Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from the platelet inhibition and patient outcomes trial.

Published

Journal Article

BACKGROUND: The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear. METHODS AND 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. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.

Full Text

Cited Authors

  • Goodman, SG; Clare, R; Pieper, KS; Nicolau, JC; Storey, RF; Cantor, WJ; Mahaffey, KW; Angiolillo, DJ; Husted, S; Cannon, CP; James, SK; Kilhamn, J; Steg, PG; Harrington, RA; Wallentin, L; Platelet Inhibition and Patient Outcomes Trial Investigators,

Published Date

  • February 2012

Published In

Volume / Issue

  • 125 / 8

Start / End Page

  • 978 - 986

PubMed ID

  • 22261200

Pubmed Central ID

  • 22261200

Electronic International Standard Serial Number (EISSN)

  • 1524-4539

International Standard Serial Number (ISSN)

  • 0009-7322

Digital Object Identifier (DOI)

  • 10.1161/circulationaha.111.032912

Language

  • eng