title: Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from the platelet inhibition and patient outcomes trial.
abstract: BACKGROUND
  The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear.
  
  
  RESULTS
  We examined the relationship between PPI use and 1-year cardiovascular events (cardiovascular death, myocardial infarction, or stroke) in patients with acute coronary syndrome randomized to clopidogrel or ticagrelor in a prespecified, nonrandomized subgroup analysis of the Platelet Inhibition and Patient Outcomes (PLATO) trial. The primary end point rates were higher for individuals on a PPI (n=6539) compared with those not on a PPI (n=12 060) at randomization in both the clopidogrel (13.0% versus 10.9%; adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.04-1.38) and ticagrelor (11.0% versus 9.2%; HR, 1.24; 95% CI, 1.07-1.45) groups. Patients on non-PPI gastrointestinal drugs had similar primary end point rates compared with those on a PPI (PPI versus non-PPI gastrointestinal treatment: clopidogrel, HR, 0.98; 95% CI, 0.79-1.23; ticagrelor, HR, 0.89; 95% CI, 0.73-1.10). In contrast, patients on no gastric therapy had a significantly lower primary end point rate (PPI versus no gastrointestinal treatment: clopidogrel, HR, 1.29; 95% CI, 1.12-1.49; ticagrelor, HR, 1.30; 95% CI, 1.14-1.49).
  
  
  CONCLUSIONS
  The use of a PPI was independently associated with a higher rate of cardiovascular events in patients with acute coronary syndrome receiving clopidogrel. However, a similar association was observed between cardiovascular events and PPI use during ticagrelor treatment and with other non-PPI gastrointestinal treatment. Therefore, in the PLATO trial, the association between PPI use and adverse events may be due to confounding, with PPI use more of a marker for, than a cause of, higher rates of cardiovascular events.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
authors.affiliation: MSc, Division of Cardiology, St. Michael's Hospital, 30 Bond St, Room 6-034, Queen, Toronto, Ontario, Canada M5B 1W8. goodmans@chrc.net
authors.forename: Shaun G
authors.initials: SG
authors.lastname: Goodman
authors.forename: Robert
authors.initials: R
authors.lastname: Clare
authors.forename: Karen S
authors.initials: KS
authors.lastname: Pieper
authors.forename: José C
authors.initials: JC
authors.lastname: Nicolau
authors.forename: Robert F
authors.initials: RF
authors.lastname: Storey
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Cantor
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Mahaffey
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Steen
authors.initials: S
authors.lastname: Husted
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Cannon
authors.forename: Stefan K
authors.initials: SK
authors.lastname: James
authors.forename: Jan
authors.initials: J
authors.lastname: Kilhamn
authors.forename: P Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrington
authors.forename: Lars
authors.initials: L
authors.lastname: Wallentin
mesh_terms: D000241:Adenosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D000368:Aged; D000077144:Clopidogrel; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology*; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D020521:Stroke / Q000097:blood / Q000139:chemically induced / Q000453:epidemiology*; D000077486:Ticagrelor; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine