Author + information
- Received November 15, 2017
- Revision received January 22, 2018
- Accepted January 24, 2018
- Published online July 2, 2018.
- Gennaro Giustino, MDa,b,∗,
- Björn Redfors, MD, PhDb,∗,
- Ajay J. Kirtane, MD, SMb,c,
- Roxana Mehran, MDa,b,
- George D. Dangas, MD, PhDa,b,
- Bernhard Witzenbichler, MDd,
- Franz-Josef Neumann, MDe,
- Giora Weisz, MDb,c,f,
- Philippe Généreux, MDb,c,g,
- Akiko Maehara, MDb,c,
- Thomas McAndrew, PhDb,
- Serdar Farhan, MDa,
- Michael J. Rinaldi, MDh,
- D. Christopher Metzger, MDi,
- Timothy D. Henry, MDj,k,
- David A. Cox, MDl,
- Peter L. Duffy, MDm,
- Ernest L. Mazzaferri Jr., MDn,
- Bruce R. Brodie, MDo,
- Thomas D. Stuckey, MDo,
- Paul Gurbel, MDp,
- Ori Ben-Yehuda, MDb,c and
- Gregg W. Stone, MDb,c,∗ ()
- aThe Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- bCardiovascular Research Foundation, New York, New York
- cDivision of Cardiology, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York
- dHelios Amper-Klinikum, Dachau, Germany
- eUniversitats-Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, Germany
- fShaare Zedek Medical Center, Jerusalem, Israel
- gHôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada
- hSanger Heart and Vascular Institute/Carolinas HealthCare System, Charlotte, North Carolina
- iWellmont CVA Heart Institute, Kingsport, Tennessee
- jCedars-Sinai Heart Institute, Los Angeles, California
- kMinneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota
- lLehigh Valley Health Network, Allentown, Pennsylvania
- mReid Heart Center, First Health of the Carolinas, Pinehurst, North Carolina
- nThe Ohio State University Wexner Medical Center, Columbus, Ohio
- oLeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, North Carolina
- pInova Heart and Vascular Institute, Falls Church, Virginia
- ↵∗Address for correspondence:
Dr. Gregg W. Stone, Columbia University Medical Center, Cardiovascular Research Foundation, 161 Ft. Washington Avenue, Herbert Irving Pavilion, 6th Floor, New York, New York 10032.
Objectives The authors sought to investigate the association between P2Y12 reaction units (PRU) and the risk of ischemic stroke (IS) after successful coronary drug-eluting stents (DES) implantation.
Background The association between platelet reactivity on clopidogrel and the risk for ischemic cerebrovascular events remains unclear.
Methods Incidence, predictors, and prognostic impact of IS were evaluated among patients enrolled in the multicenter, prospective ADAPT-DES (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents) study. By protocol, patients were maintained on aspirin for 2 years and clopidogrel for at least 1 year. Baseline platelet reactivity on clopidogrel and aspirin were assessed by means of VerifyNow point-of-care assay after successful DES implantation.
Results Among 8,582 patients enrolled, 68 (0.8%) had an IS during 2-year follow-up. Across the spectrum of PRU, rates of IS were progressively greater as patients transitioned from the lowest quintile of PRU (more P2Y12 receptor inhibition; 2-year rate of 0.51%) to the highest quintile of PRU (less P2Y12 receptor inhibition; 2-year rate of 1.34%; adjusted p = 0.04). PRU >208 was independently associated with higher risk of IS at 2 years (adjusted hazard ratio 1.81; 95% confidence interval 1.08 to 3.04; p = 0.03). The association between higher PRU and risk for IS was also consistent in patients with versus without high CHA2DS2-VASc score (pinteraction = 0.30) and in those on or off oral anticoagulation at discharge (pinteraction = 0.99). Occurrence of IS was strongly associated with increased risk of all-cause mortality at 2 years (adjusted HR: 4.16; 95% CI: 1.95 to 8.87; p < 0.0001).
