Patients exposed to rofecoxib and celecoxib have different odds of nonfatal myocardial infarction.
BACKGROUND
Studies have postulated that cyclooxygenase-2 (COX-2) selective inhibitors affect cardiovascular risk through various mechanisms. Some of these mechanisms could increase risk (for example, inhibition of prostacyclin production), and some could decrease risk (for example, inhibition of inflammation).


OBJECTIVE
To determine the effect of COX-2 inhibitors on risk for nonfatal myocardial infarction (MI).


METHODS
Case-control study.


METHODS
36 hospitals in a 5-county area.


METHODS
1718 case-patients with a first, nonfatal MI admitted to these hospitals and 6800 controls randomly selected from the same counties.


METHODS
Self-reported medication use assessed through telephone interviews.


RESULTS
The adjusted odds ratio for MI among celecoxib users, relative to persons who did not use nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs), was 0.43 (95% CI, 0.23 to 0.79) compared with 1.16 (CI, 0.70 to 1.93) among rofecoxib users. The use of rofecoxib was associated with a statistically significant higher odds of MI compared with the use of celecoxib (adjusted odds ratio for rofecoxib vs. celecoxib, 2.72 [CI, 1.24 to 5.95]; P = 0.01). Nonselective NSAIDs were associated with a reduced odds of nonfatal MI relative to nonusers. Comparisons of COX-2 inhibitors with nonselective NSAIDs were the following: rofecoxib versus naproxen (odds ratio, 3.39 [CI, 1.37 to 8.40]) and celecoxib versus ibuprofen or diclofenac (odds ratio, 0.77 [CI, 0.40 to 1.48]).


CONCLUSIONS
The possibility of recall bias and uncontrolled confounding in this observational study limit the ability to make definitive conclusions. The association of celecoxib with a lower odds of MI could have occurred by chance. Only about 50% of eligible participants completed telephone interviews.


CONCLUSIONS
Celecoxib and rofecoxib were associated with different odds of MI. Cardiovascular effects among the COX-2 inhibitors seem different, but further studies, preferably randomized trials, are needed to fully understand the spectrum of effects of COX-2 inhibitors and potential differences among them.
Kimmel
Stephen E
SE
University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA.
Berlin
Jesse A
JA
Reilly
Muredach
M
Jaskowiak
Jane
J
Kishel
Lori
L
Chittams
Jesse
J
Strom
Brian L
BL
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000627:therapeutic use; D015982:Bias; D016022:Case-Control Studies; D000068579:Celecoxib; D015986:Confounding Factors, Epidemiologic; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004008:Diclofenac / Q000009:adverse effects; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000009:adverse effects; D007783:Lactones / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced*; D009288:Naproxen / Q000009:adverse effects; D016017:Odds Ratio; D011720:Pyrazoles / Q000009:adverse effects*; D012307:Risk Factors; D013449:Sulfonamides / Q000009:adverse effects*; D013450:Sulfones / Q000009:adverse effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007783:Lactones; D011720:Pyrazoles; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; D004008:Diclofenac; D009288:Naproxen; D000068579:Celecoxib; D001241:Aspirin; D007052:Ibuprofen