COX-2 Inhibitors and Other NSAIDs Increase Mortality in Acute MI Patients

From Medscape Medical News

by Martha Kerr

Nov. 15, 2005 (Dallas) — An analysis of data from a nationwide registry shows that the use of selective cyclooxygenase-2 (COX-2) inhibitors is contraindicated in acute myocardial infarction (MI) patients. The data also show that only low doses of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) should be used in this population, because the drugs work through both the COX-1 and COX-2 pathways.Data on 58,432 patients in the Danish National Patients' Registry discharged from hospitals between 1995 and 2002 after a first MI were presented here by Gunnar H. Gislason, MD, from Bispebjerg University in Copenhagen, Denmark, at the American Heart Association 2005 Scientific Sessions. Patients in the analysis had taken NSAIDs, including COX-2 inhibitors, at least once. Of these, 5.2% had taken rofecoxib, 4.3% celecoxib, 17.5% ibuprofen, 10.6% diclofenac, and 12.7% had taken other NSAIDs. "The treatment time [with NSAIDs] on average was about one month, corresponding to the expectation that these drugs were being used for various sources of pain," Dr. Gislason told Medscape. He and his colleagues reported that all NSAIDs were associated with an increased risk of all-cause mortality, which increased further when higher doses were used. However, NSAIDs, including selective COX-2 inhibitors, did not increase the risk of recurrent MI. "Differences in risk within NSAIDs were as great as between selective COX-2 inhibitors and other NSAIDs," the researchers noted in their study abstract. "There was a trend for slightly elevated risk of recurrent MI associated with the COX-2 inhibitors [hazard ratio, 1.5], but this was not statistically significant," Dr. Gislason announced. "One possible explanation was that the increased mortality was due to the higher occurrence of fatal MIs, which caused patients to die before they reached hospital. We are currently looking at death certificates to explore if there is some specific cause of death more common than another."Hazard ratios for all-cause mortality according to specific NSAIDs included celecoxib at more than 200 mg/day, 4.24; rofecoxib at more than 25 mg/day, 5.03; diclofenac at more than 100 mg/day, 3.76; ibuprofen at more than 1,200 mg/day, 1.96; unspecified NSAIDs, 1.22 (P < .001 for all comparisons)."Since all patients had suffered a previous MI, the majority were taking prophylactic aspirin. Aspirin could therefore play a key role in preventing thrombosis in patients taking NSAIDs or COX-2 inhibitors, but there were other harmful mechanisms of [NSAIDs and COX-2 inhibitors] that increased mortality," Dr. Gislason said.Robert O. Bonow, MD, chief of the division of cardiology at Northwestern Feinberg School of Medicine in Chicago, Illinois, and past president of the American Heart Association, told Medscape that the proven benefits of aspirin after MI may have diluted the adverse effects seen with NSAIDs. "This is a major limitation of the study," he pointed out.Dr. Gislason said that "patients who suffer from MI are in an age class where rheumatic problems are common and an indication for an NSAID [or a COX-2 inhibitor] is often present. With the results of the current study, the advice to post-MI patients should be to not use COX-2 inhibitors and use NSAIDs only at low doses.""Physicians should discuss the risks involved with these drugs with their patients," Dr. Bonow advised. "You need to evaluate the risks of NSAIDs for high-risk heart patients against their benefits. For instance, being active is good for the heart, and NSAIDs may facilitate exercise."AHA 2005 Scientific Sessions: Abstract 1838. Presented Nov. 13, 2005.