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).

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.

• Authors: Björn Redfors, Ori Ben-Yehuda, Sheng-Hsuan Lin, Ariel Furer, Ajay J Kirtane, Bernhard Witzenbichler, Giora Weisz, Thomas D Stuckey, Akiko Maehara, Philippe Généreux, Gennaro Giustino, Michael J Rinaldi, Franz-Josef Neumann, D Christopher Metzger, Timothy D Henry, David A Cox, Peter L Duffy, Ernest L Mazzaferri Jr, Girma Minalu Ayele, Roxana Mehran, Gary S Mintz, Gregg W Stone
• Journal: The American journal of cardiology (Am J Cardiol) Vol. 120 Issue 6 Pg. 917-923 (Sep 15 2017) ISSN: 1879-1913 [Electronic] United States
• PMID: 28754568 (Publication Type: Journal Article, Multicenter Study)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Platelet Aggregation Inhibitors
• Clopidogrel
• Ticlopidine
• Aspirin

Topics

• Aspirin (administration & dosage)
• Clopidogrel
• Coronary Artery Disease (surgery)
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Drug-Eluting Stents
• Female
• Germany (epidemiology)
• Graft Occlusion, Vascular (blood, epidemiology, etiology)
• Humans
• Incidence
• Israel (epidemiology)
• Male
• Middle Aged
• Percutaneous Coronary Intervention (adverse effects)
• Platelet Activation (drug effects)
• Platelet Aggregation Inhibitors (administration & dosage)
• Prognosis
• Prospective Studies
• Quebec (epidemiology)
• Registries
• Risk Assessment (methods)
• Risk Factors
• Survival Rate (trends)
• Ticlopidine (administration & dosage, analogs & derivatives)
• United States (epidemiology)