The potential of mipomersen, an ApoB synthesis inhibitor, to reduce necessity for LDL-apheresis in patients with heterozygous familial hypercholesterolemia and coronary artery disease.

Abstract

INTRODUCTION:

LDL-apheresis is a treatment option for familial hypercholesterolemia (FH) with country-specific thresholds for LDL-cholesterol (LDL-C) for initiation. Apheresis also reduces lipoprotein(a) [Lp(a)] and may be used to lower Lp(a) in high-risk patients. Mipomersen, an apolipoproteinB-synthesis-inhibitor, reduces LDL-C and Lp(a). We hypothesized that mipomersen may prevent the necessity for apheresis by reducing the both below thresholds.

METHODS:

Data from a study in 123 patients with heterozygous FH and coronary artery disease on maximally tolerated lipid-lowering therapy were used to evaluate in what percentage adding mipomersen resulted in lipid-levels below apheresis-thresholds. Different thresholds were tested: LDL-C ≥ 2.59 mmol/l, ≥ 3.36 mmol/l, ≥ 4.14 mmol/l, Lp(a) ≥ 60 mg/dl.

RESULTS:

Mipomersen decreased LDL-C by 28% (baseline 153 mg/dl), Lp(a) by 21% (baseline 45 mg/dl) (placebo no effect). Mipomersen reduced the percentage of patients with LDL-C ≥ 4.14 mmol/l from 39 to 2%, with LDL ≥ 3.36 mmol/l from 62 to 16%, with LDL ≥ 2.59 mmol/l from 98 to 54%, and with Lp(a) ≥ 60 mg/dl from 39 to 23%.

SUMMARY:

When added to maximally tolerated lipid-lowering therapy, mipomersen may reduce the necessity for apheresis in many of these patients. In Germany, the threshold for apheresis for LDL typically is 2.59 mmol/l, for Lp(a) 60 mg/dl. Almost 50% of the patients could avoid apheresis with the addition of mipomersen. Further studies are warranted to evaluate whether patients who qualify for apheresis could be adequately controlled with mipomersen.

• Authors: Anja Vogt, Klaus G Parhofer
• Journal: Expert opinion on pharmacotherapy (Expert Opin Pharmacother) Vol. 14 Issue 6 Pg. 691-7 (Apr 2013) ISSN: 1744-7666 [Electronic] England
• PMID: 23477485 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anticholesteremic Agents
• Apolipoproteins B
• Cholesterol, LDL
• Oligonucleotides
• mipomersen

Topics

• Aged
• Anticholesteremic Agents (pharmacology, therapeutic use)
• Apolipoproteins B (biosynthesis)
• Blood Component Removal (methods)
• Cholesterol, LDL (blood)
• Coronary Artery Disease (drug therapy, physiopathology)
• Female
• Germany
• Humans
• Hyperlipoproteinemia Type II (drug therapy, physiopathology)
• Male
• Middle Aged
• Oligonucleotides (pharmacology, therapeutic use)