HDL Cholesterol May Not Help The Heart After All
The good cholesterol that scientists have thought helped unclog arteries had no effect on heart disease in a study published today in the Journal of the American Medical Association, casting doubt on a theory drugmakers have spent more than $1 billion pursuing, Bloomberg News writes.
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, throwing into question the notion that raising HDL helps reduce plaque in arteries, a theory Pfizer, Merck and Roche have all pursued at various times, the wire notes.
“There is really no evidence that this method is going to work,” Anne Tybjaerg-Hansen, a study and clinical biochemistry researcher at Copenhagen University Hospital, tells Bloomberg. “This theory has been around for a long time, but this study just doesn’t support it.” The reason may be that other HDL research examined patients with high levels of triglycerides, not low HDL levels, may have caused their increased heart risk, she adds. Here is the abstract.
This may explain why torcetrapib, which Pfizer spent more than $1 billion developing, raised HDL levels without providing heart benefits, according to the study. Analysts had expected torcetrapib would have more than $14 billion in annual sales, but Pfizer halted development in 2006 due to increased deaths. Meanwhile, Merck and Roche continue to develop drugs that raise HDL.
Yale Mitchel, Merck’s vp of cardiovascular disease research, says the study, which was small and in a rare patient population, won’t persuade the drugmaker to change its plans, 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, Bloomberg writes, adding that the drug is in the third and final stage of testing necessary to gain regulatory approval.
“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,” Mitchel tells Bloomberg. “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’s HDL research is temporarily on hold, while Roche’s drug is in the final stages of testing and it will file for FDA 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,” a Roche spokesman tells Bloomberg.
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 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.