Effect of selective cyclooxygenase 2 inhibitors and naproxen on short-term risk of acute myocardial infarction in the elderly.
BACKGROUND
Recent debate has emerged regarding the cardiovascular safety of selective cyclooxygenase 2 inhibitors and the possible cardioprotective effect of naproxen sodium. We compared the rates of acute myocardial infarction (AMI) among elderly patients dispensed selective cyclooxygenase 2 inhibitors, naproxen, and nonselective nonnaproxen nonsteroidal anti-inflammatory drugs (NSAIDs).


METHODS
We conducted a population-based retrospective cohort study using administrative health care data from Ontario, Canada, from April 1, 1998, to March 31, 2001. We identified NSAID-naive cohorts of subjects aged 66 years and older in whom treatment was initiated with celecoxib (n = 15 271), rofecoxib (n = 12 156), naproxen (n = 5669), and nonnaproxen nonselective NSAIDs (n = 33 868), along with a randomly selected control cohort not exposed to NSAIDs (n = 100 000). Multivariate Cox proportional hazards models were used to compare AMI rates between study drug groups while controlling for potential confounders.


RESULTS
Relative to control subjects, the multivariate model showed no significant differences in AMI risk for new users of celecoxib (adjusted rate ratio [aRR], 0.9; 95% confidence interval [CI], 0.7-1.2), rofecoxib (aRR, 1.0; 95% CI, 0.8-1.4), naproxen (aRR, 1.0; 95% CI, 0.6-1.7), or nonnaproxen nonselective NSAIDs (aRR, 1.2; 95% CI, 0.9-1.4).


CONCLUSIONS
The findings of this observational study suggest no increase in the short-term risk of AMI among users of selective cyclooxygenase 2 inhibitors as commonly used in clinical practice. Furthermore, the findings do not support a short-term reduced risk of AMI with naproxen.
Mamdani
Muhammad
M
Institute for Clinical Evaluative Sciences, 2075 Bayview Ave-G215, Toronto, Ontario, Canada M4N 3M5. muhammad.mamdani@ices.on.ca
Rochon
Paula
P
Juurlink
David N
DN
Anderson
Geoffrey M
GM
Kopp
Alex
A
Naglie
Gary
G
Austin
Peter C
PC
Laupacis
Andreas
A
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007783:Lactones / Q000009:adverse effects; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D009288:Naproxen / Q000009:adverse effects*; D009864:Ontario / Q000453:epidemiology; D016016:Proportional Hazards Models; D011720:Pyrazoles; D012189:Retrospective Studies; D012307:Risk Factors; D013449:Sulfonamides / Q000009:adverse effects; D013450:Sulfones
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen; D000068579:Celecoxib