Efficacy and short-term safety of a new ACAT inhibitor, avasimibe, on lipids, lipoproteins, and apolipoproteins, in patients with combined hyperlipidemia

William Insull, Michael Koren, Jean Davignon, Dennis Sprecher, Helmut Schrott, Leonard M. Keilson, Alan S. Brown, Carlos A. Dujovne, Michael H. Davidson, Richard McLain, Therese Heinonen

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Although acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors have been shown to reduce lipid levels in several animal models, the safety and lipid modifying activity of any single agent in this class has not been demonstrated in humans. The safety and efficacy of avasimibe (CI-1011), a new, unique, wholly synthetic ACAT inhibitor, was evaluated in the treatment of 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia (low levels of high-density lipoprotein cholesterol [HDL-C]). Following an 8-week placebo and dietary-controlled baseline period, patients were randomly assigned to double-blind treatment with placebo, 50, 125, 250, or 500 mg avasimibe administered as capsules once daily for 8 weeks. At all evaluated doses, avasimibe treatment resulted in prompt and significant reductions (P < 0.05) in plasma levels of total triglycerides (TG) and very low-density lipoprotein cholesterol (VLDL-C) with mean reductions of up to 23% and 30% respectively, apparently independent of dose. No statistically significant changes in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), HDL-C or apolipoprotein (apo) B were detected. ApoAI levels were also unchanged on all doses of avasimibe apart from the 500 mg dosage, which was associated with a significant decrease in plasma apoAI. The relevance of this latter finding in only one dosage group is not known. All doses of avasimibe were well tolerated with no resulting significant abnormalities of biochemical, hematological, or clinical parameters.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalAtherosclerosis
Volume157
Issue number1
DOIs
StatePublished - 2001

Keywords

  • ACAT
  • Atherosclerosis
  • Hyperlipidemia
  • Triglycerides

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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