<International Circulation>:  HDL-raising therapy may still have an important role in the prevention or management of cardiovascular disease. What is the current status of CETP (cholesterol ester transfer protein) inhibitors in HDL-raising therapy? 
 
    Dr Brown: We do not yet know whether inhibiting this transfer protein that removes cholesterol from LDL and HDL and puts it into the triglyceride carrying particle called very low density lipoproteins or VLDL， is indeed activity good thing to do. Is having too much CETP activity really a cause of atherosclerosis? These new drugs inhibit this transfer process. The first drug， torcetrapib， was a strong inhibitor of this transfer protein but failed to show benefit. In fact it increased death rates and the main reason for death rate increases was an increase in cardiovascular disease. That finding was a big setback for this field. The problem was that torcetrapib also raised blood pressure significantly and  increased  blood vessel tone and causing the blood vessels to react in an unfavorable way - in effect， more resistant to expansion with each pulse wave.  Torcetrapib also caused the adrenal gland to secrete more aldosterone which caused a more sustained elevation in blood pressure.  Both of these effects may have been the cause of the death rate， not the inhibitory activity against CETP  However， we don’t know if any of these effects were the most important reason for the adverse effects seen  in the trials. There are two new drugs that are under study， one of which， dalcetrapib， is an HDL-raising drug with  no measurable impact on LDL and minimal impact on triglycerides. It does not raise blood pressure and so far has had no significant adverse effects. That drug is now in trials. The problem is it seems to make the particles bigger but it raises the number of the HDL particles， only modestly. Those may be important characteristics of this drug and we won’t know the answer until we finish the clinical trials that are underway. One of these is a very large trial containing over 15 000 patients .  It is trying to determine whether this drug， dalcetrapib， actually is beneficial or not in preventing heart attacks and death from coronary disease. The second drug is anacetrapib and that drug both lowers LDL and raises HDL. It is in a smaller trial， with a little less than 3000 patients enrolled.  This study is  looking for evidence that this LDL effect can persist even when you treat with statin therapy.  Patients will be observed in that trial for at least two years.  There is about a 15 to 20 % fall in LDL cholesterol and a 40% rise in HDL cholesterol which is very significant. Ultimately if there is no evidence of longer term safety issues like blood pressure elevation or other safety problems， this drug will go into a large trial as well.  So it will be nearly two years before we know if this will be expanded into a bigger trial. It is going to be several years before we know if this drug is actually going to become available for prescription use.