title: Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study.
abstract: BACKGROUND
  Controversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel.
  
  
  OBJECTIVE
  To examine the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction.
  
  
  METHODS
  A nationwide cohort study based on linked administrative registry data.
  
  
  METHODS
  All hospitals in Denmark.
  
  
  METHODS
  All patients discharged after first-time myocardial infarction from 2000 to 2006.
  
  
  METHODS
  The primary outcome was a composite of rehospitalization for myocardial infarction or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after myocardial infarction. Follow-up was 1 year.
  
  
  RESULTS
  Of 56 406 included patients, 9137 (16.2%) were re-hospitalized for myocardial infarction or stroke or experienced cardiovascular death. Of the 24 702 patients (43.8%) who received clopidogrel, 6753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for myocardial infarction or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% CI, 1.17 to 1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21 to 1.37). No statistically significant interaction occurred between a PPI and clopidogrel (P = 0.72).
  
  
  CONCLUSIONS
  Unmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible.
  
  
  CONCLUSIONS
  Proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone.
authors.affiliation: Copenhagen University Hospital Gentofte, Hellerup, Denmark. mc@heart.dk
authors.forename: Mette
authors.initials: M
authors.lastname: Charlot
authors.forename: Ole
authors.initials: O
authors.lastname: Ahlehoff
authors.forename: Mette Lykke
authors.initials: ML
authors.lastname: Norgaard
authors.forename: Casper H
authors.initials: CH
authors.lastname: Jørgensen
authors.forename: Rikke
authors.initials: R
authors.lastname: Sørensen
authors.forename: Steen Z
authors.initials: SZ
authors.lastname: Abildstrøm
authors.forename: Peter Riis
authors.initials: PR
authors.lastname: Hansen
authors.forename: Jan Kyst
authors.initials: JK
authors.lastname: Madsen
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.forename: Gunnar
authors.initials: G
authors.lastname: Gislason
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000401:mortality; D000077144:Clopidogrel; D015331:Cohort Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D016016:Proportional Hazards Models; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D012008:Recurrence; D012044:Regression Analysis; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine