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Post-myocardial infarction: risk of death linked to COX-2 inhibitors and non-selective NSAIDs

Myocardial infarction survivors taking COX-2-selective (NSAIDs) inhibitors or high dosages of nonselective nonsteroidal antiinflammatory drugs ( NSAIDs ) are at a greater risk of a second myocardial infarction or death.

The study, led by Gunnar H. Gislason, at Gentofte University Hospital, DK-2900 Hellerup, ( Denmark ), is the first to examine the risks from all nonsteroidal antiinflammatory drugs in a selected population of patients after a myocardial infarction.

The selective COX-2 inhibitors and other nonselective nonsteroidal antiinflammatory drugs have been associated with increased cardiovascular risk, but the risk in patients with established cardiovascular disease is unknown.

The researchers have analyzed the risk of rehospitalization for acute myocardial infarction and death related to the use of NSAIDs including selective COX-2 inhibitors in patients with prior myocardial infarction.

All patients with first-time myocardial infarction between 1995 and 2002 as well as all prescription claims for NSAIDs after discharge were identified from nationwide Danish administrative registers. The risk of death and rehospitalization for myocardial infarction associated with the use of selective COX-2 inhibitors and nonselective NSAIDs was studied with the use of multivariable proportional hazards models and case-crossover analysis.

A total of 58 432 patients were discharged alive and included in the study; 9773 experienced rehospitalization for myocardial infarction, and 16 573 died.

A total of 5.2% of patients received Rofecoxib ( Vioxx ), 4.3% Celecoxib ( Celebrex ), 17.5% Ibuprofen ( Brufen ), 10.6% Diclofenac ( Voltaren ), and 12.7% other NSAIDs.

For any use of Rofecoxib, Celecoxib, Ibuprofen, Diclofenac, and other NSAIDs, the hazard ratios for death were 2.80 for Rofecoxib, 2.57 for Celecoxib, 1.50 for Ibuprofen, 2.40 for Diclofenac, and 1.29 for other NSAIDS; there were dose-related increases in risk of death for all of the drugs.

There were trends for increased risk of rehospitalization for myocardial infarction associated with the use of both the selective COX-2 inhibitors and the nonselective NSAIDs.

The authors conclude “ Selective COX-2 inhibitors in all dosages and nonselective NSAIDs in high dosages increase mortality in patients with previous myocardial infarction and should therefore be used with particular caution in these patients. “

Source: Circulation, 2006