High On-Treatment Platelet Reactivity After Prasugrel Loading Dose and Cardiovascular Events After Percutaneous Coronary Intervention in Acute Coronary Syndromes: Interventional Cardiology

• Published in: Journal of the American College of Cardiology 2011-07, Vol.58 (5), p.467-473
• Main Authors: Bonello, Laurent, Pansieri, Michel, Mancini, Julien, Bonello, Roland, Maillard, Luc, Barnay, Pierre, Rossi, Philippe, Ait-Mokhtar, Omar, Jouve, Bernard, Collet, Frederic, Peyre, Jean Pascal, Wittenberg, Olivier, de Labriolle, Axel, Camilleri, Elise, Cheneau, Edouard, Cabassome, Elma, Dignat-George, Francoise, Camoin-Jau, Laurence, Paganelli, Franck
• Format: Article
• Language: English
• ISSN: 0735-1097
• DOI: 10.1016/j.jacc.2011.04.017

Objectives The aim of this study was to investigate the relationship between platelet reactivity (PR) after a loading dose (LD) of prasugrel and thrombotic events. Background Post-treatment PR has been shown to be strongly associated with the occurrence of major adverse cardiac events (MACE) after percutaneous coronary intervention (PCI) in the clopidogrel era. Prasugrel is a new P2Y12-adenosine diphosphate receptor with a higher potency on PR. Methods A prospective multicenter study included patients who underwent successful PCI for acute coronary syndromes and received prasugrel therapy. Vasodilator-stimulated phosphoprotein (VASP) index was measured after the prasugrel LD. High on-treatment PR was defined as a VASP index greater than or equal to 50%. MACE included cardiovascular death, myocardial infarction, and definite stent thrombosis at 1 month. Results Three hundred one patients were enrolled. The mean VASP index after 60 mg of prasugrel was 34.3 plus or minus 23.1%. High on-treatment PR was observed in 76 patients (25.2%). Patients experiencing thrombotic events after PCI had significantly higher VASP indexes compared with those free of events (64.4 plus or minus 14.4% vs. 33.4 plus or minus 22.7%; range: 51% to 64% and 5% to 47.6%, respectively; p = 0.001). Kaplan-Meier analysis comparing good responders and patients with high on-treatment PR demonstrated a significantly higher rate of MACE in patients with suboptimal PR inhibition (log-rank p < 0.001). Receiver-operating characteristic curve analysis found a cutoff value of 53.5% of the VASP index to predict thrombotic events at 1 month (r = 0.86, p < 0.001). Patients with minor or major Thrombolysis In Myocardial Infarction unrelated to coronary artery bypass grafting bleeding and those without had similar VASP indexes (30 plus or minus 17.8% vs. 34.3 plus or minus 23%, p = 0.70). Conclusions Despite the use of prasugrel, a significant number of patients undergoing PCI in the setting of acute coronary syndromes do not achieve optimal PR inhibition. Such patients have a higher risk for MACE after PCI.