Document Detail

COX-2 selective nonsteroidal anti-inflammatory drugs and risk of gastrointestinal tract complications and myocardial infarction: an instrumental variable analysis.
MedLine Citation:
PMID:  23532054     Owner:  NLM     Status:  MEDLINE    
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.
Neil M Davies; George Davey Smith; Frank Windmeijer; Richard M Martin
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  Epidemiology (Cambridge, Mass.)     Volume:  24     ISSN:  1531-5487     ISO Abbreviation:  Epidemiology     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-03     Completed Date:  2013-09-30     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  9009644     Medline TA:  Epidemiology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  352-62     Citation Subset:  IM    
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MeSH Terms
Aged, 80 and over
Anti-Inflammatory Agents, Non-Steroidal / adverse effects
Confounding Factors (Epidemiology)
Cyclooxygenase 2 Inhibitors / adverse effects*
Data Interpretation, Statistical
Databases, Factual
Follow-Up Studies
Gastrointestinal Diseases / chemically induced*
Least-Squares Analysis
Middle Aged
Models, Statistical
Multivariate Analysis
Myocardial Infarction / chemically induced*
Prospective Studies
Regression Analysis
Grant Support
G0600705//Medical Research Council
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Cyclooxygenase 2 Inhibitors
Comment In:
Epidemiology. 2013 May;24(3):370-4   [PMID:  23549180 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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