title: Impact of Intravenous Lysine Acetylsalicylate Versus Oral Aspirin on Prasugrel-Inhibited Platelets: Results of a Prospective, Randomized, Crossover Study (the ECCLIPSE Trial).
abstract: BACKGROUND
  Prasugrel and ticagrelor, new P2Y12-adenosine diphosphate receptor antagonists, are associated with greater pharmacodynamic inhibition and reduction of cardiovascular events compared with clopidogrel in patients with an acute coronary syndrome. However, evidence is lacking about the effects of achieving faster and stronger cyclooxygenase inhibition with intravenous lysine acetylsalicylate (LA) compared with oral aspirin on prasugrel-inhibited platelets.
  
  
  RESULTS
  This was a prospective, randomized, single-center, open, 2-period crossover platelet function study conducted in 30 healthy volunteers. Subjects were randomly assigned to receive a loading dose of intravenous LA 450 mg plus oral prasugrel 60 mg or loading dose of aspirin 300 mg plus prasugrel 60 mg orally in a crossover fashion after a 2-week washout period between treatments. Platelet function was evaluated at baseline, 30 minutes, 1 h, 4 h, and 24 h using light transmission aggregometry and vasodilator-stimulated phosphoprotein phosphorylation. The primary end point of the study, inhibition of platelet aggregation after arachidonic acid 1.5 mmol/L at 30 minutes, was significantly higher in subjects treated with LA compared with aspirin: 85.3% versus 44.3%, respectively, P=0.003. This differential effect was observed at 1 hour (P=0.002) and 4 hours (P=0.048), but not at 24 hours. Subjects treated with LA presented less variability and faster and greater inhibition of platelet aggregation with arachidonic acid compared with aspirin.
  
  
  CONCLUSIONS
  The administration of intravenous LA resulted in a significant reduction of platelet reactivity compared with oral aspirin on prasugrel-inhibited platelets. Loading dose of LA achieves an earlier platelet inhibition and with less variability than aspirin.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT02243137.
authors.affiliation: From the Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain. dvivas@secardiologia.es.
authors.forename: David
authors.initials: D
authors.lastname: Vivas
authors.affiliation: From the Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
authors.forename: Agustín
authors.initials: A
authors.lastname: Martín
authors.affiliation: From the Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Bernardo
authors.affiliation: From the Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
authors.forename: María Aranzazu
authors.initials: MA
authors.lastname: Ortega-Pozzi
authors.affiliation: From the Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Tirado
authors.affiliation: From the Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Fernández
authors.affiliation: From the Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
authors.forename: Isidre
authors.initials: I
authors.lastname: Vilacosta
authors.affiliation: From the Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Núñez-Gil
authors.affiliation: From the Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Macaya
authors.affiliation: From the Cardiovascular Institute, San Carlos University Hospital, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Fernández-Ortiz
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D001792:Blood Platelets / Q000502:physiology; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride / Q000627:therapeutic use*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D010975:Platelet Aggregation Inhibitors; D000068799:Prasugrel Hydrochloride; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate
keywords: acute coronary syndrome; aspirin; lysine acetylsalicylate; platelet