PMID- 31648705
OWN - NLM
STAT- MEDLINE
DCOM- 20200608
LR  - 20200608
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Linking)
VI  - 74
IP  - 17
DP  - 2019 Oct 29
TI  - Long-Term Efficacy and Safety of Evolocumab in Patients With 
      Hypercholesterolemia.
PG  - 2132-2146
LID - S0735-1097(19)37460-1 [pii]
LID - 10.1016/j.jacc.2019.08.1024 [doi]
AB  - BACKGROUND: Evolocumab and other anti-PCSK9 antibodies reduced adverse 
      cardiovascular outcomes in clinical trials of high-risk patients over <3 years 
      median treatment duration. OBJECTIVES: The OSLER-1 trial (Open Label Study of 
      Long Term Evaluation Against LDL-C Trial) evaluated longer-term effects of 
      evolocumab during open-label hypercholesterolemia treatment for up to 5 years. 
      METHODS: Patients randomized to standard of care (SOC) or evolocumab 420 mg 
      monthly (evolocumab + SOC) for year 1. After year 1, patients could enter the 
      all-evolocumab period and receive evolocumab + SOC for an additional 4 years. 
      The authors analyzed the persistence of lipid effects and exposure-dependent 
      safety focusing on yearly rates of adverse events (AEs) and anti-drug antibodies 
      over 4.951 patient-years of observation. RESULTS: A total of 1,255 patients 
      (safety analysis population) randomized into the year 1 SOC-controlled period and 
      received >/=1 evolocumab dose (mean +/- SD age 57 +/- 12 years; 53% female). A total of 
      1,151 patients (efficacy analysis population) progressed to the all-evolocumab 
      period (year 2 and beyond). Evolocumab + SOC persistently lowered mean +/- SE 
      low-density lipoprotein cholesterol (LDL-C) by 56% +/- 0.6% (n = 1,071), 57% +/- 0.8% 
      (n = 1,001), 56% +/- 0.8% (n = 943), and 56% +/- 0.8% (n = 803) after approximately 
      2, 3, 4, and 5 years, respectively, from randomization. Mean baseline LDL-C 
      decreased from 140 to 61 mg/dl on treatment. Yearly serious AE rates during 
      evolocumab + SOC ranged from 6.9% to 7.9%, comparable to the 6.8% rate in SOC 
      patients during year 1. Evolocumab discontinuation due to AEs occurred in 5.7% of 
      patients. Two SOC and 2 evolocumab + SOC patients developed new, transient, 
      binding anti-drug antibodies; no neutralizing antibodies were observed. 
      CONCLUSIONS: The OSLER-1 trial demonstrated consistently excellent LDL-C-lowering 
      efficacy, tolerance, and safety of evolocumab, with no neutralizing antibodies 
      detected, throughout the longest-duration study of a PCSK9 inhibitor reported to 
      date. (Open Label Study of Long Term Evaluation Against LDL-C Trial [OSLER-1]; 
      NCT01439880).
CI  - Copyright (c) 2019 The Authors. 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 - Sabatine, Marc S
AU  - Sabatine MS
AD  - Thrombolysis In Myocardial Infarction (TIMI) Study Group, Division of 
      Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, Massachusetts.
FAU - Giugliano, Robert P
AU  - Giugliano RP
AD  - Thrombolysis In Myocardial Infarction (TIMI) Study Group, Division of 
      Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, Massachusetts.
FAU - Langslet, Gisle
AU  - Langslet G
AD  - Lipid Clinic, Oslo University Hospital, Oslo, Norway.
FAU - Wiviott, Stephen D
AU  - Wiviott SD
AD  - Thrombolysis In Myocardial Infarction (TIMI) Study Group, Division of 
      Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, Massachusetts.
FAU - Ruzza, Andrea
AU  - Ruzza A
AD  - Amgen, One Amgen Center Drive, Thousand Oaks, California.
FAU - Ma, Yuhui
AU  - Ma Y
AD  - Amgen, One Amgen Center Drive, Thousand Oaks, California.
FAU - Hamer, Andrew W
AU  - Hamer AW
AD  - Amgen, One Amgen Center Drive, Thousand Oaks, California.
FAU - Wasserman, Scott M
AU  - Wasserman SM
AD  - Amgen, One Amgen Center Drive, Thousand Oaks, California.
FAU - Raal, Frederick J
AU  - Raal FJ
AD  - The Carbohydrate and Lipid Metabolism Research Unit, Faculty of Health Sciences, 
      University of the Witwatersrand, Johannesburg, South Africa.
LA  - eng
SI  - ClinicalTrials.gov/NCT01439880
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Anticholesteremic Agents)
RN  - LKC0U3A8NJ (evolocumab)
SB  - IM
CIN - J Am Coll Cardiol. 2019 Oct 29;74(17):2147-2149. PMID: 31648706
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*adverse effects/*therapeutic use
MH  - Antibodies, Neutralizing/blood
MH  - Anticholesteremic Agents/therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Hypercholesterolemia/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Patient Safety
MH  - Risk
MH  - Treatment Outcome
OTO - NOTNLM
OT  - LDL-cholesterol
OT  - PCSK9
OT  - evolocumab
OT  - lipoproteins
OT  - randomized controlled trial
EDAT- 2019/10/28 06:00
MHDA- 2020/06/09 06:00
CRDT- 2019/10/26 06:00
PHST- 2019/03/07 00:00 [received]
PHST- 2019/07/16 00:00 [revised]
PHST- 2019/08/04 00:00 [accepted]
PHST- 2019/10/26 06:00 [entrez]
PHST- 2019/10/28 06:00 [pubmed]
PHST- 2020/06/09 06:00 [medline]
AID - S0735-1097(19)37460-1 [pii]
AID - 10.1016/j.jacc.2019.08.1024 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2019 Oct 29;74(17):2132-2146. doi: 
      10.1016/j.jacc.2019.08.1024.