Torcetrapib Improves Ratio of HDL to LDL Cholesterol
NEW YORK (Reuters Health) Mar 17 - Torcetrapib,
a newly developed inhibitor of cholesteryl ester transfer protein
(CETP), increases HDL cholesterol up to 91% while significantly
lowering LDL cholesterol, phase I trial results show.
Another CETP inhibitor raised HDL levels in mildly hyperlipidemic
subjects. However, animal studies showed no associated reduction in
atherosclerotic lesion formation, suggesting that more potent
inhibition of CETP will be required to lower the risk of heart disease,
Dr. Ronald W. Clark and colleagues explain in the March issue of
Arteriosclerosis, Thrombosis and Vascular Biology.
Dr. Clark's group at Pfizer Global Research and Development in Groton, Connecticut, tested torcetrapib in healthy volunteers, who were randomly assigned to placebo or torcetrapib 10, 30, 60 or 120 mg daily or 120 mg b.i.d. for 14 days.
HDL levels rose significantly after 2 weeks, ranging from 16% in the
10-mg group to 91% in the 120-mg b.i.d. group, with reciprocal
decreases in non-HDL cholesterol. LDL decreased up to 42% at the
The LDL-to-HDL ratio decreased significantly at doses of 30 mg or higher.
In an accompanying editorial, Dr. H. Bryan Brewer Jr. notes that
complete CETP inhibition promotes atherogenesis by causing accumulation
of very large dysfunctional HDL and abnormal LDL. Torcetrapib's
partial inhibition appears to prevent these gross abnormalities while
promoting an anti-atherogenic shift from low-density to high-density
Dr. Brewer, a researcher at the National Institutes of Health in
Bethesda, Maryland, concludes, "The ultimate evaluation of the
potential protection against atherosclerosis with torcetrapib
will require clinical trials using surrogate end points, including
coronary intravascular ultrasound and carotid IMT as well as hard
Arterioscler Thromb Vasc Biol 2004;24:490-497.
Reuters Health Information 2004. © 2004 Reuters Ltd.
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