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

• 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
• Journal Title: Cardiovascular Drugs and Therapy
• Volume: Volume 30, Number 3
• Publisher: Springer Verlag (Germany) | 2016-05-30, Pages 305-313
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1007/s10557-016-6666-1
• Subjects: Health Sciences, Immunology; Health Sciences, Medicine and Surgery
• Keywords: Science & Technology; Life Sciences & Biomedicine; Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy; Cardiovascular System & Cardiology; Apolipoprotein; High-density lipoprotein; Low-density lipoprotein-cholesterol; Proprotein convertase subtilisin/kexin type 9; Triglycerides; SUBTILISIN/KEXIN TYPE 9; NON-HDL CHOLESTEROL; HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; PLACEBO-CONTROLLED TRIAL; STATIN-TREATED PATIENTS; MONOCLONAL-ANTIBODY; LDL-C; CARDIOVASCULAR-DISEASE; RANDOMIZED-TRIAL; AMG 145

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.