I have written several articles pertaining to a new class of cholesterol controlling medicines called CETP (cholesterol ester transfer protein) inhibitors.
CETP inhibitors can markedly raise good HDL cholesterol and moderately lower bad LDL. Most recently, all my articles have been negative given that the most clinically tested drug of this class called torcetrapib (developed by Pfizer) proved to be more harmful than beneficial. Torcetrapib markedly raised HDL, modestly lowered LDL, but increased blood pressure. When adding the positive and negative effects, more harm than good was the result. Questions were raised as to why torcetrapib was harmful. Most experts believe that torcetrapib increases levels of a blood pressure regulatory hormone called aldosterone thereby raising blood pressure. Higher chronic blood pressure then increases your risk for overall heart disease and death. Given that there are several types of HDL, scientists also wondered if the HDL produced by torcetrapib is the good kind. And lastly, the most important question to answer was whether all CETP inhibitors are harmful or is this just an isolated case to one specific drug.
To answer some of these questions, Merck just published their initial results with their own CETP inhibitor called anacetrapib. In 2 small studies totaling fewer than 100 people, high dose anacetrapib raised HDL incredibly by more than 2 fold and markedly lowered LDL by over one-third (a much more powerful cholesterol effect than seen with torcetrapib). More importantly, anacetrapib was not found to increase blood pressure.
Does this mean anacetrapib is a winner? The answer is not yet. By the numbers (LDL, HDL, and blood pressure), it is a big winner but we've sort of been there before. These small studies did not look at the real important outcomes: heart attack, stroke, and death. But then again, they were not designed for this purpose. What these smaller studies do mean is that this CETP inhibitor has potential and that anacetrapib should be investigated further. That means a larger study looking at hard clinical endpoints to evaluate potential benefit or harm. Merck appears to be headed in this direction.
One additional word for cautious optimism: we still don't fully know if the increased blood pressure was the only reason why torcetrapib was harmful. The question of whether CETP inhibitors produce protective HDL is still not fully answered, although there is some suggestion from the torcetrapib data that it is beneficial. In addition, rates of cancer and infection deaths were higher in the torcetrapib treated groups. Several proteins that are involved in our immunity are carried on HDL, and so there could be a link. The possibility that CETP inhibitors may increase these risks has not been fully ruled out.
Overall, the information released by Merck is positive. It's a step in the right direction and does give scientists more confidence to continue to investigate anacetrapib. But as I said before, it will take many several slow and cautious steps before we know if this CETP inhibitor is friend or foe.
Published On: December 20, 2007