Conclusions Higher PRU was associated with increased risk of IS after coronary DES implantation. Ensuring adequate platelet P2Y12 receptor inhibition may reduce the risk of IS in this patient population. (Assessment of Dual AntiPlatelet Therapy With Drug Eluting Stents [ADAPT-DES]; NCT00638794)
↵∗ Drs. Giustino and Redfors contributed equally to this work.
Dr. Kirtane has received institutional grants from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, Cardiovascular Systems Inc., CathWorks, Eli Lilly, Siemens, Philips, ReCor Medical, and Spectranetics. Drs. Mehran and Dangas have received institutional research grant support from Eli Lilly/Daiichi-Sankyo, Bristol-Myers Squibb, AstraZeneca, The Medicines Company, OrbusNeich, Bayer, CSL Behring, Abbott Laboratories, Watermark Research Partners, Novartis Pharmaceuticals, Medtronic, AUM Cardiovascular, Inc., and Beth Israel Deaconess Medical Center; have served on executive committees for Janssen Pharmaceuticals and Osprey Medical Inc.; have served on data safety monitoring boards for Watermark Research Partners; have been consultants for Medscape, The Medicines Company, Boston Scientific, Merck & Company, Cardiovascular Systems Inc., Sanofi USA, LLC, Shanghai BraccoSine Pharmaceutical Corp., and AstraZeneca; and hold equity in Claret Medical Inc. and Elixir Medical Corporation. Dr. Witzenbichler has been a consultant/advisory board member for Volcano. Dr. Weisz has served as an advisory board member for AngioSlide, AstraZeneca, Corindus, Filterlex, M.I. Medical Incentive, Medtronic, Medivizor, TriSol, and Vectorious. Dr. Généreux has received speaker fees from Abbott Vascular, Medtronic, Edwards Lifesciences, Cardiovascular System Inc., and Tryton Medical Inc.; has received research grants from Boston Scientific and Cardiovascular System Inc.; has been a consultant for Cardiovascular System Inc., Medtronic, Edwards Lifesciences, Soundbite Medical Solutions Inc., Pi-Cardia, SARANAS, and SIG.NUM; and is a shareholder in Soundbite Medical Solutions Inc. and SIG.NUM. Dr. Maehara has received institutional grant support from Boston Scientific, St. Jude Medical, and Abbott Vascular; has been a consultant for Boston Scientific and OCT Medical Imaging Inc.; and has received speaker fees from St. Jude Medical. Dr. Rinaldi has served on advisory boards for Abbott Vascular, Boston Scientific, Cordis, and Edwards Lifesciences. Dr. Metzger has received symposium honoraria from Abbott Vascular and Boston Scientific. Dr. Henry has served on scientific advisory boards for Abbott Vascular, Boston Scientific, and The Medicines Company; and has been on the steering committee for the TRANSLATE study sponsored by Eli Lilly and Daiichi-Sankyo. Dr. Cox has been a consultant for Abbott Vascular, Boston Scientific, and Medtronic. Dr. Duffy has been a consultant/speaker for Philips Medical/Volcano. Dr. Stuckey has served on an advisory board for Boston Scientific; and has received speakers honoraria from Boston Scientific and Eli Lilly/Daiichi-Sankyo. Dr. Gurbel has been a consultant for Daiichi-Sankyo, Bayer, AstraZeneca, Merck, Medtronic, CSL, Janssen, New Haven Pharmaceuticals, Boehringer Ingelheim, Amgen, Duke Clinical Research Institute, Idorsia, Ionis, and Haemonetics; has received grants from the National Institutes of Health, Daiichi-Sankyo, CSL, AstraZeneca, Harvard Clinical Research Institute, Haemonetics, Coramed, Merck, Medicure, Abbott, Sinnowa, and the Duke Clinical Research Institute; has received lecture fees including service on speakers bureaus from AstraZeneca, Daiichi-Sankyo, Medicure, and Merck; holds stock or stock options from Merck, Medtronic, and Pfizer; and holds patents in the area of personalized antiplatelet therapy and interventional cardiology. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 15, 2017.
- Revision received January 22, 2018.
- Accepted January 24, 2018.
- 2018 American College of Cardiology Foundation
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