title: COX-2 selective nonsteroidal anti-inflammatory drugs and risk of gastrointestinal tract complications and myocardial infarction: an instrumental variable analysis.
abstract: OBJECTIVE
  Instrumental variable analysis can estimate treatment effects in the presence of residual or unmeasured confounding. We compared ordinary least squares regression versus instrumental variable estimates of the effects of selective cyclooxygenase-2 inhibitors (COX-2s) relative to nonselective nonsteroidal anti-inflammatory drug (NSAID) prescriptions on incidence of upper gastrointestinal complications and myocardial infarction (MI).
  
  
  METHODS
  We sampled a cohort of 62,933 first-time users of COX-2s or nonselective NSAIDs older than 60 years in the Clinical Practice Research Datalink. The instruments were physicians' previous prescriptions of COX-2s or nonselective NSAIDs, which are surrogates for physician preferences. We estimated risk differences of incident upper gastrointestinal complications and MI within 180 days of first COX-2 versus nonselective NSAID prescription.
  
  
  RESULTS
  Using ordinary least squares regression, adjusted for baseline confounders, we observed little association of COX-2 prescriptions with incident upper gastrointestinal complications (risk difference = -0.08 [95% confidence interval = -0.20 to 0.04]) or MI (0.06 [-0.06 to 0.17]) per 100 patients treated. Our adjusted instrumental variable results suggested 0.46 per 100 (-0.15 to 1.07) fewer upper gastrointestinal complications and little difference in acute MIs (0.08 per 100 [-0.61 to 0.76]), within 180 days of being prescribed COX-2s. Estimates were more precise when we used 20 previous prescriptions; the instrumental variable analysis implied 0.74 (0.28 to 1.19) fewer MIs per 100 patients prescribed COX-2s.
  
  
  CONCLUSIONS
  Using instrumental variable analysis, we found some evidence that COX-2 prescriptions reduced the risk of upper gastrointestinal complications, consistent with randomized controlled trials. Our results using multiple instruments suggest that COX-2s may have heterogeneous within-class effects on MI.
authors.affiliation: Medical Research Council Centre for Causal Analyses and Translational Epidemiology, School of Social and Community Medicine, Faculty of Medicine and Dentistry, University of Bristol, Barley House, Oakfield Grove, Bristol, United Kingdom. neil.davies@bristol.ac.uk
authors.forename: Neil M
authors.initials: NM
authors.lastname: Davies
authors.forename: George Davey
authors.initials: GD
authors.lastname: Smith
authors.forename: Frank
authors.initials: F
authors.lastname: Windmeijer
authors.forename: Richard M
authors.initials: RM
authors.lastname: Martin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D015986:Confounding Factors, Epidemiologic; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000139:chemically induced*; D011446:Prospective Studies; D012044:Regression Analysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors