A technician at a Merck manufacturing plant performs a quality check on a batch of Vioxx, one of two arthritis drugs that slightly increased the risk of blood clots in a new analysis. Popular arthritis drugs linked to heart attacks But critics say the analysis is flawed, no cause for alarm MSNBC NEWS SERVICES http://www.msnbc.com/news/617196.asp Aug. 21, 2001 ­ The popular and heavily promoted new arthritis drugs Vioxx and Celebrex have been linked by researchers to a small but troubling increase in the risk of blood clots that can lead to heart attacks and strokes. Critics say the analysis is flawed and no cause for alarm. ëIt1s inappropriate at this point to rush to a conclusion that these drugs pose a serious cardiovascular risk.1 ­ DR. THOMAS SCHNITZER Northwestern University STILL, many agree the issue needs to be studied because millions of people take the drugs, known as cox-2 inhibitors. The researchers analyzed four studies that were not designed to examine the drugs1 effects on the heart. Until such research is done, doctors should use caution in prescribing them to patients with heart disease, said Dr. Eric Topol, co-author of the analysis and chairman of cardiovascular medicine at the Cleveland Clinic. Topol said he uses such medication himself for knee arthritis, 3but if I had known heart disease, I would be concerned.2 The analysis, published in this week1s Journal of the American Medicine, included a study that looked at the gastrointestinal side effects in 8,076 patients taking Vioxx or the pain reliever naproxen. Vioxx patients faced double the risk of serious cardiovascular problems, including strokes and heart attacks, though only 111 Vioxx patients had them. Two smaller Vioxx studies also suggested potential heart problems, Topol said. Also, a study of 7,968 patients using Celebrex or two other pain relievers showed a slight but statistically insignificant increase in cardiovascular side effects with Celebrex, but the numbers were 3trending in the wrong direction,2 Topol said. An advisory panel warned the Food and Drug Administration in February of the Vioxx-naproxen study and said Vioxx should carry a warning label about potential cardiovascular risks. The FDA has not yet ruled on that recommendation. Last month Britain1s watchdog National Institute for Clinical Excellence said Celebrex, Vioxx and similar drugs should be limited to high-risk patients, not for safety reasons but on cost effectiveness grounds. It said high-risk patients would be those over 65 and people who suffer stomach problems from traditional anti- inflammatory drugs. The drugs were developed to fight often disabling arthritis inflammation without the stomach problems that can accompany aspirin and other anti-inflammatory drugs. Called COX-2 inhibitors, they block an enzyme of that name that interferes with the production of chemical messengers that cause the pain and swelling of inflammation. But, the study said, the drugs may also promote the formation of clots in blood vessels by decreasing production of a compound that promotes the widening of those vessels. Among the most popular medicines worldwide, they are expected to generate $6 billion in sales and 200 million prescriptions in the United States alone this year, Topol said. Celebrex and Vioxx are widely advertised on television and in magazines. ëMISLEADING DATA1 Skeptics said the researchers presented incomplete and misleading data. 3It1s inappropriate at this point to rush to a conclusion that these drugs pose a serious cardiovascular risk,2 said Dr. Thomas Schnitzer, a Northwestern University rheumatologist. The analysis 3is very far from proof.2 Vioxx manufacturer Merck & Co. and Pharmacia Corp., which makes Celebrex, disputed the analysis and said their drugs are safe. Dr. Laura Demopoulous, Merck1s senior director of cardiovascular clinical research, noted that the Vioxx study involved patients with rheumatoid arthritis, a disease that raises the risk of heart trouble. She also said the results may reflect naproxen1s potential heart- friendly benefits rather than any negative effects from Vioxx. Dr. Steve Geis, Pharmacia vice president for clinical research, said comparing studies involving different drugs and patients with different types of arthritis 3is misleading and it is not quite accurate.2 Dr. John Klippel, medical director for the Arthritis Foundation, said some of the studies included patients taking aspirin, which can benefit the heart by thinning the blood. Still, Klippel said the analysis raises important questions. 3We have to reassure people that these drugs are safe, yet there does seem to be some caution, particularly for people who are at increased risk of cardiovascular disease,2 he said. Dr. Leslie Crofford, a University of Michigan rheumatologist, said the analysis will force doctors to consider such issues when prescribing arthritis medication. While the new drugs might be better for patients at risk for gastrointestinal problems, 3there1s absolutely no data that these drugs are better for arthritis than traditional2 pain relievers, she said. 3They1re good drugs, and for the right people, they can make a big difference. But they1re not for everybody.2 3The report reminds us once again that all drugs have both benefits and risks,2 added Steven Nissen, a co-author of the study. The Associated Press and Reuters contributed to this report.