Mipomersen, an apolipoprotein B synthesis inhibitor, lowers low-density lipoprotein cholesterol in high-risk statin-intolerant patients: a randomized, double-blind, placebo-controlled trial.
Eur Heart J
; 33(9): 1142-9, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22507979
ABSTRACT
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 ANDRESULTS:
Thirty-three subjects, not receiving statin therapy because of statin intolerance, received a weekly subcutaneous dose of 200 mg mipomersen or placebo (21 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 ≥ 3× 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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
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2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
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Inibidores de Hidroximetilglutaril-CoA Redutases
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Apolipoproteína B-100
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Hipercolesterolemia
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LDL-Colesterol
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Anticolesterolemiantes
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Eur Heart J
Ano de publicação:
2012
Tipo de documento:
Article