Author + information
- Received October 23, 2014
- Revision received July 28, 2015
- Accepted August 17, 2015
- Published online December 28, 2015.
- Ajay J. Kirtane, MD, SM∗,†∗ (, )
- Puja B. Parikh, MD∗,
- Thomas D. Stuckey, MD‡,
- Ke Xu, PhD†,
- Bernhard Witzenbichler, MD§,
- Giora Weisz, MD∗,†,‖,
- Michael J. Rinaldi, MD¶,
- Franz-Josef Neumann, MD#,
- D. Christopher Metzger, MD∗∗,
- Timothy D. Henry, MD††,‡‡,
- David A. Cox, MD§§,
- Peter L. Duffy, MD, MMM‖‖,
- Bruce R. Brodie, MD‡,
- Ernest L. Mazzaferri Jr., MD¶¶,
- Rupa Parvataneni, MS†,
- Akiko Maehara, MD∗,†,
- Philippe Généreux, MD∗,†,##,
- Roxana Mehran, MD†∗∗∗ and
- Gregg W. Stone, MD∗,†
- ∗Division of Cardiology, Columbia University/NewYork-Presbyterian Hospital, New York, New York
- †Cardiovascular Research Foundation, New York, New York
- ‡LeBauer Cardiovascular Research Foundation/Moses Cone Hospital, Greensboro, North Carolina
- §Amper Kliniken AG, Dachau, Germany
- ‖Department of Cardiology, Shaare Zedek Medical Center, Jerusalem, Israel
- ¶Sanger Heart and Vascular Institute/Carolinas HealthCare System, Charlotte, North Carolina
- #Department of Cardiology, Universitäts-Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, Germany
- ∗∗Wellmont CVA Heart Institute, Kingsport, Tennessee
- ††Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota
- ‡‡Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
- §§Department of Medicine, Lehigh Valley Health Network, Allentown, Pennsylvania
- ‖‖Reid Heart Center, FirstHealth of the Carolinas, Pinehurst, North Carolina
- ¶¶Department of Medicine, The Ohio State University, Columbus, Ohio
- ##Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada
- ∗∗∗Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
- ↵∗Reprint requests and correspondence:
Dr. Ajay J. Kirtane, Columbia University Medical Center/NewYork-Presbyterian Hospital, 161 Fort Washington Avenue, 6th Floor, New York, New York 10032.
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)
The ADAPT-DES study was sponsored by the Cardiovascular Research Foundation, with funding provided by Boston Scientific, Abbott Vascular, Medtronic, Cordis, Biosensors, The Medicines Company, Daiichi-Sankyo, Eli Lilly, Volcano Corp., and Accumetrics. Dr. Kirtane has received institutional research grants to Columbia University from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude Medical, Vascular Dynamics, and Eli Lilly. Dr. Stuckey has served on the advisory board for Boston Scientific; and has received speaker honoraria from Boston Scientific and Eli Lilly/Daiichi-Sankyo. Dr. Witzenbichler has served as a consultant to Volcano Corp.; and has received lecture fees from Volcano Corp., Elixir Med, and Atrium Med. Dr. Weisz has served as a consultant to InfraReDx. Dr. Rinaldi has served as a consultant to Abbott Vascular, Boston Scientific, St. Jude Medical, and Volcano Corp. Dr. Metzger has served as a consultant to Abbott Vascular, Cordis, IDEV Technologies, Medtronic, and Volcano Corp. Dr. Henry has served on the scientific advisory boards for Abbott Vascular, Boston Scientific, and The Medicines Company; and has served on the Steering Committee for TRANSLATE, which is sponsored by Eli Lilly and Company/Daiichi Sankyo. Dr. Cox has served as a consultant to Abbott Vascular and Boston Scientific. Dr. Duffy has received speaker honoraria from Volcano Corp. Dr. Maehara has received grant support from Boston Scientific; and has served as a consultant for Boston Scientific. Dr. Mehran has received institutional research grant support from AstraZeneca, The Medicines Company, Bristol-Myers Squibb/Sanofi, Eli Lilly and Company/Daiichi-Sankyo, Regado Biosciences, and STENTYS; has served as a consultant to Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, CSL Behring, Janssen Pharmaceuticals, Maya Medical, Merck & Co., and Regado Biosciences; has served on the advisory boards of Covidien, Janssen Pharmaceuticals, Merck & Co., and Sanofi. Dr. Stone has served as a consultant to Volcano Corp., InfraReDx, Boston Scientific, and Eli Lilly and Company/Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 23, 2014.
- Revision received July 28, 2015.
- Accepted August 17, 2015.
- 2015 American College of Cardiology Foundation