• Dániel Aradi, Lisa Gross, Dietmar Trenk, Tobias Geisler, Béla Merkely, Róbert Gábor Kiss, András Komócsi, Csaba András Dézsi, Zoltán Ruzsa, Imre Ungi, Konstantinos D Rizas, Andreas E May, Andreas Mügge, Andreas M Zeiher, Lesca Holdt, Kurt Huber, Franz-Josef Neumann, Lukasz Koltowski, Zenon Huczek, Martin Hadamitzky, Steffen Massberg, and Dirk Sibbing.
• Department of Active Cardiology, Heart Centre Balatonfüred and Heart and Vascular Centre, Semmelweis University Budapest, 2 Gyógy Tér, Balatonfüred, Hungary.
• Eur. Heart J. 2019 Jun 21; 40 (24): 1942-1951.

AimsThe 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 ResultsAcute 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.ConclusionBased 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. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.

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