Why torcetrapib failed: A possible mechanism

Analysis from nature.com:

But it is also possible that the whole idea of blocking CETP is flawed, says Moti Kashyap, who directs atherosclerosis research at the VA Medical Center in Long Beach, California.

When HDLs excrete cholesterol in the liver, they actually rely on LDLs for part of this process. So inhibiting CETP, which prevents the transfer of cholesterol from HDL to LDL, might actually cause an abnormal and irreversible accumulation of cholesterol in the body. “You’re blocking a physiologic mechanism to eliminate cholesterol and effectively constipating the pathway,” says Kashyap.