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

Background:

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.

Methods:

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.

Results:

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).

Conclusions:

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.

Clinical Trial Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01777503.