Clinical

Lumiracoxib use linked with low GI risk

Last Updated: 2004-08-19 18:30:04 -0400 (Reuters Health)

By Karla Gale

NEW YORK (Reuters Health) - While the incidence of serious cardiovascular events is not significantly different with lumiracoxib compared with other nonsteroidal anti-inflammatory agents (NSAIDs), the cyclo-oxygenase 2 selective inhibitor is associated with a three- to four-fold reduction in ulcer complications, according to study findings published in the August 21st issue of The Lancet.

The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) study enrolled 18,325 patients 50 years or older with osteoarthritis, who were randomly assigned to lumiracoxib 400 mg once daily (n = 9156), naproxen 500 mg twice daily (n = 4754) or ibuprofen 800 mg three times daily (n = 4415).

Patients at cardiovascular risk were not excluded, lead author Dr. Michael E. Farkouh, of New York University School of Medicine, told Reuters Health. "We only excluded people who had a cardiovascular event within the previous 6 months," he explained. "If they had an MI, a stroke, or bypass surgery more than 6 months before, they were eligible for the study, but they were on low-dose aspirin."

"The primary endpoint, including the incidence of myocardial infarction, did not differ between lumiracoxib and either ibuprofen or naproxen," the researchers report.

Patients taking lumiracoxib had significantly smaller mean changes from baseline in systolic and diastolic blood pressure compared with NSAIDs, which in the long-run could translate into a greater clinical cardiovascular benefit, the authors maintain.

In patients not taking low-dose aspirin, the rate of ulcer complications was 0.25% in the lumiracoxib group and 1.09% in the NSAID group (p < 0.0001). Among those taking low-dose aspirin, however, differences between groups were not significant.

The proportion of patients with transaminase levels more than three times the upper limit of normal was 2.57% in the lumiracoxib group and 0.63% in the NSAID group (p < 0.0001). These abnormalities resolved when the drugs were discontinued.

"Liver function should be monitored routinely," Dr. Farkouh emphasized, "especially since patients are often on other drugs as well.

The decision to use lumiracoxib or another NSAID "should be based on economics, on patient preference, and on the patient's prior history," he continued. "If the risk is great enough of an ulcer, I think it's safe to use lumiracoxib from a cardiac perspective. But if they don't have any stomach problems, you might favor naproxen."

Not everyone agrees, however, that lumiracoxib is associated with a salutary risk-benefit profile. In an editorial, Drs. Eric J. Topol and Gary W. Falk, at Cleveland Clinic Foundation in Ohio, point out that while not statistically significant, there was a higher MI rate with lumiracoxib than with naproxen, at 0.38% and 0.21%, respectively.

The findings "reinforce the concept that naproxen provides some anti-thrombotic protective effect, but do not clearly exonerate [lumiracoxib] or other coxibs from potentiating myocardial infarctions," they write.

Lancet 2004;364:639-640,665-684.