Open AccessImpact of Proton Pump Inhibitor Therapy on the Efficacy of Clopidogrel in the CAPRIE and CREDO Trials
Author(s) -
Dunn Steven P.,
Steinhubl Steven R.,
Bauer Deborah,
Charnigo Richard J.,
Berger Peter B.,
Topol Eric J.
Publication year - 2013
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.112.004564
Subject(s) - medicine , clopidogrel , proton pump inhibitor , clinical trial , intensive care medicine , aspirin
Background Proton pump inhibitors ( PPI s) may interfere with the metabolic activation of clopidogrel via inhibition of cytochrome P450 2C19, but the clinical implications remain unclear. Methods and Results The impact of PPI use on the 1‐year primary end point (ischemic stroke, myocardial infarction [ MI ], or vascular death) in the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial and the 28‐day (all‐cause death, MI , or urgent target vessel revascularization) and 1‐year (all‐cause death, MI , or stroke) primary end points in the Clopidogrel for Reduction of Events During Observation (CREDO) trial were examined. Clopidogrel appeared to elevate risk for the primary end point in CAPRIE among PPI users (estimated hazard ratio [ EHR ] 2.66, 95% CI 0.94 to 7.50) while lowering it for non‐ PPI users ( EHR 0.90, 95% CI 0.83 to 0.99, interaction P =0.047). Moreover, PPI use was associated with worse outcomes in patients receiving clopidogrel ( EHR 2.39, 95% CI 1.74 to 3.28) but not aspirin ( EHR 1.04, 95% CI 0.70 to 1.57, interaction P =0.001). Clopidogrel did not significantly alter risk for the 1‐year primary end point in CREDO among PPI users ( EHR 0.82, 95% CI 0.48 to 1.40) while lowering it for non‐ PPI users ( EHR 0.71, 95% CI 0.52 to 0.98, interaction P =0.682). Also, PPI use was associated with worse outcomes in both patients receiving clopidogrel ( EHR 1.67, 95% CI 1.06 to 2.64) and those receiving placebo ( EHR 1.56, 95% CI 1.06 to 2.30, interaction P =0.811). Conclusions In CREDO , the efficacy of clopidogrel was not significantly affected by PPI use. However, in CAPRIE , clopidogrel was beneficial to non‐ PPI users while apparently harmful to PPI users. Whether this negative interaction is clinically important for patients receiving clopidogrel without aspirin needs further study.