Francesca Maria Notarangelo1, Giuseppe Maglietta2, Paola Bevilacqua1, Marco Cereda3, Piera Angelica Merlini4, Giovanni Quinto Villani5, Paolo Moruzzi6, Giampiero Patrizi7, Guidantonio Malagoli Tagliazucchi8, Antonio Crocamo1, Angela Guidorossi1, Filippo Pigazzani1, Elisa Nicosia1, Giorgia Paoli1, Marco Bianchessi3, Mario Angelo Comelli9, Caterina Caminiti10, Diego Ardissino11. 1. Division of Cardiology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. 2. Division of Research and Innovation, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; Department of Statistics, Computer Science, Applications, Università di Firenze, Florence, Italy. 3. ST Microelectronics S.R.L., Agrate Brianza, Monza Brianza, Italy. 4. Division of Cardiology, Azienda Ospedaliera, Ospedale Niguarda Cà Granda, Milano, Italy. 5. Division of Cardiology, Azienda Territoriale di Piacenza, Piacenza, Italy. 6. Division of Cardiology, Azienda Territoriale di Parma, Fidenza, Italy. 7. Division of Cardiology, Azienda Territoriale di Modena, Carpi, Italy. 8. Division of Cardiology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; Division of Research and Innovation, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. 9. Department of Brain and Behavioural Science, Università di Pavia, Pavia, Italy. 10. Division of Research and Innovation, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. 11. Division of Cardiology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. Electronic address: dardissino@ao.pr.it.
Abstract
BACKGROUND: Although clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), its efficacy is hampered by interpatient response variability caused by genetic polymorphisms associated with clopidogrel's metabolism. OBJECTIVES: The goal of this study was to evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel, or ticagrelor) on the basis of a patient's genetic and clinical characteristics leads to better clinical outcomes compared with the standard of care, which bases the selection on clinical characteristics alone. METHODS:Patients hospitalized for ACS were randomly assigned to standard of care or the pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, and CYP2C19*17 using an ST Q3 system that provides data within 70 min at each patient's bedside. The patients were followed up for 12 ± 1 month for the primary composite endpoint of cardiovascular death and the first occurrence of nonfatal myocardial infarction, nonfatal stroke, and major bleeding defined according to Bleeding Academic Research Consortium type 3 to 5 criteria. RESULTS:After enrolling 888 patients, the study was prematurely stopped. Clopidogrel was used more frequently in the standard-of-care arm (50.7% vs. 43.3%), ticagrelor in the pharmacogenomic arm (42.6% vs. 32.7%; p = 0.02), and prasugrel was equally used in both arms. The primary endpoint occurred in 71 patients (15.9%) in the pharmacogenomic arm and in 114 (25.9%) in the standard-of-care arm (hazard ratio: 0.58; 95% confidence interval: 0.43 to 0.78; p < 0.001). CONCLUSIONS: A personalized approach to selecting antiplatelet therapy for patients with ACS may reduce ischemic and bleeding events. (Pharmacogenetics of Clopidogrel in Patients With Acute Coronary Syndromes [PHARMCLO]; NCT03347435).
RCT Entities:
BACKGROUND: Although clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), its efficacy is hampered by interpatient response variability caused by genetic polymorphisms associated with clopidogrel's metabolism. OBJECTIVES: The goal of this study was to evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel, or ticagrelor) on the basis of a patient's genetic and clinical characteristics leads to better clinical outcomes compared with the standard of care, which bases the selection on clinical characteristics alone. METHODS:Patients hospitalized for ACS were randomly assigned to standard of care or the pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, and CYP2C19*17 using an ST Q3 system that provides data within 70 min at each patient's bedside. The patients were followed up for 12 ± 1 month for the primary composite endpoint of cardiovascular death and the first occurrence of nonfatal myocardial infarction, nonfatal stroke, and major bleeding defined according to Bleeding Academic Research Consortium type 3 to 5 criteria. RESULTS: After enrolling 888 patients, the study was prematurely stopped. Clopidogrel was used more frequently in the standard-of-care arm (50.7% vs. 43.3%), ticagrelor in the pharmacogenomic arm (42.6% vs. 32.7%; p = 0.02), and prasugrel was equally used in both arms. The primary endpoint occurred in 71 patients (15.9%) in the pharmacogenomic arm and in 114 (25.9%) in the standard-of-care arm (hazard ratio: 0.58; 95% confidence interval: 0.43 to 0.78; p < 0.001). CONCLUSIONS: A personalized approach to selecting antiplatelet therapy for patients with ACS may reduce ischemic and bleeding events. (Pharmacogenetics of Clopidogrel in Patients With Acute Coronary Syndromes [PHARMCLO]; NCT03347435).
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