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Eur Heart J. 2011 Nov;32(21):2650-9. doi: 10.1093/eurheartj/ehr148. Epub 2011 May 18.

Efficacy of apolipoprotein B synthesis inhibition in subjects with mild-to-moderate hyperlipidaemia.

Author information

1
Department of Vascular Medicine, Academic Medical Center Amsterdam, Meibergdreef 9, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.

Abstract

AIMS:

Mipomersen, an apolipoprotein (apo) B synthesis inhibitor, has been shown to produce potent reductions in apoB and LDL-cholesterol levels in animal models as well as healthy human volunteers. A randomized, double-blind, placebo-controlled, dose-escalation study was designed to evaluate the efficacy and safety of mipomersen monotherapy with or without dose loading in subjects with mild-to-moderate hyperlipidaemia.

METHODS AND RESULTS:

Fifty subjects with LDL-cholesterol levels between 119 and 266 mg/dL were enrolled into five cohorts at a 4:1 randomization ratio of active to placebo. Two 13-week dose regimens were evaluated at doses ranging from 50 to 400 mg/week. Mipomersen produced dose-dependent reductions in all apoB containing lipoproteins. In the 200 and 300 mg/week dose cohorts, mean reductions from baseline in LDL cholesterol were -45 ± 10% (P= 0.000) and -61 ± 8% (P= 0.000), corresponding to a -46 ± 11% (P= 0.000) and -61 ± 7% (P= 0.000) decrease in apoB levels. Triglyceride levels were also lowered with median reductions up to 53% (P= 0.021). The most common adverse events were injection site reactions. Seven of 40 subjects (18%) showed consecutive transaminase elevations >3× upper limit of normal. Five of these subjects received 400 mg/week, four of whom had apoB levels below the limit of detection. As a consequence, the 400 mg/week cohort was discontinued.

CONCLUSIONS:

Mipomersen administered as monotherapy in subjects with mild-to-moderate hyperlipidaemia produced potent reductions in all apoB-containing lipoproteins. Higher doses were associated with hepatic transaminase increases.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00216463.

PMID:
21593041
DOI:
10.1093/eurheartj/ehr148
[Indexed for MEDLINE]
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