Randomized double-blind placebo-controlled crossover study to determine the effects of esomeprazole on inhibition of platelet function by clopidogrel JOURNAL OF THROMBOSIS AND HAEMOSTASIS Fernando, H., Bassler, N., Habersberger, J., Sheffield, L. J., Sharma, R., Dart, A. M., Peter, K. H., Shaw, J. A. 2011; 9 (8): 1582–89


Pharmacokinetic studies suggest that clopidogrel and esomeprazole are metabolized by similar hepatic enzymes; however, previous studies have not identified a biochemical interaction.To determine whether addition of esomeprazole to patients receiving aspirin and clopidogrel reduces the antiplatelet effects of clopidogrel.Patients with a history of an acute coronary syndrome who had previously received clopidogrel were recruited. Subjects were commenced on clopidogrel and randomized to one of two treatment arms (esomeprazole or placebo) for 6 weeks. Following a 2-week washout period for study medications, patients were crossed over onto the alternative treatment arm for a further 6 weeks. Platelet function tests were undertaken at baseline, following the first treatment period, after washout and following the second treatment period.Thirty-one patients were enrolled. Significant attenuation of clopidogrel's antiplatelet effects was seen with co-administration of esomeprazole compared with placebo. Vasodilator stimulated phosphoprotein (VASP), platelet aggregometry (area under the curve (AUC)) and VerifyNow results were 54.7% ± 2.8 platelet reactivity index (PRI), 66.3 ± 2.6 AUC units and 213.1 ± 14.1 platelet reactivity units (PRU) with esomeprazole vs. 47% ± 2.7 PRI, 59.7 ± 3.7 AUC units and 181.4 ± 14.6 PRU with placebo (P < 0.01 esomeprazole vs. placebo for all measures). There was no significant difference in platelet aggregometry (maximal aggregation) between the esomeprazole group (68.9% ± 2.7 units) and placebo-treated group (64.5% ± 4.1 units; P > 0.05).Esomeprazole when co-administered with aspirin and clopidogrel results in a significant attenuation of clopidogrel's antiplatelet effects.

View details for DOI 10.1111/j.1538-7836.2011.04414.x

View details for Web of Science ID 000293791400019

View details for PubMedID 21696537