Association between nonnaproxen NSAIDs, COX-2 inhibitors and hospitalization for acute myocardial infarction among the elderly: a retrospective cohort study.
OBJECTIVE
To evaluate the association between rofecoxib, celecoxib, diclofenac, and ibuprofen and the risk of hospitalization for acute myocardial infarction (AMI) in an elderly population.


METHODS
We conducted a retrospective cohort study, using data from the government of Quebec health insurance agency databases, among patients 65-80 years of age who filled a prescription for any of the study drugs during 1999-2002. Cox regression models with time-dependent exposure were used to compare the incidence rates of hospitalization for AMI adjusting for patients' baseline characteristics. Analyses stratified by dose and number of supplied days were also conducted.


RESULTS
At the index date, a total of 91 062 patients were taking rofecoxib, 127 928 celecoxib, 49 193 diclofenac, and 15 601 ibuprofen. The adjusted hazard ratio (HR) (95%CI) of hospitalization for AMI were: celecoxib versus rofecoxib: 0.90 (0.79, 1.01); ibuprofen versus rofecoxib: 0.95 (0.65, 1.37); diclofenac versus rofecoxib: 1.01 (0.84, 1.22). In secondary analyses based on intended duration of use, neither COX-2 selective inhibitor was associated with a higher risk than ibuprofen or diclofenac. The unadjusted risk of AMI for all NSAIDs increased with dose. In the direct two way adjusted comparison of each NSAID stratified by dose, the only statistically significant difference was with rofecoxib >25 mg/day versus celecoxib >200 mg/day.


CONCLUSIONS
In this study there was no difference between AMI occurrence in elderly patients taking rofecoxib or celecoxib at recommended doses for chronic indications versus those taking ibuprofen/diclofenac. However, the risk of AMI was higher among patients using higher doses of rofecoxib (>25 mg/day) compared to patients using higher doses of celecoxib (>200 mg/day).
Rahme
Elham
E
Department of Medicine McGill University, and Research Institute, McGill University Health Center, Montreal, Canada. elham.rahme@mcgill.ca
Watson
Douglas J
DJ
Kong
Sheldon X
SX
Toubouti
Youssef
Y
LeLorier
Jacques
J
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000627:therapeutic use*; D000068579:Celecoxib; D015331:Cohort Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004008:Diclofenac / Q000009:adverse effects / Q000627:therapeutic use; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D004363:Drug Utilization / Q000706:statistics & numerical data; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects / Q000627:therapeutic use; D007783:Lactones / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced / Q000453:epidemiology*; D011358:Product Surveillance, Postmarketing / Q000379:methods / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use; D011792:Quebec / Q000453:epidemiology; D012189:Retrospective Studies; D012737:Sex Factors; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D004008:Diclofenac; D000068579:Celecoxib; D007052:Ibuprofen