Efficacy and Safety of the PCSK9 Inhibitor Evolocumab in Patients with Mixed Hyperlipidemia

• Type of Material: Article
• Authors: Robert S. Rosenson, Icahn School of Medicine at Mount Sinai; Terry Jacobson, Emory University; David Preiss, Oxford University; C Stephen Djedjos, Amgen Inc; Ricardo Dent, Amgen Europe GmbH; Ian Bridges, Amgen Ltd; Michael Miller, University of Maryland
• Language: English
• Date: 2016-05-30
• Publisher: Springer Verlag (Germany)
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2016
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s10557-016-6666-1
• Title of Journal or Parent Work: Cardiovascular Drugs and Therapy
• ISSN: 0920-3206
• Volume: 30
• Issue: 3
• Start Page: 305
• End Page: 313
• Grant/Funding Information: Amgen Inc. funded the studies contributing to this analysis.
• Keywords: Science & Technology; MONOCLONAL-ANTIBODY; Cardiovascular System & Cardiology; Apolipoprotein; CARDIOVASCULAR-DISEASE; Triglycerides; RANDOMIZED-TRIAL; Life Sciences & Biomedicine; High-density lipoprotein; NON-HDL CHOLESTEROL; SUBTILISIN/KEXIN TYPE 9; LDL-C; Low-density lipoprotein-cholesterol; STATIN-TREATED PATIENTS; Cardiac & Cardiovascular Systems; PLACEBO-CONTROLLED TRIAL; Proprotein convertase subtilisin/kexin type 9; Pharmacology & Pharmacy; AMG 145; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology

Abstract

PURPOSE: Evolocumab significantly reduces low-density lipoprotein-cholesterol (LDL-C); we investigated its effects on LDL-C lowering in patients with mixed hyperlipidemia. METHODS: We compared the efficacy and safety of evolocumab in hypercholesterolemic patients selected from the phase 2 and 3 trials who had fasting triglyceride levels ≥1.7 mmol/L (150 mg/dL elevated triglycerides) and <1.7 mmol/L (without elevated triglycerides). Fasting triglyceride level ≥ 4.5 mmol/L at screening was an exclusion criterion for these studies, but post-enrollment triglyceride levels may have exceeded 4.5 mmol/L (400 mg/dL). Efficacy was evaluated in four phase 3 randomized studies (n = 1148) and safety from the phase 2 and 3 studies (n = 2246) and their open-label extension studies (n = 1698). Efficacy analyses were based on 12-week studies, while safety analyses included data from all available studies. Treatment differences were calculated vs. placebo and ezetimibe after pooling dose frequencies. RESULTS: Mean treatment difference in percentage change from baseline in LDL-C for participants with elevated triglycerides and those without elevated triglycerides (mean of weeks 10 and 12) with evolocumab was approximately -67 % vs. placebo and -42 % vs. ezetimibe (all P < 0.001) compared to -6 % vs. placebo and -39 % vs. ezetimibe, respectively. Treatment differences for evolocumab vs. placebo and ezetimibe followed a similar pattern for non-high-density lipoprotein (HDL-C) and apolipoprotein B. Evolocumab was well tolerated, with balanced rates of adverse events leading to discontinuation of evolocumab vs. comparator (placebo and/or ezetimibe). CONCLUSION: The significant reductions of atherogenic lipids including LDL-C, non-HDL-C, and apolipoprotein B seen with evolocumab are similar in patients with and without mixed hyperlipidemia.