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Logo of bmjThis ArticleThe BMJ
BMJ. 2007 April 7; 334(7596): 716.
PMCID: PMC1847891
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Hope is fading fast for torcetrapib

Drugs that increase serum concentrations of high density lipoprotein should theoretically help prevent cardiovascular events such as heart attack. But hope is fading fast for the new drug torcetrapib, which increases concentrations of “good” cholesterol by inhibiting cholesterol ester transfer protein. One clinical trial has already been stopped early because the new drug seemed to cause rather than prevent cardiovascular events, including deaths. Now ultrasound studies show that torceptrapib has none of the expected beneficial effects on coronary or carotid atherosclerosisatherosclerosis.

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Perhaps torceptrapib produces dysfunctional high density lipoprotein cholesterol. Or perhaps it is a vascular toxin with side effects (such as increased blood pressure) that wipe out any advantage from extra high density lipoprotein cholesterol, says a linked editorial (doi: 10.1056/NEJMe078029). More detailed analysis of the available data may provide the answer.

An equally urgent question is whether the failure of this one agent should halt development of other drugs in the same class. The authors of one study and the linked editorial agree that would be a mistake. Inhibition of cholesterol ester transfer protein was a controversial strategy from the start. But the evidence still supports further cautious exploration of agents that, unlike torceptrapib, don't increase systolic blood pressure.


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