• Ajay J Kirtane, Puja B Parikh, Thomas D Stuckey, Ke Xu, Bernhard Witzenbichler, Giora Weisz, Michael J Rinaldi, Franz-Josef Neumann, D Christopher Metzger, Timothy D Henry, David A Cox, Peter L Duffy, Bruce R Brodie, Ernest L Mazzaferri, Rupa Parvataneni, Akiko Maehara, Philippe Généreux, Roxana Mehran, and Gregg W Stone.
• Division of Cardiology, Columbia University/NewYork-Presbyterian Hospital, New York, New York; Cardiovascular Research Foundation, New York, New York. Electronic address: akirtane@columbia.edu.
• JACC Cardiovasc Interv. 2015 Dec 28; 8 (15): 1978-1987.

ObjectivesThis study sought to determine whether there is an ideal level of platelet reactivity (PR) to optimize safety and efficacy within the large multicenter ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents) study of 8,582 patients receiving successful drug-eluting stent implantation.BackgroundPatients with high PR on clopidogrel have a greater incidence of adverse ischemic events after stent implantation, whereas low PR may increase bleeding. Due to limited sample size, previous studies have not been able to adjust for differences in baseline characteristics that may confound the relationship of PR and outcomes.MethodsIn the ADAPT-DES study, routine platelet function testing (VerifyNow) was performed following clopidogrel loading. To characterize the independent association between PR and clinical events, patients were stratified into quintiles of P2Y12 reaction units (PRU).ResultsThe PRU medians of the 5 quintiles were 57, 130, 187, 244, and 317 (most to least inhibited). There was a monotonic association between successively higher PRU quintiles and stent thrombosis, whereas for clinically relevant bleeding, the greatest risk occurred in the lowest PRU quintile, with similar risks across the 4 higher quintiles. These relationships remained significant in fully adjusted multivariable analyses (adjusted hazard ratio [HR] for stent thrombosis in Q5 versus Q1: 2.32; 95% confidence interval [CI]: 1.17 to 4.59; p = 0.02; adjusted HR for clinically relevant bleeding in Q5 versus Q1: 0.61; 95% CI: 0.47 to 0.77; p < 0.001). However, there were no significant independent associations between the level of PRU and mortality.ConclusionsIn this large observational study, increasing PRU was associated with a monotonic increase in stent thrombosis, whereas bleeding risk was confined to the lowest PRU quintile, suggesting an optimal therapeutic window of platelet inhibition at moderately inhibited PRU. However, there was no demonstrable threshold effect for PRU and mortality in adjusted analyses, perhaps due to the offsetting impact of bleeding and ischemia across the spectrum of platelet inhibition. (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents [ADAPT-DES]; NCT00638794).Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

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