updated 11/5/2007 3:40:53 PM ET 2007-11-05T20:40:53

Researchers involved in a study that prompted Pfizer Inc. to halt development of torcetrapib, a drug designed to boost "good" cholesterol levels, said Monday that they can't explain exactly how the drug contributed to an increase in cardiovascular problems and death.

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In December, Pfizer halted the development of torcetrapib on a recommendation by the independent board overseeing the study, which found an increase in deaths and cardiovascular problems among patients receiving torcetrapib. Complete results from the trial, known as Illuminate, are scheduled to be presented Monday at the American Heart Association's annual meeting in Orlando and are being published in the New England Journal of Medicine.

Questions remain, however, about whether the deaths and heart problems are unique to Pfizer's torcetrapib or apply to the drug class as a whole.

Torcetrapib falls into a proposed class of drugs known as inhibitors of cholesteryl ester transfer protein, or CETP, which are designed to raise the level of good cholesterol in the blood. It's thought that boosting "good" cholesterol while lowering "bad" cholesterol with statin drugs could better reduce risks for heart attacks and strokes.

The study, led by researchers at the Heart Research Institute in Sydney, involved 15,067 patients who were considered at high risk of cardiovascular problems like heart attacks and strokes. All the patients received atorvastatin, a cholesterol-lowering drug Pfizer sells under the brand name Lipitor, while half received Lipitor and torcetrapib.

After a year, the study showed a 58 percent increase in the risk of death among patients in the torcetrapib group and a 25 percent increase in the risk of cardiovascular problems such as heart attacks, compared with those receiving Lipitor alone. In all, 93 patients taking torcetrapib died, compared with 59 taking only Lipitor.

Torcetrapib boosted so-called good cholesterol, or HDL, by an average of 72.1 percent and lowered "bad" LDL cholesterol by 24.9 percent.

The study showed torcetrapib boosted blood pressure, a side effect seen in earlier studies. But researchers said many of the deaths in the torcetrapib group had blood-pressure levels lower than the median blood pressure level among patients in the study.

Dr. Philip Barter, lead researcher with the Heart Research Institute, said the most plausible explanation for the increase in deaths and cardiovascular problems is that torcetrapib increased aldosterone levels, a hormone involved in blood-pressure regulation. But, he said, more research is needed to explain how the aldosterone rise may have contributed to the safety problems with torcetrapib.

Barter said that while the study cannot rule out a problem from inhibiting CETP itself, he hoped research on other compounds in the same drug class moves forward.

Merck & Co. and Roche Holdings AG are developing CEPT inhibitors but have been partly waiting for the results of the Illuminate trial before deciding to move forward with further development of the drugs. Pfizer also has two other CETP-inhibitor compounds in early stages of development. All the companies are looking for answers as to whether any drug that inhibits CETP would have the effects found in the study.

"There are many questions that still remain," said Steve Ryder, Pfizer's head of torcetrapib research and development.

Researchers from Merck are scheduled to present a paper at AHA on torcetrapib and its own compound, anacetrapib, in animal studies that shows torcetrapib boosted blood pressure as well as aldosterone while the same increase wasn't found with anacetrapib.

Daniel Bloomfield, Merck's senior director of cardiovascular research, said the company still hasn't decided if it's moving forward with development of anacetrapib. So far in human studies, the drug hasn't been linked to increases in blood pressure.

Copyright 2007 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


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