Cholesteryl ester transfer protein inhibition and HDL increase: has the dream ended?

Vasilios G Athyros, Anna Kakafika, Konstantinos Tziomalos, Asterios Karagiannis, Dimitri P Mikhailidis
Expert Opinion on Investigational Drugs 2008, 17 (4): 445-9
Statins effectively lower plasma low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of vascular events. However, this benefit might be improved by dealing with other vascular risk factors such as high-density lipoprotein cholesterol (HDL-C). It follows that there has been an interest in drugs that raise plasma HDL-C levels. Among these drugs are the cholesteryl ester transfer protein (CETP) inhibitors. The first CETP inhibitor to be evaluated in an event-based trial was torcetrapib. This drug can considerably elevate serum HDL-C levels (e.g., by 72%). However, a recently published trial (ILLUMINATE) showed that torcetrapib used in combination with atorvastatin was associated with significantly more vascular events and deaths than atorvastatin alone. This finding resulted in the discontinuation of the torcetrapib development programme. The cause(s) of the adverse outcome remain speculative. It has been suggested that a significant rise in systolic blood pressure and possibly the quality of the HDL produced may be relevant. Despite this disappointing outcome it seems to be too early to close the book on CETP inhibitors because two other members of this class are being evaluated. These drugs (JTT-705 and anacetrapib) may be devoid of the adverse effect on systolic blood pressure. Eventually only appropriately designed, event-based trials, will settle the issue of whether CETP inhibitors are clinically useful.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"