Arthritis patients left confused after some popular pain relievers were yanked from the market and others were given labels warning of cardiovascular risks may eventually get some valuable guidance.

The Cleveland Clinic yesterday announced it will direct an international study of 20,000 arthritis patients to determine whether several common drugs used to relieve arthritis pain are safe for people at risk of heart problems.

The study will focus on the drugs Motrin, Advil, Naprosyn, Aleve and Celebrex. Earlier this year, the U.S. Food and Drug Administration directed that those drugs, also known as ibuprofen, naproxen and celecoxib, carry warnings for potential increased risk of heart attack, stroke or gastrointestinal bleeding.

Arthritis patients who have heart disease or are at risk of cardiovascular problems will be randomly assigned to take one of the drugs and monitored for an average of two years. Enrollment will begin next year.

"This is designed to be the definitive trial to determine which of the leading pain-relieving drugs is the safest to take if you have heart disease or are at risk for heart disease," said Dr. Steven Nissen, its lead investigator and medical director of the Cleveland Clinic's Cardiovascular Coordinating Center.

The results, he said, could help reassure a public shaken by concerns over the safety of those and similar drugs, including the painkiller Vioxx.

"Right now, people are confused," he said. "They don't know what to take."

Dr. Larry Hurwitz, a cardiologist associated with West Penn Hospital, said the study could have a huge impact.

"Patients have a very difficult decision: whether to deal with pain of arthritis, which can be very significant, or the potential risk of taking these drugs. It's a question of quality of life versus risk of life," he said.

Vioxx and another drug, Bextra, were pulled from the market last year because of their potential for health risks. Both are so-called Cox-2 inhibitors, which are gentler on the stomach than older pain relievers. That left Celebrex as the only available Cox-2 inhibitor.

Vioxx also has prompted a series of lawsuits against drug manufacturer Merck.

The Cleveland Clinic study is funded by Pfizer, the manufacturer of Celebrex. But Dr. Nissen emphasized that protections were in place to ensure the impartiality of the study.

Cleveland Clinic will run the trial and share data with the National Institutes of Health's National Heart, Lung and Blood Institute, which will appoint a representative to serve on the study's executive committee.

"Essentially, we're putting all results in the public domain," he said. "This is all done because of the need for complete transparency and public confidence."

"With the ongoing fiasco with Vioxx and Merck this is the kind of study that needs to be done," said Dr. Paul Killian, chief rheumatologist at West Penn.

Dr. Kent Kwoh, a rheumatologist at the University of Pittsburgh Medical Center, said some doctors have avoided prescribing these medications altogether for long-term use by patients who have cardiovascular risk factors.

Although the study's findings will be important, Dr. Kwoh said, "it may be hard to get people to enroll in this trial because they're taking possibly an increased risk."

In the meantime, Dr. Kwoh said many doctors have turned to non-pharmaceutical treatments, such as physical therapy, bracing and taping, as well as encouraging patients to lose weight and exercise more.

Dr. Joseph Maroon, a UPMC neurosurgeon and team neurosurgeon for the Pittsburgh Steelers, said he has not prescribed Cox-2 inhibitors, naproxen or ibuprofen for two years because of the health risks.

A better study would look at finding drugs that reduce inflammation without putting patients at risk. "In my opinion they're looking at drugs when they should be looking at natural agents," like glucosamine and chondroitin "that reduce pain," he said.