title: Investigational therapies for the treatment of atherosclerosis.
abstract: BACKGROUND
  There is great need for new drugs to reduce cholesterol in those patients who have not achieved target levels on statins as well as those who are statin intolerant.
  
  
  METHODS
  In this review, the authors discuss the new antisense oligotide inhibitor of apo B synthesis, mipomersen; pro-protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and cholesterol ester transport protein (CETP) inhibitors. Furthermore, the authors discuss cholesterol absorption and chylomicron synthesis with an emphasis on microsomal triglyceride transfer protein (MTP) inhibitors, which inhibit very-low-density lipoprotein production in the liver and chylomicron inhibition in the intestine. Finally, the authors also discuss Apo A1- and adenosine triphosphate-binding cassette transporter A1 (ABCA1)-promoting drugs. A literature review was performed through PubMed using the terms atherosclerosis, hypercholesterolemia, Apo B inhibition, PSCK9, CETP inhibitors, MTP inhibitors, apo A1 mimetics and ABCA1.
  
  
  CONCLUSIONS
  So far, research suggests that PCSK9 inhibitors will be successful with mipomersen being used for those patients who do not respond well or who are still not at target. However, it is difficult to see where CETP inhibitors will fit in except with patients who have very low high-density lipoprotein. The MTP inhibitor lomitapide is currently only licensed for familial homozygous hypercholesterolemia but the intestinal inhibitors may have a future, particularly in familial combined hyperlipidemia. The future will be most exciting.
authors.affiliation: Diabetes Institute of Ireland, Beacon Hospital , Clontra, Quinns Road, Shankill, Dublin 18 , Ireland +00 353 1 2390658 ; +00 353 1 2721395 ; gerald.tomkin@tcd.ie.
authors.forename: Gerald H
authors.initials: GH
authors.lastname: Tomkin
authors.forename: Daphne
authors.initials: D
authors.lastname: Owens
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D015195:Drug Design; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000473:pathology
chemical_list: D000924:Anticholesteremic Agents; D015507:Drugs, Investigational; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol
keywords: ABCA1; Apo A1 mimetics; apo B synthesis; atherosclerosis; cholesterol ester transfer protein; high-density lipoprotein; microsomal triglyceride transfer protein; mipomersen; pro-protein convertase subtilisin/kexin type 9 inhibitors