Title

Is There an Ideal Level of Platelet P2Y12-Receptor Inhibition in Patients Undergoing Percutaneous Coronary Intervention?: "Window" Analysis From the ADAPT-DES Study (Assessment of Dual AntiPlatelet Therapy With Drug-Eluting Stents).

Authors

Ajay J. Kirtane, Columbia University/NewYork-Presbyterian Hospital, New York, New YorkFollow
Puj B. Parikh, Columbia University/NewYork-Presbyterian Hospital, New York, New York
Thomas D. Stuckey, LeBauer Cardiovascular Research Foundation/Moses Cone Hospital, Greensboro, North Carolina
Ke Xu, Cardiovascular Research Foundation, New York, New YorkFollow
Bernhard Witzenbichler, Amper Kliniken AG, Dachau, GermanyFollow
Giora Weisz, Columbia University/NewYork-Presbyterian Hospital, New York, New York; CardiovascularFollow
Michael J Rinaldi, Sanger Heart and Vascular Institute/Carolinas HealthCare System, Charlotte, North Carolina
Franz-Josef Neumann, Universitäts-Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, GermanyFollow
D Christopher Metzger, Wellmont CVA Heart Institute, Kingsport, Tennessee
Timothy D. Henry, Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis
David A. Cox MD, Lehigh Valley Health NetworkFollow
Peter L. Duffy, FirstHealth of the Carolinas, Pinehurst, North CarolinaFollow
Bruce R. Brodie, LeBauer Cardiovascular Research Foundation/Moses Cone Hospital, Greensboro, North Carolin
Ernest L. Mazzaferri, The Ohio State University, Columbus, Ohi
Rupa Parvataneni, Cardiovascular Research Foundation, New York, New YorkFollow
Akiko Maehara, Division of Cardiology, Columbia University/NewYork-Presbyterian Hospital, New York, New York
Philippe Généreux, Columbia University/NewYork-Presbyterian Hospital, New York, New York
Roxana Mehran, Cardiovascular Research Foundation, New York, New York
Gregg W Stone, Columbia University/NewYork-Presbyterian Hospital, New York, New York

Publication/Presentation Date

12-28-2015

Abstract

OBJECTIVES: This 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.

BACKGROUND: Patients 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.

METHODS: In 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).

RESULTS: The 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.

CONCLUSIONS: In 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).

Volume

8

Issue

15

First Page

1978

Last Page

1987

ISSN

1876-7605

Disciplines

Medical Sciences | Medicine and Health Sciences

PubMedID

26738669

Department(s)

Department of Medicine, Department of Medicine Faculty

Document Type

Article