Dániel Aradi1,2, Lisa Gross3,4, Dietmar Trenk5, Tobias Geisler6, Béla Merkely2, Róbert Gábor Kiss7, András Komócsi8, Csaba András Dézsi9, Zoltán Ruzsa2, Imre Ungi10, Konstantinos D Rizas3,4, Andreas E May11, Andreas Mügge12, Andreas M Zeiher13, Lesca Holdt14, Kurt Huber15, Franz-Josef Neumann5, Lukasz Koltowski16, Zenon Huczek16, Martin Hadamitzky17, Steffen Massberg3,4, Dirk Sibbing3,4. 1. Department of Active Cardiology, Heart Centre Balatonfüred and Heart and Vascular Centre, Semmelweis University Budapest, 2 Gyógy Tér, Balatonfüred, Hungary. 2. Department of Cardiology, Heart and Vascular Centre, Semmelweis University Budapest, Budapest, Hungary. 3. Department of Cardiology, LMU München, Munich, Germany. 4. Partner Site Munich Heart Alliance, DZHK (German Center for Cardiovascular Research), Munich, Germany. 5. Department of Cardiology and Angiology II, University Heart Centre Freiburg-Bad Krozingen, Bad Krozingen, Germany. 6. Department of Cardiology and Cardiovascular Disease, University Hospital Tübingen, Tübingen, Germany. 7. Department of Cardiology, Military Hospital, Budapest, Hungary. 8. Department of Interventional Cardiology, Heart Institute, University of Pécs, Pécs, Hungary. 9. Department of Cardiology, Petz Aladár County Hospital Győr, Győr, Hungary. 10. Department of Cardiology, University of Szeged, Szeged, Hungary. 11. Department of Cardiology, Innere Medizin I, Klinikum Memmingen, Memmingen, Germany. 12. Department of Cardiology, Katholisches Klinikum Bochum, St. Josef Hospital, Bochum, Germany. 13. Department of Cardiology, Universitätsklinikum Frankfurt, Frankfurt/Main, Germany. 14. Institute of Laboratory Medicine, University Hospital, LMU Munich, Munich, Germany. 15. 3rd Medical Department, Cardiology and Intensive Care Medicine, Sigmund Freud Private University, Medical School, Wien, Austria. 16. 1 Department of Cardiology, Medical University of Warsaw, Warsaw, Poland. 17. Department of Radiology and Nuclear Medicine, Deutsches Herzzentrum München, Munich, Germany.
Abstract
AIMS: The value of platelet function testing (PFT) in predicting clinical outcomes and guiding P2Y12-inhibitor treatment is uncertain. In a pre-specified sub-study of the TROPICAL-ACS trial, we assessed ischaemic and bleeding risks according to high platelet reactivity (HPR) and low platelet reactivity (LPR) to ADP in patients receiving uniformprasugrel vs. PFT-guided clopidogrel or prasugrel. METHODS AND RESULTS:Acute coronary syndrome patients with PFT done 14 days after hospital discharge were included with prior randomization to uniform prasugrel for 12 months (control group, no treatment modification) vs. early de-escalation from prasugrel to clopidogrel and PFT-guided maintenance treatment (HPR: switch-back to prasugrel, non-HPR: clopidogrel). The composite ischaemic endpoint included cardiovascular death, myocardial infarction, or stroke, while key safety outcome was Bleeding Academic Research Consortium (BARC) 2-5 bleeding, from PFT until 12 months. We identified 2527 patients with PFT results available: 1266 were randomized to the guided and 1261 to the control group. Before treatment adjustment, HPR was more prevalent in the guided group (40% vs. 15%), while LPR was more common in control patients (27% vs. 11%). Compared to control patients without HPR on prasugrel (n = 1073), similar outcomes were observed in guided patients kept on clopidogrel [n = 755, hazard ratio (HR): 1.06 (0.57-1.95), P = 0.86] and also in patients with HPR on clopidogrel switched to prasugrel [n = 511, HR: 0.96 (0.47-1.96), P = 0.91]. In contrast, HPR on prasugrel was associated with a higher risk for ischaemic events in control patients [n = 188, HR: 2.16 (1.01-4.65), P = 0.049]. Low platelet reactivity was an independent predictor of bleeding [HR: 1.74 (1.18-2.56), P = 0.005], without interaction (Pint = 0.76) between study groups. CONCLUSION: Based on this substudy of a randomized trial, selecting prasugrel or clopidogrel based on PFT resulted in similar ischaemic outcomes as uniform prasugrel therapy without HPR. Although infrequent, HPR on prasugrel was associated with increased risk of ischaemic events. Low platelet reactivity was a strong and independent predictor of bleeding both on prasugrel and clopidogrel. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIMS: The value of platelet function testing (PFT) in predicting clinical outcomes and guiding P2Y12-inhibitor treatment is uncertain. In a pre-specified sub-study of the TROPICAL-ACS trial, we assessed ischaemic and bleeding risks according to high platelet reactivity (HPR) and low platelet reactivity (LPR) to ADP in patients receiving uniform prasugrel vs. PFT-guided clopidogrel or prasugrel. METHODS AND RESULTS:Acute coronary syndromepatients with PFT done 14 days after hospital discharge were included with prior randomization to uniform prasugrel for 12 months (control group, no treatment modification) vs. early de-escalation from prasugrel to clopidogrel and PFT-guided maintenance treatment (HPR: switch-back to prasugrel, non-HPR: clopidogrel). The composite ischaemic endpoint included cardiovascular death, myocardial infarction, or stroke, while key safety outcome was Bleeding Academic Research Consortium (BARC) 2-5 bleeding, from PFT until 12 months. We identified 2527 patients with PFT results available: 1266 were randomized to the guided and 1261 to the control group. Before treatment adjustment, HPR was more prevalent in the guided group (40% vs. 15%), while LPR was more common in control patients (27% vs. 11%). Compared to control patients without HPR on prasugrel (n = 1073), similar outcomes were observed in guided patients kept on clopidogrel [n = 755, hazard ratio (HR): 1.06 (0.57-1.95), P = 0.86] and also in patients with HPR on clopidogrel switched to prasugrel [n = 511, HR: 0.96 (0.47-1.96), P = 0.91]. In contrast, HPR on prasugrel was associated with a higher risk for ischaemic events in control patients [n = 188, HR: 2.16 (1.01-4.65), P = 0.049]. Low platelet reactivity was an independent predictor of bleeding [HR: 1.74 (1.18-2.56), P = 0.005], without interaction (Pint = 0.76) between study groups. CONCLUSION: Based on this substudy of a randomized trial, selecting prasugrel or clopidogrel based on PFT resulted in similar ischaemic outcomes as uniform prasugrel therapy without HPR. Although infrequent, HPR on prasugrel was associated with increased risk of ischaemic events. Low platelet reactivity was a strong and independent predictor of bleeding both on prasugrel and clopidogrel. Published on behalf of the European Society of Cardiology. All rights reserved.
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