Document Detail

Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from the platelet inhibition and patient outcomes trial.
MedLine Citation:
PMID:  22261200     Owner:  NLM     Status:  MEDLINE    
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: Unique identifier: NCT00391872.
Shaun G Goodman; Robert Clare; Karen S Pieper; José C Nicolau; Robert F Storey; Warren J Cantor; Kenneth W Mahaffey; Dominick J Angiolillo; Steen Husted; Christopher P Cannon; Stefan K James; Jan Kilhamn; P Gabriel Steg; Robert A Harrington; Lars Wallentin;
Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-01-18
Journal Detail:
Title:  Circulation     Volume:  125     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-28     Completed Date:  2012-04-19     Revised Date:  2012-11-05    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  978-86     Citation Subset:  AIM; IM    
MSc, Division of Cardiology, St. Michael's Hospital, 30 Bond St, Room 6-034, Queen, Toronto, Ontario, Canada M5B 1W8.
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MeSH Terms
Adenosine / adverse effects,  analogs & derivatives*,  blood,  therapeutic use
Double-Blind Method
Middle Aged
Myocardial Infarction / blood,  chemically induced,  epidemiology*
Platelet Aggregation Inhibitors / adverse effects,  blood,  therapeutic use*
Proton Pump Inhibitors / adverse effects,  blood,  therapeutic use*
Stroke / blood,  chemically induced,  epidemiology*
Ticlopidine / adverse effects,  analogs & derivatives*,  blood,  therapeutic use
Treatment Outcome
Reg. No./Substance:
0/Platelet Aggregation Inhibitors; 0/Proton Pump Inhibitors; 0/Ticagrelor; 55142-85-3/Ticlopidine; 58-61-7/Adenosine; 90055-48-4/clopidogrel
Comment In:
Circulation. 2012 Sep 11;126(11):e170; author reply e171-2   [PMID:  22965784 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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