Cardiovascular Drugs and Therapy

, Volume 27, Issue 6, pp 559–567 | Cite as

New Therapies Targeting apoB Metabolism for High-Risk Patients with Inherited Dyslipidaemias: What Can the Clinician Expect?

  • Amirhossein Sahebkar
  • Gerald F. Watts


Apolipoprotein B (apoB) has a key role in the assembly and secretion of very low-density lipoprotein (VLDL) from the liver. Plasma apoB concentration affects the number of circulating atherogenic particles, and serves as an independent predictor of the risk of atherosclerotic cardiovascular disease. While statins are the most potent apoB-lowering agents currently prescribed, their efficacy in achieving therapeutic targets for low-density lipoprotein cholesterol (LDL-C) in high-risk patients, such as those with familial hypercholesterolaemia (FH), is limited. Resistance and intolerance to statins also occurs in a significant number of patients, necessitating new types of lipid-lowering therapies. Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9; AMG 145 and REGN727), a sequence-specific antisense oligonucleotide against apoB mRNA (mipomersen) and a synthetic inhibitor of microsomal triglyceride transfer protein (MTTP; lomitapide) have been tested in phase III clinical trials, particularly in patients with FH. The trials demonstrated the efficacy of these agents in lowering apoB, LDL-C, non-high-density lipoprotein cholesterol and lipoprotein(a) by 32–55 %, 37–66 %, 38–61 % and 22–50 % (AMG 145), 21–68 %, 29–72 %, 16–60 % and 8–36 % (REGN727), 16–71 %, 15–71 %, 12–66 % and 23–49 % (mipomersen) and 24–55 %, 25–51 %, 27–50 % and 15–19 % (lomitapide), respectively. Monoclonal antibodies against PCSK9 have an excellent safety profile and may be indicated not only in heterozygous FH, but also in statin-intolerant patients and those with other inherited dyslipidemias, such as familial combined hyperlipidaemia and familial elevation in Lp(a). Mipomersen and lomitapide increase hepatic fat content and are at present indicated for treating adult patients with homozygous FH alone.


Dyslipidaemia Apolipoproteins Cholesterol Monoclonal antibody Antisense oligonucleotide Randomized controlled trial 


Conflict of interest

GFW has received lecture fees from Genzyme and has served as an advisor to Sanofi-Aventis, Genzyme and Amgen Corporation.


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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Biotechnology Research CenterMashhad University of Medical SciencesMashhadIran
  2. 2.Department of Modern Sciences and TechnologiesMashhad University of Medical SciencesMashhadIran
  3. 3.Metabolic Research Centre and Lipid Disorders Clinic, Royal Perth Hospital, School of Medicine and PharmacologyUniversity of Western AustraliaPerthAustralia

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