title: Risk of new acute myocardial infarction hospitalization associated with use of oral and parenteral non-steroidal anti-inflammation drugs (NSAIDs): a case-crossover study of Taiwan's National Health Insurance claims database and review of current evidence.
abstract: BACKGROUND
  Previous studies have documented the increased cardiovascular risk associated with the use of some nonsteroidal anti-inflammatory drugs (NSAIDs). Despite this, many old NSAIDs are still prescribed worldwide. Most of the studies to date have been focused on specific oral drugs or limited by the number of cases examined. We studied the risk of new acute myocardial infarction (AMI) hospitalization with current use of a variety of oral and parenteral NSAIDs in a nationwide population, and compared our results with existing evidence.
  
  
  METHODS
  We conducted a case-crossover study using the Taiwan's National Health Insurance claim database, identifying patients with new AMI hospitalized in 2006. The 1-30 days and 91-120 days prior to the admission were defined as case and matched control period for each patient, respectively. Uses of NSAIDs during the respective periods were compared using conditional logistic regression and adjusted for use of co-medications.
  
  
  RESULTS
  8354 new AMI hospitalization patients fulfilled the study criteria. 14 oral and 3 parenteral NSAIDs were selected based on drug utilization profile among 13.7 million NSAID users. The adjusted odds ratio, aOR (95% confidence interval), for risk of AMI and use of oral and parenteral non-selective NSAIDs were 1.42 (1.29, 1.56) and 3.35 (2.50, 4.47), respectively, and significantly greater for parenteral than oral drugs (p for interaction<0.01). Ketorolac was associated with the highest AMI risk among both of oral and parenteral NSAIDs studied, the aORs were 2.02 (1.00, 4.09) and 4.27 (2.90, 6.29) respectively. Use of oral flurbiprofen, ibuprofen, sulindac, diclofenac, and parenteral ketoprofen were also significantly associated with increased AMI risk. The results of the present study were consistent with the majority of evidence from previous studies.
  
  
  CONCLUSIONS
  The collective evidence revealed the tendency of increased AMI risk with current use of some NSAIDs. A higher AMI risk associated with use of parenteral NSAIDs was observed in the present study. Ketorolac had the highest associated risk in both oral and parenteral NSAIDs studied. Though further investigation to confirm the association is warranted, prescribing physicians and the general public should be cautious about the potential risk of AMI when using NSAIDs.
authors.affiliation: Center for Drug Evaluation, Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, and Department of Internal Medicine, National Taiwan University Hospital, 5F18, No, 17, Hsuchow Road, Taipei 100, Taipei, Taiwan.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Shau
authors.forename: Hsi-Chieh
authors.initials: HC
authors.lastname: Chen
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Chen
authors.forename: Hsu-Wen
authors.initials: HW
authors.lastname: Chou
authors.forename: Chia-Hsuin
authors.initials: CH
authors.lastname: Chang
authors.forename: Chuei-Wen
authors.initials: CW
authors.lastname: Kuo
authors.forename: Mei-Shu
authors.initials: MS
authors.lastname: Lai
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D016208:Databases, Factual; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology; D016017:Odds Ratio; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors