HDL has long been praised as the “good cholesterol,” as opposed to its evil twin LDL, aka the “bad cholesterol.” Low levels of HDL and high levels of LDL are associated with increased risk of heart disease. High levels of HDL are thought to be protective against heart disease and can offset some of the risk associated with having high LDL levels, or so we think. A recent study published in JAMA by Ruth Frikke-Schmidt and colleagues is challenging the notion that having low HDL levels is harmful. This study, which looked at patients with genetically low levels of HDL due to mutations in a gene called ABCA1, found no increased risk of heart disease after 30 years of follow up.

The results of this study can weaken the arguments about the protective effects of HDL and raise doubts about the success of designing drugs that increase HDL levels. You may remember what happened to Pfizer’s torcetrapib, a drug that was talked up to be the next big thing for the company. Despite significantly increasing HDL levels, torcetrapid actually ended up increasing the risk of death and heart attacks, leading Pfizer to halt its entire program. Some experts noted that the adverse effects of torcetrapib may have been due to the fact that it raised the patients’ blood pressure. Merck currently has a drug like torcetrapib called anacetrapib under development, which reportedly increases HDL levels without raising blood pressure.

With Pfizer’s disappointing experience with torcetrapib and Frikke-Schmidt’s new study, Merck may be on the wrong track. I wonder if we should spend more resources in promoting better-proven ways of reducing the risk of heart disease, such as eating healthy and exercising. Easy to say, I know. I too sometimes wish for a magic pill.

More info: torcetrapib, anacetrapid

Filed under: Pharma/Biotech