Use of a cyclooxygenase-2 inhibitor or other non-steroidal anti-inflammatory drug after a myocardial infarction, especially in high doses, increases risk of death, according to a presentation at the American Heart Association’s Scientific Sessions 2005.

“There is no doubt about the beneficial effects of aspirin among patients after heart attack, which is a cheap and effective treatment ? and the scientific evidence is undeniable,” said Gunnar H. Gislason, MD, lead author and research fellow at Bispebjerg University Hospital in Copenhagen, Denmark.

In recent years, evidence has shown that patients treated with selective cyclooxygenase-2 (COX-2) inhibitors are at increased risk of myocardial infarction and death. This was the first study to look at patients who took the drugs after suffering their first myocardial infarction.

The researchers examined records in the Danish National Patients Registry of 58,432 men and women discharged from the hospital during 1995?2002 after a first acute infarction.

At some point after discharge, a total of 41 percent of patients received diclofenac (6172 patients; 10.6 percent), ibuprofen (10,230; 17.5 percent), or another non-selective nonsteroidal drug (7449 patients; 12.7 percent). Slightly less than 10 percent of patients received rofecoxib (3022 patients; 5.2 percent) or celecoxib (2489 patients; 4.3 percent). There was no breakdown based on whether a patient was also taking aspirin.

Analysis of risk for a second myocardial infarction or death from any cause during the time patients were taking one of the medications were compared with risk for patients who were not taking an agent of that class.

?The hazard ratio, which indicates the risk of dying while taking one of the drugs, compared with a risk of 1.0 for similar patients not taking one of the drugs (patients matched to control for age, gender and other medical conditions), was 5.03 for more than 25 mg/day of rofecoxib, 4.24 for more than 200 mg/day of celecoxib, 3.76 for more than 100 mg/day of diclofenac, 1.96 for more than 1200 mg/day of ibuprofen, and 1.22 for non-specified drugs (not divided by dosage because of high variation within group).
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Lower doses of celecoxib (hazard ratio 1.70) and rofecoxib (2.23) were also associated with a significantly higher risk of death, an association that was not found with lower doses of ibuprofen (hazard ratio 0.66) or diclofenac (0.74).

“The most important thing to recognize is that higher doses give a higher risk of death,” Gislason said.

However, researchers did not find an increased risk of a second myocardial infarction with any of the drugs or dosages. “This really surprised us because we had expected that the risk of recurrent heart attack would be high in this population,” Gislason said.

The research team is analyzing death certificates to see what (if any) causes of death were more common in patients taking the drugs. “We’re looking at both cardiovascular and non-cardiovascular causes of death,” Gislason stated.