A trial showing that AstraZeneca Plc's Crestor cholesterol pill prevented heart disease in seemingly healthy people was flawed and may have been biased because of the company's role in the research, according to an article in the Archives of Internal Medicine.

Nine of the 14 researchers who conducted the study, dubbed Jupiter, had financial ties to London-based AstraZeneca that may have influenced the way they did their job, doctors led by Michel de Lorgeril wrote in the report published today. The lead Jupiter researcher is a co-holder of a patent on a protein marker of inflammation that would potentially boost royalties from wider use of Crestor, the authors said.

"The possibility that bias entered the study is particularly concerning because of the strong commercial interest in the study," wrote de Lorgeril of the Universite Joseph Fourier and National Center for Scientific Research in Grenoble, France.

Over five years, using Crestor in people with normal cholesterol may prevent 250,000 heart complications in the U.S., AstraZeneca's researchers said when presenting Jupiter findings at the American Heart Association meeting in 2008. AstraZeneca in March 2008 stopped the study early because of "unequivocal" evidence that the pill cut deaths better than a placebo in people who had no evidence of existing heart disease.

U.S. and European regulators this year allowed the drugmaker to broaden Crestor's use to anyone at an increased risk for heart disease, even if so-called bad cholesterol levels are normal. Crestor belongs to a family of drugs known as statins that work by blocking an enzyme in the liver involved in cholesterol production.

Trial Halt

The results of the 17,802-patient Jupiter study are an exception among 12 other failed cholesterol-lowering research projects, fueling concern that the decision to stop the trial early was faulty, the authors of the Archives article wrote.

"Inconsistencies" in the data "should have led to the continuation of the trial rather than its premature ending," the authors wrote.

Paul Ridker of Harvard Medical School, who led the Jupiter study, said in an e-mail, "My conflict has been publicly disclosed literally hundreds of times going as far back as 1997. There is nothing new here."

The study showed "overwhelmingly" that statin therapy cut the risk of heart disease among people who had high levels of C- reactive protein or CRP, even though their dangerous cholesterol was normal, Ridker said. The U.S. Food and Drug Administration "found the study to have been exceptionally well conducted and without issue" after reviewing the trial data, he wrote.

CRP is a measure of inflammation, and high amounts may mean a risk of heart disease.

Crestor Sales

"Jupiter was undertaken with a fully independent steering committee, data and safety monitoring board, and academic study statistician," Chris Sampson, a spokesman for AstraZeneca, said in an e-mail. "The trial was financially supported by AstraZeneca, but AstraZeneca played no role in conducting data analyses and had no access to unblinded trial data."

Crestor sales probably will rise 68 percent to $7.57 billion by 2012, helped by additional revenue from expanded use on the back of the Jupiter results, according to Gbola Amusa, an analyst for UBS AG in London. The drug is AstraZeneca's third best seller, bringing in $4.5 billion in 2009.

The new expanded indication differentiates Crestor from other cholesterol-lowering medicines and may convince doctors that it's worth the extra cost after Pfizer Inc.'s competing Lipitor pill, the world's best-selling drug, is threatened by generic copies in 2011.

Well Respected

The study investigators are among the most well-respected physician researchers in the world, said Steven Nissen, head of cardiology at the Cleveland Clinic in Ohio. While the benefits of statins in preventing heart disease can be debated, attacking the integrity of the researchers and their work is unhelpful, he said in a telephone interview.

"Jupiter was a meticulously performed trial," he said in a telephone interview. "I trust that they did their job well and the data in Jupiter are presented accurately. I don't think that impugning the integrity of physicians who are well respected serves the scientific world very well."

With assistance from Michelle Fay Cortez in London. Editors: Phil Serafino, Andrew Pollack