The analysis casts doubt on whether Merck's Arcoxia can be a safe option for patients, medical and regulatory experts said. The report suggests that the medicine, designed as a successor pill to Vioxx, may not gain U.S. Food and Drug Administration clearance, doctors said.

``Finding out that Arcoxia is no worse than diclofenac does not mean that it is approvable,'' said Steven Nissen, the chairman of the cardiology department at the Cleveland Clinic and president of the American College of Cardiology. ``I would argue that it is not approvable and I think the FDA will not approve it.''

Merck, which is facing more than 16,000 lawsuits related to Vioxx, is seeking FDA approval of Arcoxia two years after the agency rejected the drug's application in October 2004, citing a need for more safety data.

Shares of Merck fell $1.07, or 2.5 percent, to $41.08 at 9:31 a.m. in New York Stock Exchange composite trading.

Results

The analysis of data from medical databases including more than 1.5 million patients showed that Vioxx increased cardiovascular disease risk by about 35 percent. Diclofenac use produced about a 40 percent greater risk.

``My conclusion is Arcoxia increases the risk of heart attack and stroke and from that perspective it is no different from Vioxx,'' David Graham, an FDA official who has been critical of the agency's handling of Vioxx, said in an interview. ``If I were part of the decision-making process I wouldn't approve it based on this study.''

In an editorial accompanying the published report, Graham criticized Merck's intentions to seek marketing clearance of Arcoxia and its study which showed the drug had no greater risk of heart attack and stroke than diclofenac.

The study's design is ``well-known to be especially poor at identifying differences in safety risks between drugs, thereby stacking the deck in favor of its drug,'' Graham wrote.

Merck has submitted the data to the FDA and European Union regulators, which monitor the safety of painkillers. Arcoxia is already sold in 62 countries in Europe, Latin America and Asia.

Cox-2

Arcoxia and Vioxx are from a group of pain medicines called Cox-2 inhibitors. The drugs, which also include Pfizer Inc.'s Celebrex, were developed in the 1990s as a safer alternative to older painkillers that can cause stomach bleeding, such as naproxen and diclofenac.

The medicines target the production of the Cox-2 enzyme linked to pain and swelling while sparing the Cox-1 enzyme that protects the stomach from its own acid.

All new applications for approval of Cox-2 inhibitors should include research comparing the drug to naproxen, which is shown in the studies to have a neutral impact on the heart, Nissen said. There is no study comparing Arcoxia to naproxen, and it's unlikely that Merck will undertake one now, he said.

To optimize safety, Arcoxia should be compared with naproxen given with an anti-ulcer medication known as a proton pump inhibitor, Graham said.

Merck Response

Merck chose to compare Arcoxia with diclofenac because the latter is a popular anti-inflammatory drug ``used three times more than naproxen,'' said Merck spokesman Christopher Loder said in an e-mailed statement

Chris Cannon, a cardiologist at Brigham and Women's Hospital in Boston and co-chairman of the steering committee overseeing the study comparing Arcoxia and diclofenac said detailed findings will be presented at the meeting of the American Heart Association in November.