title: Impact of proton pump inhibitors and dual antiplatelet therapy cessation on outcomes following percutaneous coronary intervention: Results From the PARIS Registry.
abstract: BACKGROUND
  Proton pump inhibitors (PPI) may decrease the availability of clopidogrel by competitive antagonism, leading to a potential increase in ischemic events.
  
  
  METHODS
  We evaluated patients from the all-comer PARIS registry treated with dual antiplatelet therapy (DAPT) with aspirin and clopidogrel following coronary stenting for outcomes stratified by PPI use. Two-year major adverse cardiovascular events (MACE), composite of cardiac death, myocardial infarction, definite or probable stent thrombosis or target lesion revascularization (TLR), and net adverse cardiac events (NACE), composite of MACE or Bleeding Academic Research consortium (BARC) type 3 or 5 bleeding were assessed. We also explored associations between PPI use and patterns of 2-year DAPT cessation.
  
  
  RESULTS
  The cohort comprised 4635 patients (23% PPI users) with mean age 64.4 ±11.4 years. Two year adjusted risk of MACE (HR: 1.27, 95% CI: 1.04-1.55), NACE (HR: 1.21, 95% CI: 1.01-1.44) and TLR (HR: 1.33, 95% CI: 1.04-1.71) were significantly higher in PPI users vs. non-users, without a difference in bleeding. Although the incidence of 2-year DAPT discontinuation and interruption was similar, DAPT disruption was significantly lower among PPI users vs. non-users (10.0% vs. 14.7%, P <0.0001). Compared to non-PPI users on continued DAPT, disruption was associated with higher MACE in both PPI users (HR: 2.34, 95% CI: 1.38-3.97) and non-users (HR: 1.41, 95% CI: 1.02-1.94) but greater BARC 3,5 bleeding only in non-PPI users (HR: 2.06, 95% CI: 1.21-3.51).
  
  
  CONCLUSIONS
  In clopidogrel treated PCI patients, the 2-year adjusted risk of MACE and NACE was significantly higher in PPI users driven by higher TLR compared to non-PPI users, without a difference in bleeding. PPI use was associated with lower incidence of DAPT disruption without an increase in disruption related bleeding compared to non-PPI users on DAPT. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
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authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Sameer
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authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Usman
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authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
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authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
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authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
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authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
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authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
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authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
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authors.affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Cono
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authors.affiliation: San Raffaele Hospital, Milan, Italy.
authors.forename: Antonio
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authors.lastname: Colombo
authors.affiliation: San Raffaele Hospital, Milan, Italy.
authors.forename: Alaide
authors.initials: A
authors.lastname: Chieffo
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Annapoorna
authors.initials: A
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authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
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authors.affiliation: Harvard Medical School, Cambridge, Massachusetts.
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authors.affiliation: Helios Amper-Klinikum, Dachau, Germany.
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authors.affiliation: St Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri.
authors.forename: David
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authors.lastname: Cohen
authors.affiliation: University of Kentucky, Lexington, Kentucky.
authors.forename: David
authors.initials: D
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authors.affiliation: Moses Cone Heart and Vascular Center, LeBauer Cardiovascular Research Foundation, Greensboro, North Carolina.
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authors.affiliation: Cedars-Sinai Medical Center, Los Angeles.
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authors.lastname: Henry
authors.affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Stuart
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authors.lastname: Pocock
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: George
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authors.affiliation: Hôpital Bichat-Claude Bernard, Paris, France.
authors.forename: P
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authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Roxana
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mesh_terms: D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D000077144:Clopidogrel; D003328:Coronary Thrombosis / Q000209:etiology; D004334:Drug Administration Schedule; D004336:Drug Antagonism; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology; D017202:Myocardial Ischemia / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation / Q000401:mortality; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D016016:Proportional Hazards Models; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D012042:Registries; D012307:Risk Factors; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: P2Y12 receptor inhibitor; dual antiplatelet therapy cessation; percutaneous coronary intervention; proton pump inhibitor; thienopyridine