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Anacetrapib shows promise
Despite the success of statins for both primary and secondary prevention, many patients continue to have a high residual risk of cardiovascular events related to suboptimal lipid control. One approach to raising high-density lipoprotein (HDL) cholesterol is to inhibit cholesteryl ester transfer protein (CETP), a plasma protein that promotes the transfer of cholesteryl esters between the lipoproteins, with inhibition of CETP increasing HDL and concomitantly lowering low-density lipoprotein (LDL). The first CETP inhibitor to make it to phase III trial was torcetrapib in the ILLUMINATE study, but this was terminated early after the drug was shown to cause an excess of deaths and cardiovascular events. Analysis of these results suggested that torcetrapib was acting off-target and increasing blood pressure, and that the adverse effects were not related to CETP inhibition per se. While torcetrapib was hastily jettisoned, development on other CETP inhibitors has continued and in this large study the safety of anacetrapib was assessed.
In a randomised, double-blind, placebo controlled trial in patients with coronary heart disease or at high risk of coronary heart disease who were taking a statin, 1623 individuals were assigned to receive 100 mg anacetrapib or placebo daily for 18 months. The primary endpoints were the percentage change from baseline in LDL-cholesterol at 24 weeks (the HDL-cholesterol level was a secondary endpoint) and the safety and side-effect profile …