title: Efficacy and Safety of the PCSK9 Inhibitor Evolocumab in Patients with Mixed Hyperlipidemia.
abstract: Evolocumab significantly reduces low-density lipoprotein-cholesterol (LDL-C); we investigated its effects on LDL-C lowering in patients with mixed hyperlipidemia.
  
  
  
  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.
  
  
  
  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 −65 % vs. placebo and −39 % vs. ezetimibe, [corrected]  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).
  
  
  
  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.
authors.affiliation: Mount Sinai Heart, Cardiometabolics Unit, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, MC1 Level, New York, NY, 10029, USA. robert.rosenson@mssm.edu.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Rosenson
authors.affiliation: Emory University, 201 Dowman Drive, Atlanta, GA, 30322, USA.
authors.forename: Terry A
authors.initials: TA
authors.lastname: Jacobson
authors.affiliation: Clinical Trial Service Unit and Epidemiological Studies Unit, Oxford University, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford, OX3 7LF, UK.
authors.forename: David
authors.initials: D
authors.lastname: Preiss
authors.affiliation: Amgen Inc., One Amgen Center Dr, Thousand Oaks, CA, 91320, USA.
authors.forename: C Stephen
authors.initials: CS
authors.lastname: Djedjos
authors.affiliation: Amgen (Europe) GmbH, Dammstrasse 23, 6300, Zug, Switzerland.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Dent
authors.affiliation: Amgen Ltd, 240 Cambridge Science Park, Milton, Cambridge, CB4 0WD, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Bridges
authors.affiliation: University of Maryland School of Medicine, 655 W Baltimore St, Baltimore, MD, 21201, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001055:Apolipoproteins B / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004311:Double-Blind Method; D000069438:Ezetimibe / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D000091362:PCSK9 Inhibitors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D055815:Young Adult; D000071449:Proprotein Convertase 9
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D002784:Cholesterol; D000069438:Ezetimibe; D000091362:PCSK9 Inhibitors; D014280:Triglycerides; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; C577155:evolocumab
keywords: Apolipoprotein; High-density lipoprotein; Low-density lipoprotein-cholesterol; Proprotein convertase subtilisin/kexin type 9; Triglycerides