The end of the road for CETP inhibitors after torcetrapib?
Curr Opin Cardiol
; 24(4): 364-71, 2009 Jul.
Article
em En
| MEDLINE
| ID: mdl-19522058
ABSTRACT
PURPOSE OF REVIEW Because high-density lipoprotein cholesterol (HDL-C) levels are inversely related to cardiovascular disease (CVD), raising HDL-C levels would seem intuitively valuable. However, the recent failure of the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib to decrease CVD has raised doubts regarding HDL-C raising in general and CETP inhibition in particular for CVD prevention. We briefly discuss the complexity of HDL metabolism, caveats of CETP inhibition, possible mechanisms for torcetrapib's failure, and the potential utility of other CETP inhibitors. RECENT FINDINGS:
Torcetrapib likely failed because of off-target effects, since other CETP inhibitors, such as dalcetrapib (JTT-705/R1658) or anacetrapib (MK-0859), do not increase blood pressure, a specific pressor effect of tocetrapib that appears to be CETP-independent. In small human trials of short duration, anacetrapib and dalcetrapib appear to improve the lipoprotein profile without obvious adverse effects, so far.SUMMARY:
The relationship between HDL metabolism, pharmacologic CETP inhibition, and atherosclerosis requires further elucidation. There seems to be sufficient evidence that evaluation of CETP inhibitors such as dalcetrapib and anacetrapib should proceed, if cautiously, since it remains uncertain whether the increased CVD risk with torcetrapib was related to agent-specific off-target effects or more generally to CETP inhibition as a mechanism to raise HDL.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
/
Compostos de Sulfidrila
/
Oxazolidinonas
/
Proteínas de Transferência de Ésteres de Colesterol
/
HDL-Colesterol
/
Anticolesterolemiantes
Limite:
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article