NEW YORK (AP) - A new study has linked pain killers Vioxx, Celebrex and Bextra to increased cardiovascular risk, reinforcing findings of other trials that have already sparked concern over the safety of a popular category of drugs.

Vioxx and Celebrex increased patients' risk of heart attack and stroke by about 20 per cent while Bextra increased the risk by 50 per cent, according to a study by WellPoint Inc., the largest U.S. provider of health benefits which is based in Indianapolis.

Dr. Sam Nussbaum, WellPoint's executive vice-president and chief medical officer, said Monday the study is further evidence of an "increasingly compelling trend" of data that show the drugs elevate patients' risk of heart attack and stroke.

Later this week the U.S. Food and Drug Administration is holding hearings on the safety of the class of drugs known as Cox-2 inhibitors. Merck & Co. removed Vioxx from the market last year after a study showed it doubled patients' risk of heart attack and strokes.

Pfizer Inc. makes Bextra and Celebrex, which remain on the market.

WellPoint studied the records of 7,232 patients over the age of 40 taking one of the three drugs and compared them with records of 629,245 people older than the age of 40 who were not taking any of the drugs. WellPoint shared the data with researchers at the University of Indiana's medical school, who adjusted the information for heart attack and stroke risk factors, such as age.

WellPoint began the study after Vioxx was removed from the market. It examined patient records from January 2001 through June 30, 2004. All the patients were on the drugs for at least 18 months. Merck officials have insisted the problems with Vioxx didn't become apparent until patients were taking the drug for at least that long.

Drug companies have criticized studies that retrospectively examine patient records, saying the gold standard of drug trials is a blind, placebo-controlled study.

But Nussbaum defended the practice.

"This is how drugs are used in the real world," said Nussbaum. "It is an important and sound analysis."

Nussbaum said WellPoint had shared the data with the FDA as well as Merck and Pfizer.

Pfizer spokeswoman Mariann Caprino said the company had been given the study results, but had not seen all the data or the methodology. She added the WellPoint report did not change the preponderance of peer-reviewed, scientific studies that support Celebrex's safety. Pfizer has previously said a review of its internal studies did not show that either Celebrex or Bextra increased patients' risk for cardiovascular problems.

A Merck spokeswoman couldn't find anyone aware of the study. The FDA didn't return calls.

Nussbaum said WellPoint's study had not caused it to alter its policy of requiring doctors to receive prior authorization before prescribing Bextra or Celebrex. He said that was because the FDA had approved the drugs.

WellPoint's policy could change depending on the outcome of the FDA hearing. Recently, health maintenance organization Kaiser Permanente told its doctors to stop prescribing Bextra.

Dr. Eric Matteson. a professor of medicine in the division of rheumatology at the Mayo Clinic in Rochester, Minn. said the study was significant because of the amount of patients it included and because it backs up other studies.

"All the signals are pointing in the same direction," Matteson said.

There have been two studies linking Bextra to increased risk of heart attack and strokes while two separate trials indicated Celebrex elevates the likelihood of cardiovascular problems.

Matteson doesn't expect the FDA to remove Bextra and Celebrex from the market. Cox-2 inhibitors were developed to be reduce the risk of gastrointestinal problems associated with older pain relievers such as naproxen. However, unlike Vioxx, neither Celebrex or Bextra can say on their labels that they reduce gastrointestinal problems.

Matteson said there is anecdotal evidence of their benefit.

He said he would not be surprised if the FDA demands that Pfizer put a "black box" warning on Celebrex's label to highlight the cardiovascular risk. That is the agency's most severe warning.

Bextra already has a black box warning.

"Clearly there is a degree of risk in these drugs and doctors need to be more careful about prescribing them," said Matteson.

Pfizer shares closed up 33 cents, or 1.3 per cent, to $25.48 US on the New York Stock Exchange Monday. Merck shares gained 20 cents to $29.41