Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel: A pre-specified exploratory analysis from the TROPICAL-ACS trial

Dániel Aradi, Lisa Gross, Dietmar Trenk, Tobias Geisler, Bcrossed D.Signla Merkely, R. Kiss, A. Komócsi, Csaba András DCrossed D'Signzsi, 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 HadamitzkySteffen Massberg, Dirk Sibbing

Research output: Article

8 Citations (Scopus)

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 uniform prasugrel vs. PFT-guided clopidogrel or prasugrel.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. 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.

Original languageEnglish
Pages (from-to)1942-1951
Number of pages10
JournalEuropean heart journal
Volume40
Issue number24
DOIs
Publication statusPublished - jún. 21 2019

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clopidogrel
Acute Coronary Syndrome
Blood Platelets
Hemorrhage
Prasugrel Hydrochloride

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel : A pre-specified exploratory analysis from the TROPICAL-ACS trial. / Aradi, Dániel; Gross, Lisa; Trenk, Dietmar; Geisler, Tobias; Merkely, Bcrossed D.Signla; Kiss, R.; Komócsi, A.; DCrossed D'Signzsi, Csaba András; Ruzsa, Zoltán; Ungi, Imre; Rizas, Konstantinos D.; May, Andreas E.; Mügge, Andreas; Zeiher, Andreas M.; Holdt, Lesca; Huber, Kurt; Neumann, Franz Josef; Koltowski, Lukasz; Huczek, Zenon; Hadamitzky, Martin; Massberg, Steffen; Sibbing, Dirk.

In: European heart journal, Vol. 40, No. 24, 21.06.2019, p. 1942-1951.

Research output: Article

Aradi, D, Gross, L, Trenk, D, Geisler, T, Merkely, BDS, Kiss, R, Komócsi, A, DCrossed D'Signzsi, CA, Ruzsa, Z, Ungi, I, Rizas, KD, May, AE, Mügge, A, Zeiher, AM, Holdt, L, Huber, K, Neumann, FJ, Koltowski, L, Huczek, Z, Hadamitzky, M, Massberg, S & Sibbing, D 2019, 'Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel: A pre-specified exploratory analysis from the TROPICAL-ACS trial', European heart journal, vol. 40, no. 24, pp. 1942-1951. https://doi.org/10.1093/eurheartj/ehz202
Aradi, Dániel ; Gross, Lisa ; Trenk, Dietmar ; Geisler, Tobias ; Merkely, Bcrossed D.Signla ; Kiss, R. ; Komócsi, A. ; DCrossed D'Signzsi, Csaba András ; Ruzsa, Zoltán ; Ungi, Imre ; Rizas, Konstantinos D. ; May, Andreas E. ; Mügge, Andreas ; Zeiher, Andreas M. ; Holdt, Lesca ; Huber, Kurt ; Neumann, Franz Josef ; Koltowski, Lukasz ; Huczek, Zenon ; Hadamitzky, Martin ; Massberg, Steffen ; Sibbing, Dirk. / Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel : A pre-specified exploratory analysis from the TROPICAL-ACS trial. In: European heart journal. 2019 ; Vol. 40, No. 24. pp. 1942-1951.
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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 uniform prasugrel vs. PFT-guided clopidogrel or prasugrel.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. 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.",
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TY - JOUR

T1 - Platelet reactivity and clinical outcomes in acute coronary syndrome patients treated with prasugrel and clopidogrel

T2 - A pre-specified exploratory analysis from the TROPICAL-ACS trial

AU - Aradi, Dániel

AU - Gross, Lisa

AU - Trenk, Dietmar

AU - Geisler, Tobias

AU - Merkely, Bcrossed D.Signla

AU - Kiss, R.

AU - Komócsi, A.

AU - DCrossed D'Signzsi, Csaba András

AU - Ruzsa, Zoltán

AU - Ungi, Imre

AU - Rizas, Konstantinos D.

AU - May, Andreas E.

AU - Mügge, Andreas

AU - Zeiher, Andreas M.

AU - Holdt, Lesca

AU - Huber, Kurt

AU - Neumann, Franz Josef

AU - Koltowski, Lukasz

AU - Huczek, Zenon

AU - Hadamitzky, Martin

AU - Massberg, Steffen

AU - Sibbing, Dirk

PY - 2019/6/21

Y1 - 2019/6/21

N2 - 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.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. 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.

AB - 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.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. 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.

KW - Acute coronary syndrome

KW - Clopidogrel

KW - High platelet reactivity

KW - Low platelet reactivity

KW - Platelet function testing

KW - Prasugrel

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