-->COX-2 Inhibitors May Increase Cardiovascular Risk
COX-2 inhibitors have been marketed as anti-inflammatory agents that do not have gastric toxicity. Concerns about their prothrombotic effects prompted these investigators to analyze data from 2 randomized trials of COX-2 inhibitors (VIGOR and CLASS) and from 2 very small trials submitted to the FDA. None of the 4 trials focused on cardiovascular risk.
VIGOR compared rofecoxib and naproxen in 8076 patients with rheumatoid arthritis (RA). The 9-month rate of adverse cardiovascular events was significantly higher in the rofecoxib group than in the naproxen group (odds ratio, 2.38). However, in CLASS -- which compared celecoxib, ibuprofen, and diclofenac in 8059 patients with RA or osteoarthritis (OA) -- 6-month rates of adverse cardiovascular events did not differ significantly among the groups.

Taken together, the 2 trials submitted to the FDA (both of rofecoxib vs. nabumetone vs. placebo for OA of the knee) yielded mixed results. An additional review of the FDA's adverse-event reporting system yielded about 100 cases of thrombotic or embolic events attributable to each of rofecoxib and celecoxib.

Finally, the researchers compared MI rates among recipients of COX-2 inhibitors in VIGOR and CLASS with MI rates among more than 20,000 placebo recipients in a meta-analysis of 2 large trials of aspirin versus placebo. Rates were significantly higher among recipients of COX-2 inhibitors.

Comment: These results raise important questions about COX-2 inhibitors' potential cardiovascular risks. However, although the present analysis was conducted well, the study populations' heterogeneity, the lack of prespecified endpoints, and the problems inherent to retrospective analysis make drawing firm conclusions difficult. Until a prospective randomized trial directly addresses the cardiovascular risks of COX-2 inhibitors, clinicians should exercise caution in prescribing them to at-risk patients.

— JM Foody


Published in Journal Watch Cardiology October 12, 2001