title: Randomized double-blind placebo-controlled crossover study to determine the effects of esomeprazole on inhibition of platelet function by clopidogrel.
abstract: BACKGROUND
  Pharmacokinetic studies suggest that clopidogrel and esomeprazole are metabolized by similar hepatic enzymes; however, previous studies have not identified a biochemical interaction.
  
  
  OBJECTIVE
  To determine whether addition of esomeprazole to patients receiving aspirin and clopidogrel reduces the antiplatelet effects of clopidogrel.
  
  
  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 the first treatment period, after washout and following the second treatment period.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Esomeprazole when co-administered with aspirin and clopidogrel results in a significant attenuation of clopidogrel's antiplatelet effects.
authors.affiliation: Department of Cardiovascular Medicine, Alfred Hospital, Melbourne, Victoria, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Fernando
authors.forename: N
authors.initials: N
authors.lastname: Bassler
authors.forename: J
authors.initials: J
authors.lastname: Habersberger
authors.forename: L J
authors.initials: LJ
authors.lastname: Sheffield
authors.forename: R
authors.initials: R
authors.lastname: Sharma
authors.forename: A M
authors.initials: AM
authors.lastname: Dart
authors.forename: K H
authors.initials: KH
authors.lastname: Peter
authors.forename: J A
authors.initials: JA
authors.lastname: Shaw
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D001241:Aspirin / Q000008:administration & dosage; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000097:blood; D000077144:Clopidogrel; D018592:Cross-Over Studies; D065731:Cytochrome P-450 CYP2C19; D004311:Double-Blind Method; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D064098:Esomeprazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood; D008875:Middle Aged; D010641:Phenotype; D010750:Phosphoproteins / Q000097:blood; D015990:Placebo Effect; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010979:Platelet Function Tests; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018570:Risk Assessment; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013997:Time Factors; D014739:Victoria; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D064098:Esomeprazole; D013988:Ticlopidine; D001241:Aspirin