title: Individual Proton Pump Inhibitors and Outcomes in Patients With Coronary Artery Disease on Dual Antiplatelet Therapy: A Systematic Review.
abstract: BACKGROUND
  Observational studies evaluating the possible interaction between proton pump inhibitors (PPIs) and clopidogrel have shown mixed results. We conducted a systematic review comparing the safety of individual PPIs in patients with coronary artery disease taking clopidogrel.
  
  
  RESULTS
  Studies performed from January 1995 to December 2013 were screened for inclusion. Data were extracted, and study quality was graded for 34 potential studies. For those studies in which follow-up period, outcomes, and multivariable adjustment were comparable, meta-analysis was performed.The adjusted odds or hazard ratios for the composite of cardiovascular or all-cause death, myocardial infarction, and stroke at 1 year were reported in 6 observational studies with data on individual PPIs. Random-effects meta-analyses of the 6 studies revealed an increased risk for adverse cardiovascular events for those taking pantoprazole (hazard ratio 1.38; 95% CI 1.12-1.70), lansoprazole (hazard ratio 1.29; 95% CI 1.09-1.52), or esomeprazole (hazard ratio 1.27; 95% CI 1.02-1.58) compared with patients on no PPI. This association was not significant for omeprazole (hazard ratio 1.16; 95% CI 0.93-1.44). Sensitivity analyses for the coronary artery disease population (acute coronary syndrome versus mixed) and exclusion of a single study due to heterogeneity of reported results did not have significant influence on the effect estimates for any PPIs.
  
  
  CONCLUSIONS
  Several frequently used PPIs previously thought to be safe for concomitant use with clopidogrel were associated with greater risk of adverse cardiovascular events. Although the data are observational, they highlight the need for randomized controlled trials to evaluate the safety of concomitant PPI and clopidogrel use in patients with coronary artery disease.
authors.affiliation: Division of Cardiovascular Medicine, Duke University Medical Center, Durham, NC (M.W.S., C.M., S.J.).
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Sherwood
authors.affiliation: Division of Cardiovascular Medicine, Duke University Medical Center, Durham, NC (M.W.S., C.M., S.J.).
authors.forename: Chiara
authors.initials: C
authors.lastname: Melloni
authors.affiliation: Division of Cardiovascular Medicine, Duke University Medical Center, Durham, NC (M.W.S., C.M., S.J.).
authors.forename: W Schuyler
authors.initials: WS
authors.lastname: Jones
authors.affiliation: Duke Heart Center, Duke University Medical Center, Durham, NC (J.B.W.).
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Washam
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC (V.H.).
authors.forename: Vic
authors.initials: V
authors.lastname: Hasselblad
authors.affiliation: Division of General Internal Medicine, Duke University Medical Center, Durham, NC (R.J.D.).
authors.forename: Rowena J
authors.initials: RJ
authors.lastname: Dolor
mesh_terms: D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D006801:Humans; D064887:Observational Studies as Topic; D016017:Odds Ratio; D061214:Patient Safety; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012307:Risk Factors; 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; D013988:Ticlopidine
keywords: adverse cardiovascular outcomes; clopidogrel; coronary artery disease; medication interaction; proton pump inhibitor