Platelet Activity Associated with Concomitant Use of Clopidogrel and Proton Pump Inhibitors in Children with Cardiovascular Disease

Context. In adults with acute coronary syndrome, decreased platelet inhibition associated with concomitant use of clopidogrel and proton pump inhibitors (PPI) has been reported. Objective. To evaluate platelet activity associated with PPI + clopidogrel vs. clopidogrel alone in children enrolled in the Platelet Inhibition in Children On cLOpidogrel (PICOLO) trial of clopidogrel in children with a cardiac condition at risk for arterial thrombosis. Design. Patients 0-24 m randomized to active therapy in the PICOLO trial were included in the present analysis. Platelet aggregation inhibition at baseline and steady state were evaluated in patients taking clopidogrel + PPI vs. clopidogrel only in the overall cohort and sub-group of clopidogrel responders. Results. A total of 49 patients were included (44 clopidogrel only, five clopidogrel + PPI); median age 38 days (interquartile range [IQR] 17-157 days). The majority of patients in each group had undergone systemic-to-pulmonary artery shunt. Compared with the clopidogrel group, patients in the clopidogrel + PPI group had a trend toward lower percent inhibition of maximum extent of platelet aggregation overall (median 6%, IQR 0-44% vs. 49%, IQR 19-63%, P = 0.09), and a significant reduction in the clopidogrel responders sub-group (median 25%, IQR 3-45% vs. 53%, IQR 38-65%, P = 0.04). There was no difference in percent inhibition of rate of platelet aggregation. Conclusions. Concomitant use of PPI + clopidogrel may be associated with decreased platelet inhibition in children with cardiac disease. Further study in a larger population and assessment of associated clinical outcomes is warranted.