Study supports NSAID class effect on MI risk: coxibs no more a factor than non-COX-2.(News)

VIENNA -- Although the cy-clooxygenase-2 (COX-2)-selective NSAIDs have acted as lightning rods for recent concern regarding cardiovascular risk, the reality is that many traditional NSAIDs carry as great or even greater associated risks of acute myocardial infarction, Gurkirpal Singh, M.D., reported at the annual European Congress of Rheumatology.

"All the media attention has focused on the COX-2-selective inhibitors as the drugs that cause heart attacks, but when you look at the coxibs compared to noncoxibs--and this is very important--it turns out the coxibs do not cause heart attacks any more than the non-COX-2 drugs, except for rofecoxib (Vioxx), which has a higher rate than all the other noncoxibs. But both celecoxib (Celebrex) and valdecoxib (Bextra) do not seem to increase the risk compared to traditional NSAID therapies," said Dr. Singh of Stanford (Calif.) University.

This was the key finding of his just-completed nested case-control study examining the link between NSAIDs and acute MI in a cohort of 651,000 adults with physician-diagnosed arthritis featuring nearly 2.4 million patient-years of follow-up within the California Medicaid program.

"This is by far the largest study on this issue. In fact, it's larger than all the other studies done so far combined," he noted at the meeting, which was sponsored by the European League Against Rheumatism.

Although the study was presented for the first time at the Vienna meeting, the results are generally supportive of the Food and Drug Administration's decision months earlier that NSAID-associated MI risk is essentially a drug class effect. The FDA will require all NSAIDs sold in the United States, whether by prescription or over the counter, to include a black box warning that any of these drugs may increase the risk of MI.

Dr. Singh's study, commissioned by the FDA and conducted by the Institute of Clinical Outcomes Research and Education, Palo Alto, Calif., included 15,343 arthritis patients with acute MI, each matched with four controls. The key end point was the MI rate in current users of specific NSAIDs compared with the MI rate in patients with remote exposure to any NSAID or in those who never used these drugs.

After adjustment for 39 potential confounders, including concurrent aspirin use, the NSAID that emerged as having the greatest MI risk was indomethacin. ...