Gennaro Giustino1, Björn Redfors2, Ajay J Kirtane3, Roxana Mehran1, George D Dangas1, Bernhard Witzenbichler4, Franz-Josef Neumann5, Giora Weisz6, Philippe Généreux7, Akiko Maehara3, Thomas McAndrew2, Serdar Farhan8, Michael J Rinaldi9, D Christopher Metzger10, Timothy D Henry11, David A Cox12, Peter L Duffy13, Ernest L Mazzaferri14, Bruce R Brodie15, Thomas D Stuckey15, Paul Gurbel16, Ori Ben-Yehuda3, Gregg W Stone17. 1. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Cardiovascular Research Foundation, New York, New York. 2. Cardiovascular Research Foundation, New York, New York. 3. Cardiovascular Research Foundation, New York, New York; Division of Cardiology, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York. 4. Helios Amper-Klinikum, Dachau, Germany. 5. Universitats-Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, Germany. 6. Cardiovascular Research Foundation, New York, New York; Division of Cardiology, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York; Shaare Zedek Medical Center, Jerusalem, Israel. 7. Cardiovascular Research Foundation, New York, New York; Division of Cardiology, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York; Hôpital du Sacré-Coeur de Montréal, Université de Montréal, Montréal, Quebec, Canada. 8. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. 9. Sanger Heart and Vascular Institute/Carolinas HealthCare System, Charlotte, North Carolina. 10. Wellmont CVA Heart Institute, Kingsport, Tennessee. 11. Cedars-Sinai Heart Institute, Los Angeles, California; Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota. 12. Lehigh Valley Health Network, Allentown, Pennsylvania. 13. Reid Heart Center, First Health of the Carolinas, Pinehurst, North Carolina. 14. The Ohio State University Wexner Medical Center, Columbus, Ohio. 15. LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, North Carolina. 16. Inova Heart and Vascular Institute, Falls Church, Virginia. 17. Cardiovascular Research Foundation, New York, New York; Division of Cardiology, NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York. Electronic address: gstone@crf.org.
Abstract
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).
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).