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Association of Proton Pump Inhibitor Use on Cardiovascular Outcomes With Clopidogrel and Ticagrelor: Outcomes With Clopidogrel and Ticagrelor
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2012 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 8, 978-986 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2012. Vol. 125, no 8, 978-986 p.
Keyword [en]
acute coronary syndrome, clopidogrel, mortality, myocardial infarction, ticagrelor
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-172047DOI: 10.1161/CIRCULATIONAHA.111.032912ISI: 000300951700013OAI: oai:DiVA.org:uu-172047DiVA: diva2:513367
Available from: 2012-04-02 Created: 2012-04-01 Last updated: 2013-01-09Bibliographically approved

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James, Stefan KWallentin, Lars
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