MONDAY, (HealthDay News)—People who have survived a first heart attack have a higher risk of dying or having a second heart attack if they are taking non-steroidal anti-inflammatory drugs (NSAIDs), including the newer class called cox-2 inhibitors.

The research detailing these findings appears in the June 20 issue of the journal Circulation, and was first presented at the 2005 meeting of the American Heart Association. The results of the two studies are almost the same, although the latest study shows an even higher correlation between NSAID use and a second heart attack.

“The evidence is accumulating, and it seems that patients who have already had a heart attack are at even more risk than we thought before, and we are talking about short-term treatment,” said study lead author Dr. Gunnar H. Gislason, senior resident at Gentofte University Hospital in Copenhagen, Denmark.

Dr. Mark Fendrick, professor of internal medicine at the University of Michigan School of Medicine and professor of health management and policy at the university’s School of Public Health, added, “This is yet another study adding to the mountain of evidence suggesting that we should be very careful about the use of cox-2 drugs, specifically, and possibly all additional NSAIDs for patients at risk for cardiovascular adverse events.”

NSAIDs are pain relievers, including aspirin, ibuprofen and naproxen, that carry a risk of gastrointestinal bleeding. Cox-2 inhibitors are a specific type of NSAID that do not carry that risk.

Cox-2 inhibitors and NSAIDs have been caught in a prolonged furor since September 2004, when the cox-2 Vioxx was withdrawn from the market due to concerns about cardiovascular safety. Similar concerns were raised about Bextra, another cox-2, then Celebrex, and then naproxen, a traditional NSAID. Bextra was later withdrawn from the market.

A number of studies continue to look at the different risks and benefits of the drugs. This new research is the first to look at patients who took NSAIDs after suffering their first heart attack.

The study authors looked at all patients in Denmark who had survived a first heart attack between 1995 and 2002. Then they cross-referenced this information with all prescription claims for NSAIDs after their hospital discharge. A total of 58,432 patients were included in the study.

Patients who had survived a first heart attack and were taking any NSAID were more likely to die than those who had survived one heart attack and were not taking NSAIDs. Death rates were highest among those taking cox-2 drugs and high doses of traditional NSAIDs.

Compared to patients not taking any of these drugs, the risk of death was two to three times higher for patients taking low-dose (25 milligrams or less a day) of Vioxx (rofecoxib) or 200 milligrams or less a day of Celebrex (celecoxib).

The risk of death was five times higher for patients taking high-dose Vioxx (more than 25 milligrams a day); almost five times as high among those taking more than 200 milligrams of Celebrex; more than four times higher for those on high-dose diclofenac (more than 100 milligrams daily); and more than two times greater for those taking high-dose ibuprofen (more than 1,200 milligrams daily).

Taking NSAIDs for only short periods of time was enough to show a detrimental effect, the study found.

Although aspirin was not evaluated in the study, the authors presumed that more than 90 percent of people being analyzed were probably taking this drug. Aspirin has a proven beneficial effect in preventing heart attacks.

More and more studies, most of them observational, are showing that NSAIDs have this deleterious effect. A large, randomized, controlled trial has yet to be completed, however, although one sponsored by Pfizer and conducted by the Cleveland Clinic will soon be under way.

So what should consumers do?

“Physicians and patients at risk should think thrice, not twice, before using NSAIDs,” Fendrick said. “If someone with a cardiovascular risk absolutely needs NSAIDs, given the available evidence, I would suggest taking naproxen with a proton pump inhibitor” to counteract the gastrointestinal effects.

Gislason added: “Our recommendation is that patients should at least consult their physician if they are taking any of those drugs, and our recommendation would be that if they can’t be without them, they should stick with low doses of the traditional NSAIDs and probably avoid the new cox-2 inhibitors.”

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