Risk of myocardial infarction associated with selective COX-2 inhibitors: meta-analysis of randomised controlled trials

Pharmacoepidemiol Drug Saf. 2007 Jul;16(7):762-72. doi: 10.1002/pds.1409.

Abstract

Purpose: 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.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Celecoxib
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / adverse effects*
  • Diclofenac / administration & dosage
  • Diclofenac / adverse effects
  • Diclofenac / analogs & derivatives
  • Dose-Response Relationship, Drug
  • Etoricoxib
  • Humans
  • Isoxazoles / administration & dosage
  • Isoxazoles / adverse effects
  • Lactones / administration & dosage
  • Lactones / adverse effects
  • Models, Statistical
  • Myocardial Infarction / chemically induced*
  • Myocardial Infarction / epidemiology
  • Naproxen / adverse effects
  • Odds Ratio
  • Pyrazoles / administration & dosage
  • Pyrazoles / adverse effects
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Randomized Controlled Trials as Topic
  • Risk
  • Risk Factors
  • Sulfonamides / administration & dosage
  • Sulfonamides / adverse effects
  • Sulfones / administration & dosage
  • Sulfones / adverse effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Isoxazoles
  • Lactones
  • Pyrazoles
  • Pyridines
  • Sulfonamides
  • Sulfones
  • rofecoxib
  • Diclofenac
  • valdecoxib
  • Naproxen
  • Celecoxib
  • lumiracoxib
  • Etoricoxib