Quantifying Ischemic Risk After Percutaneous Coronary Intervention Attributable to High Platelet Reactivity on Clopidogrel (From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study) - 29/08/17

Doi : 10.1016/j.amjcard.2017.06.019

Björn Redfors, MD, PhD ^a, Ori Ben-Yehuda, MD ^a,^b, Sheng-Hsuan Lin, MD, MS, ScD ^c, Ariel Furer, MD ^a,^d, Ajay J. Kirtane, MD, SM ^a,^b, Bernhard Witzenbichler, MD ^e, Giora Weisz, MD ^a,^f, Thomas D. Stuckey, MD ^g, Akiko Maehara, MD ^a,^b, Philippe Généreux, MD ^a,^h,ⁱ, Gennaro Giustino, MD ^j, Michael J. Rinaldi, MD ^k, Franz-Josef Neumann, MD ^l, D. Christopher Metzger, MD ^m, Timothy D. Henry, MD ^n,^o, David A. Cox, MD ^p, Peter L. Duffy, MD ^q, Ernest L. Mazzaferri, MD ^r, Girma Minalu Ayele, PhD ^a, Roxana Mehran, MD ^a,^j, Gary S. Mintz, MD ^a, Gregg W. Stone, MD ^a,^b,^*
^a Clinical Trials Center, Cardiovascular Research Foundation, New York, New York
^b NewYork-Presbyterian Hospital/Columbia University Medical Center, New York, New York
^c Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York
^d Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
^e Helios Amper-Klinikum, Dachau, Germany
^f Montefiore Medical Center, Bronx, New York
^g LeBauer-Brodie Center for Cardiovascular Research and Education/Cone Health, Greensboro, North Carolina
^h Hôpital du Sacré-Coeur de Montréal, Montréal, Québec, Canada
ⁱ Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, New Jersey
^j Icahn School of Medicine at Mount Sinai, New York, New York
^k Sanger Heart & Vascular Institute/Carolinas HealthCare System, Charlotte, North Carolina
^l Universitäts-Herzzentrum Freiburg Bad Krozingen, Bad Krozingen, Germany
^m Wellmont CVA Heart Institute, Kingsport, Tennessee
ⁿ Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, Minnesota
^o Cedars-Sinai Heart Institute, Los Angeles, California
^p Lehigh Valley Health Network, Allentown, Pennsylvania
^q Reid Heart Center, FirstHealth of the Carolinas, Pinehurst, North Carolina
^r The Ohio State University Wexner Medical Center, Columbus, Ohio

^*Corresponding author: Tel: (646) 434-4134; fax: (646) 434-4715.

Abstract

Patients at high risk of thrombotic events after percutaneous coronary intervention (PCI) may potentially benefit from intensified antiplatelet therapy. However, more potent antiplatelet therapy would be expected to only overcome risk that is mediated by high platelet reactivity (PR). We used mediation analysis to determine the contribution of residual PR to the 2-year risk of major adverse cardiac events (MACE; the composite of cardiac death, myocardial infarction, or stent thrombosis) associated with clinical risk factors after PCI with drug-eluting stents (DES) in 8,374 patients from the prospective, multicenter Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents (ADAPT-DES) registry. Residual PR on clopidogrel, as measured by the VerifyNow P2Y12 point-of-care assay, was included as a continuous linear mediator variable in Cox proportional hazards regression. Among 7 factors independently associated with 2-year MACE, residual PR partly mediated the effect of diabetes (13.4% attributable risk), anemia (22.9% attributable risk), and acute coronary syndromes (7.3% attributable risk). A PR-mediated effect inversely affected the MACE risk associated with smoking (10.4% attributable risk). The increased ischemic risk of chronic kidney disease, multivessel disease, and previous myocardial infarction were not mediated by residual PR. In conclusion, high residual PR mediates little or none of the increased 2-year MACE risk associated with baseline risk factors in patients treated with clopidogrel after successful PCI with DES. Intensifying antiplatelet therapy is therefore unlikely to substantially mitigate the excess ischemic risk from these variables.

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	Sources of funding: 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, and Accumetrics.
	See page 922 for disclosure information.

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Vol 120 - N° 6

P. 917-923 - septembre 2017 Retour au numéro

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Quantifying Ischemic Risk After Percutaneous Coronary Intervention Attributable to High Platelet Reactivity on Clopidogrel (From the Assessment of Dual Antiplatelet Therapy with Drug-Eluting Stents Study) - 29/08/17

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