title: Relationship between cardiovascular outcomes and proton pump inhibitor use in patients receiving dual antiplatelet therapy after acute coronary syndrome.
abstract: BACKGROUND
  There is conflicting evidence regarding the potential interaction between clopidogrel and proton pump inhibitors (PPIs), with observational studies suggesting an increased risk of adverse cardiovascular (CV) outcomes and clinical trials suggesting there is no such risk.
  
  
  METHODS
  We conducted a retrospective cohort study to assess CV outcomes of 9753 patients taking dual antiplatelet therapy of aspirin plus clopidogrel with or without a PPI after hospitalization for acute coronary syndrome (ACS). Cox proportional hazards models were used to assess our primary endpoint of re-hospitalization for ACS in overall sample and a propensity score matching subsample.
  
  
  RESULTS
  Among patients taking clopidogrel plus aspirin, concomitant use of PPI was not associated with the risk of re-hospitalization for ACS (adjusted hazard ratio [HR] 1.12 [95%CI 0.72-1.73]). The findings were consistent in the propensity score matching cohort (adjusted HR 0.82 [95%CI 0.43-1.54]). Compared with PPI nonusers, there is no significant association between each specific PPI users and the risk of re-hospitalization for ACS (adjusted HR; omeprazole 0.96 [95%CI 0.35-2.66], pantoprazole 1.05 [95%CI 0.38-2.92], rabeprazole 0.60 [95%CI 0.17-2.17], esomeprazole 0.31 [95%CI 0.10-0.99], and lansoprazole 0.82 [95%CI 0.32-2.07]).
  
  
  CONCLUSIONS
  In conclusion, this population-based cohort study found that concomitant use of clopidogrel and PPI in patients who received dual antiplatelet therapy after ACS was not associated with risk of ACS re-hospitalization. Together, our study and findings of recently published clinical trials suggest that there was no apparent CV interaction between clopidogrel and PPI in patients who received dual antiplatelet therapy.
authors.affiliation: Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. fyshsiao@ntu.edu.tw
authors.forename: Fei-Yuan
authors.initials: FY
authors.lastname: Hsiao
authors.forename: C Daniel
authors.initials: CD
authors.lastname: Mullins
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Wen
authors.forename: Weng-Foung
authors.initials: WF
authors.lastname: Huang
authors.forename: Pei-Fen
authors.initials: PF
authors.lastname: Chen
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Tsai
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology*; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors; D001241:Aspirin / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D000077144:Clopidogrel; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D016208:Databases, Factual; D004347:Drug Interactions; D064098:Esomeprazole; D005260:Female; D041743:Herb-Drug Interactions; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000009:adverse effects / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole; D064098:Esomeprazole; D013988:Ticlopidine; D001241:Aspirin