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JOURNAL ARTICLE
REVIEW
Anacetrapib, a cholesterol ester transfer protein (CETP) inhibitor for the treatment of atherosclerosis.
Current Opinion in Investigational Drugs 2009 September
Anacetrapib, under development by Merck & Co Inc, is an inhibitor of the cholesterol ester transfer protein (CETP) for the treatment of atherosclerosis. By reversibly increasing the affinity of CETP for lipoprotein particles, anacetrapib inhibits CETP-mediated cholesterol exchange, resulting in elevated HDL-cholesterol levels and reductions in LDL-cholesterol levels. In phase I and II clinical trials, anacetrapib was well tolerated and, unlike the now discontinued CETP inhibitor torcetrapib, did not affect blood pressure and aldosterone levels. The impact of anacetrapib on lipoprotein parameters was superior to that of the CETP inhibitors torcetrapib and dalcetrapib. However, while anacetrapib displays promising anti-arteriosclerotic properties, the long-term safety and tolerability of the agent remains to be evaluated. Moreover, the concept that inhibiting CETP is atheroprotective is yet to be proven. The future of CETP inhibitors has also been affected by the failure of torcetrapib, which increased mortality in a phase III trial. Results from an ongoing phase III trial of anacetrapib will determine the likely future development of not only anacetrapib, but of the pharmacological class of CETP inhibitors.
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