One report from Brigham and Women's Hospital, and Harvard Medical School, Boston, said an analysis of 114 studies involving more than 116,000 people showed that rofecoxib (the drug sold as Vioxx) "was associated with increased renal and (heart) arrhythmia risks."

Why the drug would cause kidney damage is unclear, it added.

Merck & Co Inc. withdrew Vioxx from the market in September 2004 after a three-year study showed it doubled the risk of heart attack and strokes in patients taking it for at least 18 months.

A second report from the University of Newcastle, New South Wales, Australia, said a look at 23 studies confirms the findings of an increased risk of heart problems with Vioxx that could be found "during the first 30 days of treatment. This conclusion is consistent with a recent reanalysis ... which contradicts the original suggestion that the vascular risk was only seen after 18 months."

Merck, facing more than 11,500 product liability lawsuits from people claiming to have been harmed by Vioxx, has said it still believes the data confirm the increased heart risk begins only after the medicine had been taken for 18 months.

The Australian analysis also said it found that celecoxib -- sold as Celebrex by Pfizer Inc. -- was not associated with heart problems at a dose no greater than 200 milligrams a day.

It also said that its review "raises serious questions about the safety of diclofenac, an older (analgesic) drug" which is sold more in Europe than the United States.

"In conclusion ... diclofenac seems to share this risk and, unlike celecoxib, it appears to be harmful at commonly used doses. We believe there are grounds for reviewing its regulatory status," the report added.

The studies were published in this week's Journal of the American Medical Association along with an editorial from David Graham, a physician who works for the U.S. Food and Drug Administration but whose comments were labeled as his own views and not those of the regulatory agency.

"What does this all mean? First, rofecoxib (Vioxx) increases the risk of acute myocardial infarction at low and high doses," he said. "There is no initial 18-month period of immunity from risk."

He said Celebrex "also increases (heart) risk at doses higher than 200 mg/d ... several other NSAIDs (non-steroidal anti-inflammatory drugs) increase risk, including ... diclofenac and meloxicam ... indomethacin and probably ibuprofen," while studies agree that naproxen is "neutral" for heart attack risk.

Graham added that for most patients with arthritis or other conditions requiring chronic pain relief "naproxen appears to be the safest NSAID choice from a cardiovascular perspective." Naproxen is commonly sold as Aleve by Bayer Corp.