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Association of proton pump inhibitor use on cardiovascular outcomes with clopidogrel and ticagrelor: insights from the platelet inhibition and patient outcomes trial.
- Source :
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Circulation [Circulation] 2012 Feb 28; Vol. 125 (8), pp. 978-86. Date of Electronic Publication: 2012 Jan 18. - Publication Year :
- 2012
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Abstract
- Background: The clinical significance of the interaction between clopidogrel and proton pump inhibitors (PPIs) remains unclear.<br />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).<br />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.<br />Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
- Subjects :
- Adenosine adverse effects
Adenosine blood
Adenosine therapeutic use
Aged
Clopidogrel
Double-Blind Method
Female
Humans
Male
Middle Aged
Myocardial Infarction blood
Myocardial Infarction chemically induced
Platelet Aggregation Inhibitors adverse effects
Platelet Aggregation Inhibitors blood
Proton Pump Inhibitors adverse effects
Proton Pump Inhibitors blood
Stroke blood
Stroke chemically induced
Ticagrelor
Ticlopidine adverse effects
Ticlopidine blood
Ticlopidine therapeutic use
Treatment Outcome
Adenosine analogs & derivatives
Myocardial Infarction epidemiology
Platelet Aggregation Inhibitors therapeutic use
Proton Pump Inhibitors therapeutic use
Stroke epidemiology
Ticlopidine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 125
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 22261200
- Full Text :
- https://doi.org/10.1161/CIRCULATIONAHA.111.032912