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  • Title: Safety of inhibition of cholesteryl ester transfer protein with anacetrapib: the DEFINE study.
    Author: Gotto AM, Moon JE.
    Journal: Expert Rev Cardiovasc Ther; 2012 Aug; 10(8):955-63. PubMed ID: 23030283.
    Abstract:
    Inhibition of cholesteryl ester transfer protein is a strategy under investigation for raising HDL cholesterol levels and addressing residual cardiovascular risk after effective reduction of LDL cholesterol. In the Phase III DEFINE trial conducted in patients with or at high risk for coronary heart disease, anacetrapib reduced LDL cholesterol levels by 39.8% after 24 weeks compared with placebo and demonstrated an acceptable safety profile through 76 weeks of treatment (the primary end points). Anacetrapib caused a placebo-adjusted 138.1% increase in HDL cholesterol levels, with no alterations in blood pressure, aldosterone or electrolytes. The trial also provided reassurance that anacetrapib would not be associated with a 25% increase in cardiovascular events, as seen with a previous cholesteryl ester transfer protein inhibitor. Sustained effects on lipids were observed 12 weeks following cessation of anacetrapib treatment. Anacetrapib is being evaluated in an ongoing cardiovascular outcomes trial.
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