Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone.

ABSTRACT:

Background and purpose

Inhibition of cholesteryl ester transfer protein (CETP) with torcetrapib in humans increases plasma high density lipoprotein (HDL) cholesterol levels but is associated with increased blood pressure. In a phase 3 clinical study, evaluating the effects of torcetrapib in atherosclerosis, there was an excess of deaths and adverse cardiovascular events in patients taking torcetrapib. The studies reported herein sought to evaluate off-target effects of torcetrapib.

Experimental approach

Cardiovascular effects of the CETP inhibitors torcetrapib and anacetrapib were evaluated in animal models.

Key results

Torcetrapib evoked an acute increase in blood pressure in all species evaluated whereas no increase was observed with anacetrapib. The pressor effect

SUBMITTER: Forrest MJ 

PROVIDER: S-EPMC2440088 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature