PMID- 24691094
OWN - NLM
STAT- MEDLINE
DCOM- 20140828
LR  - 20230622
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Linking)
VI  - 63
IP  - 23
DP  - 2014 Jun 17
TI  - Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, 
      controlled phase III clinical trial of evolocumab.
PG  - 2531-2540
LID - S0735-1097(14)01727-6 [pii]
LID - 10.1016/j.jacc.2014.03.018 [doi]
AB  - OBJECTIVES: The aim of this study was to compare biweekly and monthly evolocumab 
      with placebo and oral ezetimibe in patients with hypercholesterolemia in a phase 
      III trial. BACKGROUND: Evolocumab, a fully human monoclonal antibody against 
      proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced 
      LDL-C in phase II trials. METHODS: Patients 18 to 80 years of age with fasting 
      low-density lipoprotein cholesterol (LDL-C) >/=100 and <190 mg/dl and Framingham 
      risk scores </=10% were randomized (1:1:1:1:2:2) to oral placebo and subcutaneous 
      (SC) placebo biweekly; oral placebo and SC placebo monthly; ezetimibe and SC 
      placebo biweekly; ezetimibe and SC placebo monthly; oral placebo and evolocumab 
      140 mg biweekly; or oral placebo and evolocumab 420 mg monthly. RESULTS: A total 
      of 614 patients were randomized and administered doses. Evolocumab treatment 
      reduced LDL-C from baseline, on average, by 55% to 57% more than placebo and 38% 
      to 40% more than ezetimibe (p < 0.001 for all comparisons). Evolocumab treatment 
      also favorably altered other lipoprotein levels. Treatment-emergent adverse 
      events (AEs), muscle-related AEs, and laboratory abnormalities were comparable 
      across treatment groups. CONCLUSIONS: In the largest monotherapy trial using a 
      PCSK9 inhibitor to date, evolocumab yielded significant LDL-C reductions compared 
      with placebo or ezetimibe and was well tolerated in patients with 
      hypercholesterolemia. (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C 
      in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 
      [MENDEL-2]; NCT01763827).
CI  - Copyright (c) 2014 American College of Cardiology Foundation. Published by Elsevier 
      Inc. All rights reserved.
FAU - Koren, Michael J
AU  - Koren MJ
AD  - Jacksonville Center for Clinical Research, Jacksonville, Florida. Electronic 
      address: mkoren@encoredocs.com.
FAU - Lundqvist, Pernille
AU  - Lundqvist P
AD  - Center for Clinical and Basic Research, Ballerup, Denmark.
FAU - Bolognese, Michael
AU  - Bolognese M
AD  - Bethesda Health Research Center, Bethesda, Maryland.
FAU - Neutel, Joel M
AU  - Neutel JM
AD  - Orange County Research Center, Tustin, California.
FAU - Monsalvo, Maria Laura
AU  - Monsalvo ML
AD  - Amgen Inc., Thousand Oaks, California.
FAU - Yang, Jingyuan
AU  - Yang J
AD  - Amgen Inc., Thousand Oaks, California.
FAU - Kim, Jae B
AU  - Kim JB
AD  - Amgen Inc., Thousand Oaks, California.
FAU - Scott, Rob
AU  - Scott R
AD  - Amgen Inc., Thousand Oaks, California.
FAU - Wasserman, Scott M
AU  - Wasserman SM
AD  - Amgen Inc., Thousand Oaks, California.
FAU - Bays, Harold
AU  - Bays H
AD  - L-MARC Research Center, Louisville, Kentucky.
CN  - MENDEL-2 Investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT01763827
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20140329
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Cholesterol, LDL)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
RN  - EC 3.4.21.- (Proprotein Convertases)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - LKC0U3A8NJ (evolocumab)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antibodies, Monoclonal/*administration & dosage
MH  - Antibodies, Monoclonal, Humanized
MH  - Apoptosis
MH  - Cholesterol, LDL/*blood
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Hypercholesterolemia/blood/*drug therapy
MH  - Injections, Subcutaneous
MH  - Male
MH  - Middle Aged
MH  - Proprotein Convertase 9
MH  - Proprotein Convertases/*antagonists & inhibitors/blood
MH  - Retrospective Studies
MH  - Serine Endopeptidases/blood
MH  - Treatment Outcome
MH  - Young Adult
OTO - NOTNLM
OT  - PCSK9 inhibition
OT  - dyslipidemia
OT  - evolocumab
OT  - monotherapy
EDAT- 2014/04/03 06:00
MHDA- 2014/08/29 06:00
CRDT- 2014/04/03 06:00
PHST- 2014/02/20 00:00 [received]
PHST- 2014/03/19 00:00 [revised]
PHST- 2014/03/19 00:00 [accepted]
PHST- 2014/04/03 06:00 [entrez]
PHST- 2014/04/03 06:00 [pubmed]
PHST- 2014/08/29 06:00 [medline]
AID - S0735-1097(14)01727-6 [pii]
AID - 10.1016/j.jacc.2014.03.018 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2014 Jun 17;63(23):2531-2540. doi: 10.1016/j.jacc.2014.03.018. 
      Epub 2014 Mar 29.