Details

Autor(en) / Beteiligte

• Vergeer, Menno, MD
• Stroes, Erik S.G., MD, PhD

Titel

The Pharmacology and Off-Target Effects of Some Cholesterol Ester Transfer Protein Inhibitors

Ist Teil von

• The American journal of cardiology, 2009-11, Vol.104 (10), p.32E-38E

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2009

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Inhibitors of cholesterol ester transfer protein (CETP) have the capacity to increase plasma high-density lipoprotein cholesterol to unprecedented levels. Still, hopes that CETP inhibition could reduce atherosclerosis were dented when the clinical development of one such inhibitor, torcetrapib, was halted because of an unexpected finding of increased cardiovascular and noncardiovascular mortality against a background of elevated blood pressure and plasma aldosterone levels. Recently, evidence has accumulated to show that these untoward effects may have been largely attributable to off-target toxicity of the compound, unrelated to the mechanism of CETP inhibition and not shared by other CETP inhibitors. In this review, we explore the rationale for CETP inhibition, compare the pharmacology of the small molecule CETP inhibitors that reached clinical development, and address the evidence relating to off-target adverse effects.