PMID- 24598985
OWN - NLM
STAT- MEDLINE
DCOM- 20151102
LR  - 20230622
IS  - 1522-9645 (Electronic)
IS  - 0195-668X (Linking)
VI  - 35
IP  - 33
DP  - 2014 Sep 1
TI  - Efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to 
      PCSK9, in hyperlipidaemic patients on various background lipid therapies: pooled 
      analysis of 1359 patients in four phase 2 trials.
PG  - 2249-59
LID - 10.1093/eurheartj/ehu085 [doi]
AB  - AIMS: Prior trials with monoclonal antibodies to proprotein convertase 
      subtilizin/kexin type 9 (PCSK9) reported robust low density lipoprotein 
      cholesterol (LDL-C) reductions. However, the ability to detect potentially 
      beneficial changes in other lipoproteins such as lipoprotein (a), triglycerides, 
      high-density lipoprotein cholesterol (HDL-C), and apolipoprotein (Apo) A1, and 
      adverse events (AEs) was limited by sample sizes of individual trials. We report 
      a pooled analysis from four phase 2 studies of evolocumab (AMG 145), a monoclonal 
      antibody to PCSK9. METHODS AND RESULTS: The trials randomized 1359 patients to 
      various doses of subcutaneous evolocumab every 2 weeks (Q2W) or 4 weeks (Q4W), 
      placebo, or ezetimibe for 12 weeks; 1252 patients contributed to efficacy and 
      1314, to safety analyses. Mean percentage (95% CI) reductions in LDL-C vs. 
      placebo ranged from 40.2% (44.6%, 35.8%) to 59.3% (63.7%, 54.8%) among the 
      evolocumab groups (all P < 0.001). Statistically significant reductions in 
      apolipoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), 
      triglycerides and lipoprotein (a) [Lp(a)], and increases in HDL-C were also 
      observed. Adverse events (AEs) and serious AEs with evolocumab were reported in 
      56.8 and 2.0% of patients, compared with 49.2% and 1.2% with placebo. Adjudicated 
      cardiac and cerebrovascular events were reported in 0.3 and 0% in the placebo and 
      0.9 and 0.3% in the evolocumab arms, respectively. CONCLUSION: In addition to 
      LDL-C reduction, evolocumab, dosed either Q2W or Q4W, demonstrated significant 
      and favourable changes in other atherogenic and anti-atherogenic lipoproteins, 
      and was well tolerated over the 12-week treatment period.
CI  - Published on behalf of the European Society of Cardiology. All rights reserved. (c) 
      The Author 2014. For permissions please email: journals.permissions@oup.com.
FAU - Stein, Evan A
AU  - Stein EA
AD  - Metabolic and Atherosclerosis Research Centre, Cincinnati, OH, USA 
      esteinmrl@aol.com.
FAU - Giugliano, Robert P
AU  - Giugliano RP
AD  - TIMI Study Group, Brigham and Women's Hospital, Boston, MA, USA.
FAU - Koren, Michael J
AU  - Koren MJ
AD  - Jacksonville Centre for Clinical Research, Jacksonville, FL, USA.
FAU - Raal, Frederick J
AU  - Raal FJ
AD  - Carbohydrate & Lipid Metabolism Research Unit, University of Witwatersrand, 
      Johannesburg, South Africa.
FAU - Roth, Eli M
AU  - Roth EM
AD  - Sterling Research Group, Cincinnati, OH, USA.
FAU - Weiss, Robert
AU  - Weiss R
AD  - Maine Research Associates, Auburn, ME, USA.
FAU - Sullivan, David
AU  - Sullivan D
AD  - Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Camperdown, 
      Australia.
FAU - Wasserman, Scott M
AU  - Wasserman SM
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Somaratne, Ransi
AU  - Somaratne R
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Kim, Jae B
AU  - Kim JB
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Yang, Jingyuan
AU  - Yang J
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Liu, Thomas
AU  - Liu T
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Albizem, Moetaz
AU  - Albizem M
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Scott, Rob
AU  - Scott R
AD  - Amgen Inc., Thousand Oaks, CA, USA.
FAU - Sabatine, Marc S
AU  - Sabatine MS
AD  - TIMI Study Group, Brigham and Women's Hospital, Boston, MA, USA.
CN  - PROFICIO Investigators
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20140304
PL  - England
TA  - Eur Heart J
JT  - European heart journal
JID - 8006263
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Azetidines)
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  - EOR26LQQ24 (Ezetimibe)
RN  - LKC0U3A8NJ (evolocumab)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal/*administration & dosage/adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - Anticholesteremic Agents/*administration & dosage/adverse effects
MH  - Azetidines/*administration & dosage
MH  - Clinical Trials, Phase II as Topic
MH  - Ezetimibe
MH  - Female
MH  - Humans
MH  - Hyperlipidemias/*drug therapy
MH  - Lipid Metabolism/drug effects
MH  - Male
MH  - Middle Aged
MH  - Proprotein Convertase 9
MH  - Proprotein Convertases/*immunology
MH  - Randomized Controlled Trials as Topic
MH  - Serine Endopeptidases/*immunology
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Low-density lipoprotein cholesterol
OT  - Proprotein convertase subtilizin/kexin type 9
OT  - Randomized controlled trials
EDAT- 2014/03/07 06:00
MHDA- 2015/11/03 06:00
CRDT- 2014/03/07 06:00
PHST- 2014/03/07 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2015/11/03 06:00 [medline]
AID - ehu085 [pii]
AID - 10.1093/eurheartj/ehu085 [doi]
PST - ppublish
SO  - Eur Heart J. 2014 Sep 1;35(33):2249-59. doi: 10.1093/eurheartj/ehu085. Epub 2014 
      Mar 4.