Impact of Aspirin and Clopidogrel Hyporesponsiveness in Patients Treated With Drug-Eluting Stents: 2-Year Results of a Prospective, Multicenter Registry Study

• Published in: JACC. Cardiovascular interventions Vol. 10; no. 16; pp. 1607 - 1617
• Main Authors: Stuckey, Thomas D, Kirtane, Ajay J, Brodie, Bruce R, Witzenbichler, Bernhard, Litherland, Claire, Weisz, Giora, Rinaldi, Michael J, Neumann, Franz-Josef, Metzger, D Christopher, Henry, Timothy D, Cox, David A, Duffy, Peter L, Mazzaferri, Jr, Ernest L, Gurbel, Paul A, Mehran, Roxana, Généreux, Philippe, Ben-Yehuda, Ori, Simonton, Charles A, Stone, Gregg W
• Format: Journal Article
• Language: English
• Published: United States 28.08.2017
• Subjects: Aged; Aspirin - adverse effects; Aspirin - therapeutic use; Blood Platelets - drug effects; Blood Platelets - metabolism; Chi-Square Distribution; Clopidogrel; Coronary Thrombosis - etiology; Drug Resistance; Drug Therapy, Combination; Drug-Eluting Stents; Female; Germany; Hemorrhage - chemically induced; Humans; Kaplan-Meier Estimate; Male; Medication Adherence; Middle Aged; Myocardial Infarction - etiology; Percutaneous Coronary Intervention - adverse effects; Percutaneous Coronary Intervention - instrumentation; Percutaneous Coronary Intervention - mortality; Platelet Aggregation Inhibitors - adverse effects; Platelet Aggregation Inhibitors - therapeutic use; Platelet Function Tests; Proportional Hazards Models; Prospective Studies; Registries; Risk Factors; Ticlopidine - adverse effects; Ticlopidine - analogs & derivatives; Ticlopidine - therapeutic use; Time Factors; Treatment Outcome; United States; coronary artery disease; platelet reactivity; stent thrombosis; drug-eluting stent(s)
• ISSN: 1876-7605
• DOI: 10.1016/j.jcin.2017.05.059

In this analysis of 2-year outcomes in the ADAPT-DES (Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents) study, the authors sought to examine the independent associations between platelet reactivity to both aspirin and clopidogrel and subsequent outcomes. The relationship between platelet reactivity and long-term adverse events following implantation of drug-eluting stents (DES) has been incompletely characterized. The ADAPT-DES study was a multicenter registry of patients undergoing routine platelet function testing following percutaneous coronary intervention with DES. The primary study endpoint was definite or probable stent thrombosis (ST); other endpoints were all-cause mortality, myocardial infarction, and clinically relevant bleeding. A total of 8,582 patients were enrolled between 2008 and 2010; 46.3% of patients were on dual antiplatelet therapy at 2 years without discontinuation. At 2 years, definite or probable ST occurred in 92 patients (1.07%). In patients treated with dual antiplatelet therapy continuously for 2 years, high platelet reactivity on clopidogrel was independently associated with definite or probable ST (adjusted hazard ratio [HR]: 2.16; 95% confidence interval [CI]: 1.27 to 3.67; p = 0.003), myocardial infarction (adjusted HR: 1.35; 95% CI: 1.05 to 1.74; p = 0.02), freedom from clinically relevant bleeding (adjusted HR: 0.74; 95% CI: 0.62 to 0.90; p = 0.002), and all-cause mortality (adjusted HR: 1.36; 95% CI: 1.01 to 1.85; p = 0.04). Between years 1 and 2, high platelet reactivity was not associated with the very late ST and in patients on aspirin monotherapy, aspirin hyporesponsiveness was not associated with adverse outcomes. The present study confirms the strong relationship of high platelet reactivity on clopidogrel to 2-year ischemic and bleeding outcomes after DES. The majority of stent-related events occurred within the first year.