title: Safety of clopidogrel and proton pump inhibitors in patients undergoing drug-eluting stent implantation.
abstract: OBJECTIVE
  A pharmacodynamic interaction between clopidogrel and proton pump inhibitors (PPIs) has been suggested, leading to reduced clopidogrel-induced platelet inhibitory effects. However, data from clinical studies are conflicting. The aim of this study was to evaluate the safety of long-term clopidogrel and PPI therapy.
  
  
  METHODS
  A total of 1328 consecutive patients (age 63±11 years; 81% male) undergoing drug-eluting stent implantation and 1-year follow-up were included. All patients were treated with a standard aspirin and clopidogrel treatment regimen for 12 months. The concomitant PPI therapy for the same duration was at the discretion of the clinical cardiologist. PPI therapy included lansoprazole (30 mg/day), pantoprazole (20 mg/day), or omeprazole (20 mg/day). At 1-year follow-up, major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), acute coronary syndrome leading to hospitalization and nonfatal stroke, were recorded. All cause death, any stent thrombosis (ST), and bleeding (Thrombolysis in MI major and minor) were also assessed.
  
  
  RESULTS
  Lansoprazole, pantoprazole, and omeprazole were administered to 855, 178, and 125 patients, whereas 170 were not prescribed any PPI therapy. Among patients treated with PPIs, those on pantoprazole had more often prior MI, multivessel coronary artery disease, and chronic kidney disease, whereas earlier peptic ulcer was more frequent among patients treated with omeprazole. The incidence of 1-year MACE was not statistically different between patients in the PPI and no-PPI groups (7.5 vs. 5.0%; P=0.26). Similarly, 1-year rates of all cause death, ST, and Thrombolysis in MI major and minor bleedings did not significantly differ. After statistical adjustment for potential confounders, the concomitant use of clopidogrel and PPIs was not associated with the risk of 1-year MACE [odds ratio (OR) 1.54, P=0.38], death (OR: 0.97, P=0.961), and ST (OR: 1.01, P=0.998). No differences across the three PPI types were found.
  
  
  CONCLUSIONS
  The association of clopidogrel and PPIs after drug-eluting stent implantation, prescribed on clinical judgement, seems safe.
authors.affiliation: Cardiovascular Department, Ospedali Riuniti di Bergamo, Bergamo, Italy. roberta_rossini@yahoo.it
authors.forename: Roberta
authors.initials: R
authors.lastname: Rossini
authors.forename: Davide
authors.initials: D
authors.lastname: Capodanno
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Musumeci
authors.forename: Corrado
authors.initials: C
authors.lastname: Lettieri
authors.forename: Nikoloz
authors.initials: N
authors.lastname: Lortkipanidze
authors.forename: Michele
authors.initials: M
authors.lastname: Romano
authors.forename: Tamar
authors.initials: T
authors.lastname: Nijaradze
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tarantini
authors.forename: Nicola
authors.initials: N
authors.lastname: Cicorella
authors.forename: Vasile
authors.initials: V
authors.lastname: Sirbu
authors.forename: Giulio
authors.initials: G
authors.lastname: Guagliumi
authors.forename: Renato
authors.initials: R
authors.lastname: Rosiello
authors.forename: Orazio
authors.initials: O
authors.lastname: Valsecchi
authors.forename: Antonello
authors.initials: A
authors.lastname: Gavazzi
mesh_terms: D054058:Acute Coronary Syndrome / Q000139:chemically induced; D000368:Aged; D019917:Blood Vessel Prosthesis Implantation; D000077144:Clopidogrel; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine