Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction

• Published in: Circulation (New York, N.Y.) Vol. 113; no. 25; pp. 2906 - 2913
• Main Authors: GISLASON, Gunnar H, JACOBSEN, Søren, TORP-PEDERSEN, Christian, RASMUSSEN, Jeppe N, RASMUSSEN, Søren, BUCH, Pernille, FRIBERG, Jens, SCHRAMM, Tina Ken, ABILDSTROM, Steen Z, KØBER, Lars, MADSEN, Mette
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 27-06-2006
• Subjects: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal - adverse effects; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Celecoxib; Confidence Intervals; Coronary heart disease; Cross-Over Studies; Cyclooxygenase 2 Inhibitors - adverse effects; Cyclooxygenase 2 Inhibitors - therapeutic use; Denmark; Diclofenac - adverse effects; Diclofenac - therapeutic use; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Dose-Response Relationship, Drug; Female; Heart; Humans; Ibuprofen - adverse effects; Ibuprofen - therapeutic use; Lactones - adverse effects; Lactones - therapeutic use; Male; Medical sciences; Middle Aged; Multivariate Analysis; Myocardial Infarction - drug therapy; Myocardial Infarction - mortality; Neurology; Odds Ratio; Patient Readmission; Proportional Hazards Models; Pyrazoles - adverse effects; Pyrazoles - therapeutic use; Recurrence; Registries; Retrospective Studies; Risk Factors; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Sulfones - adverse effects; Sulfones - therapeutic use; Vascular diseases and vascular malformations of the nervous system; Denmark; Myocardial infarction; drugs; Heart disease; Mortality; Antiinflammatory agent; Risk factor; nonsteroidal antiinflammatory drugs; Cardiovascular disease; Cyclooxygenase 2 inhibitor; Myocardial disease; cyclooxygenase-2 inhibitors
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.106.616219

The selective cyclooxygenase-2 (COX-2) inhibitors and other nonselective nonsteroidal antiinflammatory drugs (NSAIDs) have been associated with increased cardiovascular risk, but the risk in patients with established cardiovascular disease is unknown. We analyzed the risk of rehospitalization for acute myocardial infarction (MI) and death related to the use of NSAIDs including selective COX-2 inhibitors in patients with prior MI.
All patients with first-time MI 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 MI 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 MI, and 16 573 died. A total of 5.2% of patients received rofecoxib, 4.3% celecoxib, 17.5% ibuprofen, 10.6% diclofenac, and 12.7% other NSAIDs. For any use of rofecoxib, celecoxib, ibuprofen, diclofenac, and other NSAIDs, the hazard ratios and 95% confidence intervals for death were 2.80 (2.41 to 3.25; for rofecoxib), 2.57 (2.15 to 3.08; for celecoxib), 1.50 (1.36 to 1.67; for ibuprofen), 2.40 (2.09 to 2.80; for diclofenac), and 1.29 (1.16 to 1.43; 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 MI associated with the use of both the selective COX-2 inhibitors and the nonselective NSAIDs.
Selective COX-2 inhibitors in all dosages and nonselective NSAIDs in high dosages increase mortality in patients with previous MI and should therefore be used with particular caution in these patients.