`Good' Cholesterol May Not Benefit Heart, Study Says

By Shannon Pettypiece

June 3 (Bloomberg) -- `Good' cholesterol that scientists have thought helped unclog arteries had no effect on heart disease in a study, casting doubt on a theory drugmakers have spent more than $1 billion pursuing.

Researchers studied people who have a genetic condition that causes them to produce very low levels of HDL cholesterol, expecting they'd be about twice as likely to have heart disease. Instead, they had no greater risk, according to a study published today by the Journal of the American Medical Association.

Pfizer Inc., Merck & Co. and Roche Holdings AG have spent years developing drugs that increase production of HDL cholesterol based on the theory that raising the so-called good cholesterol helps ferry artery-clogging plaque from the body. The new research throws that strategy into question and shows HDL plays no role in preventing heart attacks, said Anne Tybjaerg- Hansen, a study author and clinical biochemistry researcher at Copenhagen University Hospital.

``There is really no evidence that this method is going to work,'' said Tybjaerg-Hansen in a telephone interview. ``This theory has been around for a long time, but this study just doesn't support it.''

The reason may be that other HDL cholesterol research examined patients with high levels of triglycerides, the chemical form of fat. Triglycerides, not patients' low HDL levels, may have caused their increased heart risk, Tybjaerg-Hansen said.

Why Pfizer Flopped

This may explain why the experimental drug torcetrapib, which New York-based Pfizer spent more than $1 billion developing, raised HDL levels without providing heart benefits, the study said. Analysts had expected torcetrapib would have more than $14 billion in annual sales. Pfizer quit developing it in 2006 because it increased deaths. Whitehouse Station, New Jersey- based Merck and Basel, Switzerland-based Roche also are developing HDL-raising drugs.

Yale Mitchel, Merck vice president of cardiovascular disease research, said the study, which was small and in a rare patient population, won't persuade the company to change its plans for an HDL-raising drug given the large body of data suggesting HDL provides a benefit.

Merck has spent five years developing a drug called anacetrapib, which raises HDL by blocking the cholesterol ester transfer protein. The drug is in the third and final stage of testing necessary to gain regulatory approval.

`Too Attractive'

``The hypothesis on whether CETP inhibition is a benefit or not hasn't been tested and it is too attractive a mechanism to disregard right now,'' said Mitchel. ``We have to be careful about not over interpreting it at this point. There is a large contextual database that suggests low HDL levels are associated with an increased risk.''

Pfizer has said the company's HDL-raising research is temporarily on hold. Roche said its drug is in the final stages of testing and it will file for U.S. regulatory approval after 2011.

``We haven't had an opportunity to evaluate this study yet, but epidemiological data does show there is a strong inverse relationship between HDL and cardiovascular risk,'' said Roche spokesman Terence Hurley.

The idea that HDL helps purge artery plaque is based mostly on animal studies, which Tybjaerg-Hansen said are sometimes difficult to understand and apply to humans.

The new study looked at data collected from almost 57,000 Danish patients between 1976 and 2007, of which 148 had a rare genetic condition called Tangier disease that caused them to produce very low levels of HDL cholesterol.

The study adjusted for age and other factors that could raise the risk of a heart attack.

To contact the reporter on this story: Shannon Pettypiece in New York at spettypiece@bloomberg.net