title: The risk for myocardial infarction with cyclooxygenase-2 inhibitors: a population study of elderly adults.
abstract: 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).
  
  
  METHODS
  Population-based, retrospective cohort study analyzed using a time-matched, nested case-control approach.
  
  
  METHODS
  Quebec, Canada.
  
  
  METHODS
  113,927 elderly persons without previous MI and newly treated with an NSAID between 1 January 1999 and 30 June 2002.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: McGill University Health Centre, McGill University, Montréal, Québec, Canada.
authors.forename: Linda E
authors.initials: LE
authors.lastname: Lévesque
authors.forename: James M
authors.initials: JM
authors.lastname: Brophy
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D016022:Case-Control Studies; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D009203:Myocardial Infarction / Q000139:chemically induced*; D011451:Prostaglandin-Endoperoxide Synthases / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin