The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults

Ann Intern Med. 2005 Apr 5;142(7):481-9. doi: 10.7326/0003-4819-142-7-200504050-00113.


Background: Cyclooxygenase-2 (COX-2) selective inhibitors have been marketed since 1999 as safer alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs). Debate about their cardiac safety has culminated in the recent withdrawal of rofecoxib. Additional studies are needed to better understand this risk and to determine whether this safety concern represents a class effect.

Objective: To assess the influence of various NSAIDs on the risk for a first myocardial infarction (MI).

Design: Population-based, retrospective cohort study analyzed using a time-matched, nested case-control approach.

Setting: Quebec, Canada.

Participants: 113,927 elderly persons without previous MI and newly treated with an NSAID between 1 January 1999 and 30 June 2002.

Measurements: NSAID exposure and occurrence of MI assessed by using Quebec's administrative health databases.

Results: Compared with no use of NSAIDs in the year preceding the event, current use of rofecoxib was associated with an increased risk for an acute MI (rate ratio [RR], 1.24 [95% CI, 1.05 to 1.46]) that was more pronounced at higher doses (RR, 1.73 [CI, 1.09 to 2.76]). The concomitant use of aspirin appears to decrease the risk associated with low-dose rofecoxib (RR, 1.00 [CI, 0.77 to 1.28]) but not with high-dose rofecoxib (RR, 2.36 [CI, 1.27 to 4.39]). No increased risks were observed with celecoxib (RR, 0.99 [CI, 0.85 to 1.16]) or the other NSAIDs.

Limitations: The study could not completely account for all potential confounders, including over-the-counter use of aspirin and ibuprofen.

Conclusions: These results provide evidence of an increased risk for acute MI in current users of rofecoxib among elderly persons with no history of MI. This risk appears greater at higher doses. Aspirin use mitigates the risk associated with low-dose but not high-dose rofecoxib. There was no evidence of an increased risk with the other NSAIDs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Aspirin / therapeutic use
  • Case-Control Studies
  • Cohort Studies
  • Confounding Factors, Epidemiologic
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / administration & dosage
  • Cyclooxygenase Inhibitors / adverse effects*
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Membrane Proteins
  • Myocardial Infarction / chemically induced*
  • Prostaglandin-Endoperoxide Synthases / administration & dosage
  • Prostaglandin-Endoperoxide Synthases / adverse effects*
  • Retrospective Studies
  • Risk Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin