title: Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial.
abstract: BACKGROUND
  Proton pump inhibitors (PPIs) are frequently prescribed in combination with clopidogrel, but conflicting data exist as to whether PPIs diminish the efficacy of clopidogrel. We assessed the association between PPI use and clinical outcomes for patients treated with percutaneous coronary intervention (PCI) and dual-antiplatelet therapy (DAPT) with clopidogrel plus aspirin.
  
  
  RESULTS
  In the PRODIGY trial, 1,970 patients were randomized to 6- or 24-month DAPT at 30 days from index procedure. Among them, 738 patients (37.5%) received PPI (mainly lansoprazole; 90.1%) at the time of randomization. Proton pump inhibitor users were older, were most likely to be woman, had a lower creatinine clearance, presented more frequently with acute coronary syndrome, and had a higher CRUSADE bleeding score. After adjustment, the primary efficacy end point (composite of all-cause death, myocardial infarction, and cerebrovascular accident) was similar between no PPI and PPI users (9.2% vs 11.5%, adjusted hazard ratio [HR] 1.051, 95% CI 0.788-1.400, P = .736). Bleeding rates did not differ between the 2 groups (Bleeding Academic Research Consortium type 2, 3, or 5: adjusted HR 0.996, 95% CI 0.672-1.474, P = .980). Net clinical adverse events were also similar in no PPI and PPI patients (12.9% vs 14.9%, adjusted HR 0.99, 95% CI 0.772-1.268, P = .93). Results remained consistent at sensitivity analysis when focusing on the 548 patients who remained on PPI for the whole study duration.
  
  
  CONCLUSIONS
  The current findings suggest that the concomitant use of PPIs, when clinically indicated, in patients receiving clopidogrel is not associated with adverse clinical outcome.
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern, Switzerland; Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gargiulo
authors.affiliation: Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Clinical and Experimental Medicine, Policlinico "G. Martino," University of Messina, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Costa
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern, Switzerland.
authors.forename: Sara
authors.initials: S
authors.lastname: Ariotti
authors.affiliation: Cardiovascular Institute, Azienda Ospedaliero-Universitaria Sant'Anna, Ferrara, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Biscaglia
authors.affiliation: Cardiovascular Institute, Azienda Ospedaliero-Universitaria Sant'Anna, Ferrara, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Campo
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.affiliation: Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Leonardi
authors.affiliation: Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Hasselt, Belgium.
authors.forename: Pascal
authors.initials: P
authors.lastname: Vranckx
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Windecker
authors.affiliation: Department of Cardiology, Bern University Hospital, Bern, Switzerland; Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands. Electronic address: marco.valgimigli@insel.ch.
authors.forename: Marco
authors.initials: M
authors.lastname: Valgimigli
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage; D000077144:Clopidogrel; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology* / Q000601:surgery; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006083:Graft Occlusion, Vascular / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D006801:Humans; D006965:Hyperplasia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000601:surgery*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D015607:Stents / Q000009:adverse effects*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D013997:Time Factors; D016896:Treatment Outcome; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin