| STUDY |
Do COX-2 inhibitors compromise cardiovascular safety? JAMA study points to possible increases in prothrombic activity from use of the drugs. But pharmacist-experts say results are inconclusive, large-scale trial needed. Researchers with the Cleveland Clinic Foundation found that COX-2 inhibitors - the popular painkillers celecoxib; and rofecoxib - may slightly increase a person's risk of stroke, myocardial infarction, or death. The findings were published in the August 22 issue of JAMA. Since COX-2 inhibitors were first marketed in 1999, the agents have been used by millions in the United States and around the world. While the data presented in JAMA indicate a potential problem, experts say the study is far from conclusive and that more trials are needed to test whether use of COX-2 inhibitors really does increase cardiac events. A closer look at COX-2 inhibitors Although the JAMA authors acknowledge that their work is not definitive, they pointed out that COX-2 antagonists may lead to increased prothrombic activity when used to relieve arthritic and musculoskeletal pain. They reached this conclusion by reanalyzing data from 8,076 non-aspirin-using patients in the Vioxx Gastrointestinal Outcomes Research (VIGOR) study, 8,059 aspirin-using and non-aspirin-using patients in the Celecoxib Long-term Arthritis Safety Study (CLASS), and approximately 2,000 patients in two smaller studies. In the VIGOR study, patients with rheumatoid arthritis were randomly assigned to groups receiving naproxen or rofecoxib to assess the gastrointestinal adverse effects of COX-2 inhibitors. Surprisingly, more than twice as many cardiovascular events occurred among patients in the rofecoxib group than among those taking naproxen. The JAMA authors noted a total of 321 people from the VIGOR study population should have been excluded, because for them aspirin was indicated for a variety of cardiovascular risk factors. The reviewers found that this group of patients might be four times as likely to have a cardiovascular event as those taking naproxen. However, none of these included myocardial infarction. In addition, naproxen's platelet-inhibiting effects might have provided a protective effect that celecoxib lacks, in which case, the observed difference would not be a toxic effect of celecoxib. The review authors reported a higher cardiac risk in patients taking rofecoxib in the VIGOR trial and a significantly higher risk of myocardial infarctions in both studies (0.74% for rofecoxib and 0.80% for celecoxib, compared with 0.52% among primary-prevention patients in a recent meta-analysis). The CLASS study included patients suffering from both osteoarthritis and rheumatoid arthritis. Up to 325mg/day of aspirin for cardiovascular prophylaxis was permitted. The authors found no significant difference in the incidence of cardiovascular event between the celecoxib and NSAID groups in either aspirin or nonaspirin users. JAMA study attacked While evidence seems to indicate that COX-2 inhibitors may indeed cause cardiac events, the data review was harshly criticized for several reasons. Leroy Knodel, PharmD, director of the Drug Information Service at the University of Texas Health Science Center in San Antonio, is concerned that the patient populations were not equivalent. "When you take data from one study and start making comparisons with another study, there are many inherent problems," Knodel explained. "Were the two groups comparable in weight or other risk factors? What if one group had more smokers? The data are just not comparable. It is not fair to lump them together." Some are also skeptical of the JAMA study because it is a reanalysis of previous studies. The primary purpose of the VIGOR and CLASS studies was not to examine the agents' effects on the heart, but to test for gastrointestinal effects resulting from the use of COX-2 inhibitors. Reanalyzing the data retrospectively for an effect that was not anticipated can be fraught with pitfalls. No answers, more questions Although the results of this study are inconclusive, any possible adverse effect must be assessed, given the large number of people taking these medications. "What is needed is a large-scale trial to compare COX-2 and aspirin with COX-2 alone," Arthur Schuna, MS, clinical pharmacy professor at the University of Wisconsin-Madison, told Pharmacy Today. In the meantime, COX-2 inhibitors are very effective at reducing pain and inflammation, and they appear to produce fewer serious gastrointestinal events than NSAIDs. In February, data from these studies were presented to an FDA advisory committee, and FDA continues to review the cardiovascular safety of COX-2 inhibitors. "The perception out there is that we have a problem with these agents," Knodel said. "But I don't think the data from the JAMA article are conclusive at this time. |
| UPDATE | 22.08.2001 |
| AUTHOR | Researchers with the Cleveland Clinic Foundation |
|
Want more information ? Interested in the hidden information ? Click here and do your request. |