Risk of myocardial infarction associated with selective COX-2 inhibitors: meta-analysis of randomised controlled trials.
OBJECTIVE
To evaluate the risk of myocardial infarction (MI) associated with the use of selective cyclooxygenase-2 (COX-2) inhibitors (coxibs).


METHODS
Systematic review and meta-analysis of randomised controlled trials (RCTs) using a fixed-effect model to estimate the odds ratios (ORs) for risk of MI associated with coxibs compared against placebo, non-steroidal anti-inflammatory drugs (NSAIDs) and other coxibs.


RESULTS
Fifty-five trials (99 087 patients) were included in the meta-analysis. The overall pooled OR for MI risk for any coxib compared against placebo was 1.46 (95%CI: 1.02, 2.09). We found celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib were associated with higher MI risks compared against placebo. The pooled OR for any coxib compared against other NSAIDs was 1.45 (95%CI: 1.09, 1.93). Rofecoxib had a significantly higher risk of MI than naproxen (OR: 5.39; 95%: 2.08, 14.02) and valdecoxib had lower MI risk than diclofenac (OR: 0.14, 95%CI: 0.03, 0.73). There were no significant differences identified in the risk of MI from the available head-to-head comparisons of coxibs.


CONCLUSIONS
Coxibs were associated with increased risks of MI when compared against placebo or non-selective NSAIDs. Differences in MI risk were also apparent between comparisons of individual NSAIDs. Future work should consider using individual patient data (IPD) meta-analysis to explore differences in MI risk between different subgroups of patients.
Chen
Li-Chia
LC
School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Oxford Road, Manchester, UK.
Ashcroft
Darren M
DM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D000077613:Etoricoxib; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects; D015233:Models, Statistical; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D009288:Naproxen / Q000009:adverse effects; D016017:Odds Ratio; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D012307:Risk Factors; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects; D000096926:Benzenesulfonamides
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors; D004008:Diclofenac; D000077613:Etoricoxib; D007555:Isoxazoles; D007783:Lactones; D009288:Naproxen; D011720:Pyrazoles; D011725:Pyridines; D013449:Sulfonamides; D013450:Sulfones; C116926:rofecoxib; C406224:valdecoxib; D000096926:Benzenesulfonamides; C473384:lumiracoxib