The cholesteryl ester transfer protein (CETP) inhibitor anacetrapib reduces LDL-cholesterol levels by nearly 40% and more than doubles HDL-cholesterol levels in patients with, or at high risk of, coronary heart disease. Furthermore, unlike torcetrapib—the first of the CETP inhibitors to be developed—anacetrapib has an acceptable safety profile. These findings from the DEFINE trial show great promise for this new agent. “There are very few drugs available to treat low levels of good cholesterol,” says senior investigator Christopher Cannon, “anacetrapib is four to ten times more effective in raising good cholesterol compared with current therapies.”
Inhibitors of CETP prevent the transport of cholesterol from HDL to LDL particles, thereby increasing levels of HDL cholesterol and reducing levels of LDL cholesterol. However, the early potential of this class of drugs was undermined in 2007 by the results of ILLUMINATE. After much anticipation of practice-changing results, this study showed that torcetrapib substantially increased the risk of mortality and cardiovascular events, and increased blood pressure and levels of aldosterone. The development of torcetrapib was discontinued and the future of CETP inhibitors seemed bleak, but anacetrapib was waiting in the wings. Early clinical studies of this new drug showed that it had none of the adverse effects of torcetrapib, indicating that these safety issues were not a class effect of CETP inhibitors, but perhaps unique to torcetrapib and unrelated to the primary mechanism of action.
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