title: Prasugrel in Clopidogrel Nonresponders Undergoing Percutaneous Coronary Intervention: The RECLOSE-3 Study (REsponsiveness to CLOpidogrel and StEnt Thrombosis).
abstract: OBJECTIVE
  This study sought to investigate the efficacy of prasugrel compared with clopidogrel in clopidogrel nonresponders.
  
  
  BACKGROUND
  Clopidogrel nonresponsiveness is a strong marker of the risk of cardiac death and stent thrombosis after a percutaneous coronary intervention (PCI). It is unknown whether clopidogrel nonresponsiveness is a nonmodifiable risk factor or whether prasugrel with more potent and predictable platelet inhibition as measured by ex vivo techniques is associated with a positive effect on clinical outcome.
  
  
  METHODS
  The RECLOSE-3 (REsponsiveness to CLOpidogrel and StEnt thrombosis) study screened clopidogrel nonresponders after a 600-mg loading dose of clopidogrel. Clopidogrel nonresponders switched to prasugrel (10 mg/day) the day of the PCI, and an adenosine diphosphate (ADP) test (10 μmol/l of ADP) was performed 6 days after the PCI. The primary endpoint was 2-year cardiac mortality. Patient outcome was compared with the RECLOSE-2-ACS study.
  
  
  RESULTS
  We screened 1,550 patients, of whom 302 were clopidogrel nonresponders. The result of the ADP test was 77.6 ± 6.2%. After switching to prasugrel, the ADP test result decreased to 47.1 ± 16.8%. The 2-year cardiac mortality rate was 4% in the RECLOSE-3 study and 9.7% in nonresponders of the RECLOSE-2-ACS study (p = 0.007). The definite and probable stent thrombosis rates were 0.7% and 4.4%, respectively (p = 0.004). On multivariable analysis, prasugrel treatment was related to the risk of 2-year cardiac death (hazard ratio: 0.32, p = 0.036).
  
  
  CONCLUSIONS
  Clopidogrel nonresponsiveness can be overcome by prasugrel (10 mg/day), and optimal platelet aggregation inhibition on prasugrel treatment is associated with a low rate of long-term cardiac mortality and stent thrombosis.
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Valenti
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Marcucci
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Comito
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Marrani
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Cantini
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Migliorini
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Parodi
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Gensini
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.affiliation: Department of Cardiology, Careggi Hospital, Florence, Italy. Electronic address: david.antoniucci@virgilio.it.
authors.forename: David
authors.initials: D
authors.lastname: Antoniucci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D003328:Coronary Thrombosis / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D004351:Drug Resistance; D057915:Drug Substitution; D005260:Female; D065386:Historically Controlled Study; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation* / Q000401:mortality; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D015607:Stents; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: clopidogrel; prasugrel; stent thrombosis