Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization
Authors: Stefano Savonitto, Luca A. Ferri, Luigi Piatti, Daniele Grosseto, Giancarlo Piovaccari, Nuccia Morici, Irene Bossi, Paolo Sganzerla, Giovanni Tortorella, Michele Cacucci, Maurizio Ferrario, Ernesto Murena, Girolamo Sibilio, Stefano Tondi, Anna Toso, Sergio Bongioanni, Amelia Ravera, Elena Corrada, Matteo Mariani, Leonardo Di Ascenzo, A. Sonia Petronio, Claudio Cavallini, Giancarlo Vitrella, Renata Rogacka, Roberto Antonicelli, Bruno M. Cesana, Leonardo De Luca, Filippo Ottani, Giuseppe De Luca, Federico Piscione, Nadia Moffa, Stefano De Servi, Leonardo Bolognese, Francesco Bovenzi, Giuseppe Steffenino, Ignazio Santilli, Giorgio Bassanelli, Alice Sacco, Federico Canziani, Marco Ferri, Emilia Lo Jacono, Umberto Canosi, Giuseppe Fornaro, Mario Leoncini, Maria Rosa Conte, Rosario Farina, Catia Stefanin, Francesco Di Pede, Piersilvio Chella, M. Chiara Nardoni, Paola Tamburrini, Bruno Trimarco, Gennaro Galasso, Raffaele Elia, Leonardo Bolognese, Simone Grotti, Francesco Bovenzi, Lucia Borrelli, Corrado Tamburino, Piera Capranzano, Bruno Francaviglia, Carlo Campana, Roberto Bonatti, Alessandro Martinoni, Fabio Abate, Sebastian Coscarelli, Paolo Rubartelli, Giovanni Q. Villani, Roberta Rossini
Journal: Circulation (2018)

Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding.In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg.Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78-1.30; P=0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13-1.00; P=0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85-3.16; P=0.18).The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial.URL: https://www.clinicaltrials.gov. Unique identifier: NCT01777503.