title: Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population.
abstract: OBJECTIVE
  Proton pump inhibitors (PPIs) have been associated with adverse clinical outcomes amongst clopidogrel users after an acute coronary syndrome. Recent pre-clinical results suggest that this risk might extend to subjects without any prior history of cardiovascular disease. We explore this potential risk in the general population via data-mining approaches.
  
  
  METHODS
  Using a novel approach for mining clinical data for pharmacovigilance, we queried over 16 million clinical documents on 2.9 million individuals to examine whether PPI usage was associated with cardiovascular risk in the general population.
  
  
  RESULTS
  In multiple data sources, we found gastroesophageal reflux disease (GERD) patients exposed to PPIs to have a 1.16 fold increased association (95% CI 1.09-1.24) with myocardial infarction (MI). Survival analysis in a prospective cohort found a two-fold (HR = 2.00; 95% CI 1.07-3.78; P = 0.031) increase in association with cardiovascular mortality. We found that this association exists regardless of clopidogrel use. We also found that H2 blockers, an alternate treatment for GERD, were not associated with increased cardiovascular risk; had they been in place, such pharmacovigilance algorithms could have flagged this risk as early as the year 2000.
  
  
  CONCLUSIONS
  Consistent with our pre-clinical findings that PPIs may adversely impact vascular function, our data-mining study supports the association of PPI exposure with risk for MI in the general population. These data provide an example of how a combination of experimental studies and data-mining approaches can be applied to prioritize drug safety signals for further investigation.
authors.affiliation: Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, United States of America.
authors.forename: Nigam H
authors.initials: NH
authors.lastname: Shah
authors.affiliation: Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, United States of America.
authors.forename: Paea
authors.initials: P
authors.lastname: LePendu
authors.affiliation: Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Bauer-Mehren
authors.affiliation: Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, United States of America.
authors.forename: Yohannes T
authors.initials: YT
authors.lastname: Ghebremariam
authors.affiliation: Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, United States of America.
authors.forename: Srinivasan V
authors.initials: SV
authors.lastname: Iyer
authors.affiliation: Practice Fusion, Inc., San Francisco, CA, United States of America.
authors.forename: Jake
authors.initials: J
authors.lastname: Marcus
authors.affiliation: Divisions of Cardiovascular Medicine and Vascular Surgery, Stanford University, Stanford, CA, United States of America.
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Nead
authors.affiliation: Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, United States of America.
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.affiliation: Divisions of Cardiovascular Medicine and Vascular Surgery, Stanford University, Stanford, CA, United States of America.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Leeper
mesh_terms: D000328:Adult; D000077144:Clopidogrel; D006801:Humans; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced*; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D055815:Young Adult
chemical_list: D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine