Sarah Bray, Christopher E Kurtz, Andrew W Hamer, Frederick J Raal
Abstract
Background: Proprotein convertase subtilisin/kexin type 9 inhibitor therapy is a treatment option for patients with familial hypercholesterolemia (FH) who are unable to reach low-density lipoprotein cholesterol (LDL-C) goals.
Objectives: The aim of this study was to provide long-term safety and efficacy data for evolocumab in patients with homozygous FH (HoFH) and severe heterozygous FH (HeFH).
Methods: In this open-label, single-arm study, patients with HoFH or severe HeFH ≥12 years of age and on stable lipid-lowering therapy began subcutaneous evolocumab 420 mg monthly or 420 mg every 2 weeks if on lipoprotein apheresis. After 12 weeks, those not on apheresis could be up-titrated to 420 mg every 2 weeks. The primary endpoint was the incidence of treatment-emergent adverse events; secondary endpoints were changes in LDL-C and other lipids.
Results: In total, 300 patients (106 with HoFH, including 14 <18 years of age at enrollment) received evolocumab for a median of 4.1 years. Adverse events occurred in 89.3% of patients, the most common of which were nasopharyngitis, influenza, upper respiratory tract infection, and headache. 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 those with severe HeFH and was sustained over time. Of 48 patients with HoFH who were up-titrated, mean change in LDL-C improved from -19.6% at week 12 to -29.7% after 12 weeks of 420 mg every 2 weeks. The adjudicated cardiovascular event rate was 2.7% per year. Of 61 patients receiving apheresis at enrollment, 16 discontinued apheresis.
Conclusions: Evolocumab was well tolerated and effectively reduced plasma LDL-C levels in patients with HoFH and severe HeFH over a median of 4.1 years.
Keywords: LDL-C; PCSK9 inhibitor; evolocumab; familial hypercholesterolemia; lipid-lowering therapy; safety.
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Source: PubMed