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  • Title: Prasugrel in Clopidogrel Nonresponders Undergoing Percutaneous Coronary Intervention: The RECLOSE-3 Study (REsponsiveness to CLOpidogrel and StEnt Thrombosis).
    Author: Valenti R, Marcucci R, Comito V, Marrani M, Cantini G, Migliorini A, Parodi G, Gensini GF, Abbate R, Antoniucci D.
    Journal: JACC Cardiovasc Interv; 2015 Oct; 8(12):1563-70. PubMed ID: 26386764.
    Abstract:
    OBJECTIVES: 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.
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