2008
DOI: 10.1038/bjp.2008.229
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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: Card… Show more

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Cited by 267 publications
(215 citation statements)
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“…Mechanisms underlying torcetrapib-induced hyperaldosteronism are unclear, but in vitro studies demonstrated that in adrenal cell lines, torcetrapib stimulated aldosterone production by increasing expression of aldosterone synthase (CYP11B2) (Forrest et al, 2008;Hu et al, 2009). We previously demonstrated that adipocytes possess the enzymatic machinery to synthesize mineralocorticoids and glucocorticoids, namely CYP11B2, CYP11B1, and steroidogenic acute regulatory protein (StAR), and that they produce aldosterone and corticosteroids in basal and stimulated conditions (Briones et al, 2011(Briones et al, , 2012.…”
Section: Introductionmentioning
confidence: 99%
“…Mechanisms underlying torcetrapib-induced hyperaldosteronism are unclear, but in vitro studies demonstrated that in adrenal cell lines, torcetrapib stimulated aldosterone production by increasing expression of aldosterone synthase (CYP11B2) (Forrest et al, 2008;Hu et al, 2009). We previously demonstrated that adipocytes possess the enzymatic machinery to synthesize mineralocorticoids and glucocorticoids, namely CYP11B2, CYP11B1, and steroidogenic acute regulatory protein (StAR), and that they produce aldosterone and corticosteroids in basal and stimulated conditions (Briones et al, 2011(Briones et al, , 2012.…”
Section: Introductionmentioning
confidence: 99%
“…11 These findings suggest that the adverse effects observed with torcetrapib may be due to actions outside the sphere of lipoprotein metabolism. Furthermore, a manufacturer-sponsored phase 1 randomized controlled trial of a different CETP inhibitor, ancetrapib, found no effect on blood pressure despite a large reduction in CETP levels.…”
Section: Discussionmentioning
confidence: 98%
“…The analysis cohort excluded 59 patients who were treated with an aldosterone antagonist either at randomization or during the follow‐up period. Aldosterone was measured in dal‐OUTCOMES because another CETP inhibitor, torcetrapib, had been shown to raise aldosterone levels and to promote hypertension 21, 22. After the independent Data Safety and Monitoring Board determined that dalcetrapib had no effect on aldosterone concentrations, measurements were not performed on subsequent patients enrolled in the dal‐OUTCOMES trial.…”
Section: Methodsmentioning
confidence: 99%