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Investigational COX-2 inhibitor etoricoxib comparable to diclofenac in cardiovascular safety

A comparison of the investigational COX-2 inhibitor etoricoxib and diclofenac found no increase in the risk of cardiovascular events over 3 years with etoricoxib.

A comparison of the investigational COX-2 inhibitor etoricoxib and diclofenac found no increase in the risk of cardiovascular events over 3 years with etoricoxib.

The finding suggests that "COX-2 selectivity alone does not increase cardiovascular risk," said Christopher Cannon, MD, lead investigator of the Multinational Etoricoxib and Diclofenac Arthritis Long-Term (MEDAL) study. Dr. Cannon reported the results of the study yesterday at the American Heart Association (AHA) Scientific Sessions in Chicago.

In MEDAL, 34,701 patients aged 50 years or older with osteoarthritis or rheumatoid arthritis were randomized to 60 or 90 mg/d of etoricoxib or 150 mg/d (50 mg 3 times daily or 75 mg twice daily) of diclofenac. The mean duration of therapy was 18 months.

At 3 years, there were 320 thrombotic cardiovascular events in the group randomized to etoricoxib and 323 in those randomized to diclofenac, a nonsignificant difference. The rate of fatal thrombotic cardiovascular events was 0.17 per 100 patient-years in each group.

Etoricoxib did significantly reduce the rate of upper gastrointestinal events by 31%, but the incidence of perforations was not different between etoricoxib and diclofenac.

A meta-analysis published last month in the Journal of the American Medical Association (JAMA) found that diclofenac was associated with the highest risk of cardiovascular events among the older nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Diclofenac has more selectivity for COX-2 than ibuprofen, aspirin, or naproxen. Dr. Cannon, associate professor of medicine at Harvard Medical School, Boston, Mass., noted that the meta-analysis was a compilation of observational studies, whereas MEDAL provides data from a randomized, controlled study directly comparing 2 agents.

Although congestive heart failure was rare, it occurred more often in the group receiving 90 mg/d of etoricoxib compared with diclofenac, although this difference was not significant. Discontinuation for edema was also greater with 90 mg/d of etoricoxib than with diclofenac, but the rates were similar for 60 mg/d of etoricoxib and diclofenac. Both doses of etoricoxib were associated with higher rates of discontinuation due to increases in blood pressure compared with diclofenac.

"We're moving into an era where we do have choices and probably should be thinking about different agents for different patients," Dr. Cannon said. Direct comparisons of COX-2 inhibitors with ibuprofen and naproxen are needed, he said.

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© Mathematica - The Commonwealth Fund
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