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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:257.)
© 2007 American Heart Association, Inc.

Editorials

The Failure of Torcetrapib

Was it the Molecule or the Mechanism?

Alan R. Tall; Laurent Yvan-Charvet; Nan Wang

From the College of Physicians and Surgeons, Columbia University, New York.

Correspondence to Alan R. Tall, Columbia University, College of Physicians and Surgeons, New York, NY 10032. E-mail art1@columbia.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Hopes have been running high that treatments aimed at raising HDL levels would soon help to reduce the large burden of cardiovascular disease that remains in patients at high risk of CHD who are now treated with statins. The unexpected and premature termination of the ILLUMINATE study has dashed those hopes. This study was designed to determine the clinical outcome of raising HDL by treatment with the CETP inhibitor torcetrapib in combination with atorvastatin. It had enrolled approximately 15 000 patients at high CHD risk who were randomized to treatment with torcetrapib (60 mg) plus atorvastatin versus atorvastatin alone (10 to 80 mg). As reported in the Wall Street Journal (Dec 4th), the study was terminated abruptly and unexpectedly after a little more than a year of treatment, because of an excess of deaths in the torcetrapib/atorvastatin versus atorvastatin groups (82 versus 51, respectively). Increases in heart failure, angina, and revascularization procedures were also observed. So is this the awakening from a dream of a highly effective way to raise HDL, or is it simply a nightmare created by unintended pharmacological effects of this particular CETP inhibitor? There is no clear answer to this question yet, but it is of interest to trace the development of CETP inhibitors, to reflect on the potential underlying reasons for the failure, and to ask if there is a way forward.

The idea of inhibiting CETP as a therapy to increase HDL and lower LDL levels emerged from studies that elucidated human genetic deficiency . . . [Full Text of this Article]

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