PMID- 22507979
OWN - NLM
STAT- MEDLINE
DCOM- 20120815
LR  - 20211021
IS  - 1522-9645 (Electronic)
IS  - 0195-668X (Print)
IS  - 0195-668X (Linking)
VI  - 33
IP  - 9
DP  - 2012 May
TI  - Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density 
      lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, 
      double-blind, placebo-controlled trial.
PG  - 1142-9
LID - 10.1093/eurheartj/ehs023 [doi]
AB  - AIMS: A randomized, double-blind, placebo-controlled study was conducted to 
      investigate the safety and efficacy of mipomersen, an apolipoprotein B-100 (apoB) 
      synthesis inhibitor, in patients who are statin intolerant and at high risk for 
      cardiovascular disease (CVD). METHODS AND RESULTS: Thirty-three subjects, not 
      receiving statin therapy because of statin intolerance, received a weekly 
      subcutaneous dose of 200 mg mipomersen or placebo (2:1 randomization) for 26 
      weeks. The primary endpoint was per cent change in LDL cholesterol (LDL-c) from 
      the baseline to Week 28. The other efficacy endpoints were per cent change in 
      apoB and lipoprotein a [Lp(a)]. Safety was determined using the incidence of 
      treatment-emergent adverse events (AEs) and clinical laboratory evaluations. 
      After 26 weeks of mipomersen administration, LDL-c was reduced by 47 +/- 18% (P < 
      0.001 vs. placebo). apoB and Lp(a) were also significantly reduced by 46 and 27%, 
      respectively (P < 0.001 vs. placebo). Four mipomersen (19%) and two placebo 
      subjects (17%) discontinued dosing prematurely due to AEs. Persistent liver 
      transaminase increases >/= 3x the upper limit of normal were observed in seven 
      (33%) subjects assigned to mipomersen. In selected subjects, liver fat content 
      was assessed, during and after treatment, using magnetic resonance spectroscopy. 
      Liver fat content in these patients ranged from 0.8 to 47.3%. Liver needle biopsy 
      was performed in two of these subjects, confirming hepatic steatosis with minimal 
      inflammation or fibrosis. CONCLUSION: The present data suggest that mipomersen is 
      a potential therapeutic option in statin-intolerant patients at high risk for 
      CVD. The long-term follow-up of liver safety is required. CLINICAL TRIAL 
      REGISTRATION: ClinicalTrials.gov identifier: NCT00707746.
FAU - Visser, Maartje E
AU  - Visser ME
AD  - Department of Vascular Medicine, Academic Medical Center, Amsterdam, The 
      Netherlands.
FAU - Wagener, Gilbert
AU  - Wagener G
FAU - Baker, Brenda F
AU  - Baker BF
FAU - Geary, Richard S
AU  - Geary RS
FAU - Donovan, Joanne M
AU  - Donovan JM
FAU - Beuers, Ulrich H W
AU  - Beuers UH
FAU - Nederveen, Aart J
AU  - Nederveen AJ
FAU - Verheij, Joanne
AU  - Verheij J
FAU - Trip, Mieke D
AU  - Trip MD
FAU - Basart, Dick C G
AU  - Basart DC
FAU - Kastelein, John J P
AU  - Kastelein JJ
FAU - Stroes, Erik S G
AU  - Stroes ES
LA  - eng
SI  - ClinicalTrials.gov/NCT00707746
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20120416
PL  - England
TA  - Eur Heart J
JT  - European heart journal
JID - 8006263
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Apolipoprotein B-100)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Oligonucleotides)
RN  - 9GJ8S4GU0M (mipomersen)
RN  - EC 2.6.1.2 (Alanine Transaminase)
SB  - IM
CIN - Eur Heart J. 2012 May;33(9):1040-3. PMID: 22507980
MH  - Adult
MH  - Aged
MH  - Alanine Transaminase/metabolism
MH  - Anticholesteremic Agents/*therapeutic use
MH  - Apolipoprotein B-100/*antagonists & inhibitors
MH  - Cardiovascular Diseases/enzymology/prevention & control
MH  - Cholesterol, LDL/*metabolism
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*adverse effects
MH  - Hypercholesterolemia/*drug therapy/enzymology
MH  - Male
MH  - Middle Aged
MH  - Oligonucleotides/*therapeutic use
MH  - Risk Factors
MH  - Treatment Outcome
PMC - PMC3751967
EDAT- 2012/04/18 06:00
MHDA- 2012/08/16 06:00
PMCR- 2013/05/01
CRDT- 2012/04/18 06:00
PHST- 2012/04/18 06:00 [entrez]
PHST- 2012/04/18 06:00 [pubmed]
PHST- 2012/08/16 06:00 [medline]
PHST- 2013/05/01 00:00 [pmc-release]
AID - ehs023 [pii]
AID - 10.1093/eurheartj/ehs023 [doi]
PST - ppublish
SO  - Eur Heart J. 2012 May;33(9):1142-9. doi: 10.1093/eurheartj/ehs023. Epub 2012 Apr 
      16.