title: High on-treatment platelet reactivity after prasugrel loading dose and cardiovascular events after percutaneous coronary intervention in acute coronary syndromes.
abstract: OBJECTIVE
  The aim of this study was to investigate the relationship between platelet reactivity (PR) after a loading dose (LD) of prasugrel and thrombotic events.
  
  
  BACKGROUND
  Post-treatment PR has been shown to be strongly associated with the occurrence of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in the clopidogrel era. Prasugrel is a new P2Y(12)-adenosine diphosphate receptor with a higher potency on PR.
  
  
  METHODS
  A prospective multicenter study included patients who underwent successful PCI for acute coronary syndromes and received prasugrel therapy. Vasodilator-stimulated phosphoprotein (VASP) index was measured after the prasugrel LD. High on-treatment PR was defined as a VASP index ≥50%. MACE included cardiovascular death, myocardial infarction, and definite stent thrombosis at 1 month.
  
  
  RESULTS
  Three hundred one patients were enrolled. The mean VASP index after 60 mg of prasugrel was 34.3 ± 23.1%. High on-treatment PR was observed in 76 patients (25.2%). Patients experiencing thrombotic events after PCI had significantly higher VASP indexes compared with those free of events (64.4 ± 14.4% vs. 33.4 ± 22.7%; range: 51% to 64% and 5% to 47.6%, respectively; p = 0.001). Kaplan-Meier analysis comparing good responders and patients with high on-treatment PR demonstrated a significantly higher rate of MACE in patients with suboptimal PR inhibition (log-rank p < 0.001). Receiver-operating characteristic curve analysis found a cutoff value of 53.5% of the VASP index to predict thrombotic events at 1 month (r = 0.86, p < 0.001). Patients with minor or major Thrombolysis In Myocardial Infarction unrelated to coronary artery bypass grafting bleeding and those without had similar VASP indexes (30 ± 17.8% vs. 34.3 ± 23%, p = 0.70).
  
  
  CONCLUSIONS
  Despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition. Such patients have a higher risk for MACE after PCI.
authors.affiliation: Département de Cardiologie, Hôpital Universitaire Nord, Faculté de Médecine, Chemin des Bourrely, Marseille, France. laurentbonello@yahoo.fr
authors.forename: Laurent
authors.initials: L
authors.lastname: Bonello
authors.forename: Michel
authors.initials: M
authors.lastname: Pansieri
authors.forename: Julien
authors.initials: J
authors.lastname: Mancini
authors.forename: Roland
authors.initials: R
authors.lastname: Bonello
authors.forename: Luc
authors.initials: L
authors.lastname: Maillard
authors.forename: Pierre
authors.initials: P
authors.lastname: Barnay
authors.forename: Philippe
authors.initials: P
authors.lastname: Rossi
authors.forename: Omar
authors.initials: O
authors.lastname: Ait-Mokhtar
authors.forename: Bernard
authors.initials: B
authors.lastname: Jouve
authors.forename: Frederic
authors.initials: F
authors.lastname: Collet
authors.forename: Jean Pascal
authors.initials: JP
authors.lastname: Peyre
authors.forename: Olivier
authors.initials: O
authors.lastname: Wittenberg
authors.forename: Axel
authors.initials: A
authors.lastname: de Labriolle
authors.forename: Elise
authors.initials: E
authors.lastname: Camilleri
authors.forename: Edouard
authors.initials: E
authors.lastname: Cheneau
authors.forename: Elma
authors.initials: E
authors.lastname: Cabassome
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin-Jau
authors.forename: Franck
authors.initials: F
authors.lastname: Paganelli
mesh_terms: D054058:Acute Coronary Syndrome / Q000628:therapy*; D015906:Angioplasty, Balloon, Coronary; D001792:Blood Platelets / Q000378:metabolism*; D003328:Coronary Thrombosis / Q000453:epidemiology; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D010750:Phosphoproteins / Q000378:metabolism*; D010879:Piperazines / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D011237:Predictive Value of Tests; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D015607:Stents; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D010750:Phosphoproteins; D010879:Piperazines; D058921:Purinergic P2Y Receptor Antagonists; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride