Randomised Double Blind Placebo Controlled Crossover Study to Determine the Effects of Esomeprazole on Inhibition of Platelet Function by Clopidogrel.
J Thromb Haemost. 2011 Jun 22;
Authors: Fernando H, Bassler N, Habersberger J, Sheffield LJ, Sharma R, Dart AM, Peter KH, Shaw JA
Background: Pharmacokinetic studies suggest clopidogrel and esomeprazole are metabolized by similar hepatic enzymes however previous studies have not identified a biochemical interaction. Objectives: To determine whether addition of esomeprazole to patients receiving aspirin and clopidogrel reduces the antiplatelet effects of clopidogrel. Patient/Methods: 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 first treatment period, after washout and following second treatment period. Results: 31 patients were enrolled. Significant attenuation of clopidogrel's antiplatelet effects was seen with co-administration of esomeprazole compared to 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 versus placebo for all measures). There was no significant difference in platelet aggregometry (maximal aggregation) between the esomeprazole (68.9%± 2.7 units) and placebo treated groups (64.5%± 4.1 units) (p>0.05). Conclusion: Esomeprazole when co-administered with aspirin and clopidogrel results in a significant attenuation of clopidogrel's antiplatelet effects.
PMID: 21696537 [PubMed - as supplied by publisher]