Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): A randomised, open-label, multicentre trial

Dirk Sibbing, Dániel Aradi, Claudius Jacobshagen, Lisa Gross, Dietmar Trenk, Tobias Geisler, Martin Orban, Martin Hadamitzky, B. Merkely, R. Kiss, A. Komócsi, Csaba A. Dézsi, Lesca Holdt, Stephan B. Felix, Radoslaw Parma, Mariusz Klopotowski, Robert H.G. Schwinger, Johannes Rieber, Kurt Huber, Franz Josef NeumannLukasz Koltowski, Julinda Mehilli, Zenon Huczek, Steffen Massberg

Research output: Article

150 Citations (Scopus)

Abstract

Background: Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). Methods: In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. Findings: Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (pnon-inferiority=0·0004; hazard ratio [HR] 0·81 [95% CI 0·62-1·06], psuperiority=0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; pnon-inferiority=0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0·82 [95% CI 0·59-1·13]; p=0·23). Interpretation: Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI. Funding: Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

Original languageEnglish
JournalThe Lancet
DOIs
Publication statusAccepted/In press - jan. 1 2017

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clopidogrel
Percutaneous Coronary Intervention
Acute Coronary Syndrome
Hemorrhage
Blood Platelets
Random Allocation
Control Groups
Therapeutics
Stroke
Myocardial Infarction
Intention to Treat Analysis
Platelet Aggregation Inhibitors
Research
Internet
Prasugrel Hydrochloride
Biomarkers
Maintenance
Research Personnel
Guidelines
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS) : A randomised, open-label, multicentre trial. / Sibbing, Dirk; Aradi, Dániel; Jacobshagen, Claudius; Gross, Lisa; Trenk, Dietmar; Geisler, Tobias; Orban, Martin; Hadamitzky, Martin; Merkely, B.; Kiss, R.; Komócsi, A.; Dézsi, Csaba A.; Holdt, Lesca; Felix, Stephan B.; Parma, Radoslaw; Klopotowski, Mariusz; Schwinger, Robert H.G.; Rieber, Johannes; Huber, Kurt; Neumann, Franz Josef; Koltowski, Lukasz; Mehilli, Julinda; Huczek, Zenon; Massberg, Steffen.

In: The Lancet, 01.01.2017.

Research output: Article

Sibbing, D, Aradi, D, Jacobshagen, C, Gross, L, Trenk, D, Geisler, T, Orban, M, Hadamitzky, M, Merkely, B, Kiss, R, Komócsi, A, Dézsi, CA, Holdt, L, Felix, SB, Parma, R, Klopotowski, M, Schwinger, RHG, Rieber, J, Huber, K, Neumann, FJ, Koltowski, L, Mehilli, J, Huczek, Z & Massberg, S 2017, 'Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): A randomised, open-label, multicentre trial', The Lancet. https://doi.org/10.1016/S0140-6736(17)32155-4
Sibbing, Dirk ; Aradi, Dániel ; Jacobshagen, Claudius ; Gross, Lisa ; Trenk, Dietmar ; Geisler, Tobias ; Orban, Martin ; Hadamitzky, Martin ; Merkely, B. ; Kiss, R. ; Komócsi, A. ; Dézsi, Csaba A. ; Holdt, Lesca ; Felix, Stephan B. ; Parma, Radoslaw ; Klopotowski, Mariusz ; Schwinger, Robert H.G. ; Rieber, Johannes ; Huber, Kurt ; Neumann, Franz Josef ; Koltowski, Lukasz ; Mehilli, Julinda ; Huczek, Zenon ; Massberg, Steffen. / Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS) : A randomised, open-label, multicentre trial. In: The Lancet. 2017.
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title = "Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): A randomised, open-label, multicentre trial",
abstract = "Background: Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). Methods: In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30{\%}). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. Findings: Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7{\%}) in the guided de-escalation group and in 118 patients (9{\%}) in the control group (pnon-inferiority=0·0004; hazard ratio [HR] 0·81 [95{\%} CI 0·62-1·06], psuperiority=0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3{\%}]) versus in the control group (42 patients [3{\%}]; pnon-inferiority=0·0115). There were 64 BARC 2 or higher bleeding events (5{\%}) in the de-escalation group versus 79 events (6{\%}) in the control group (HR 0·82 [95{\%} CI 0·59-1·13]; p=0·23). Interpretation: Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI. Funding: Klinikum der Universit{\"a}t M{\"u}nchen, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.",
author = "Dirk Sibbing and D{\'a}niel Aradi and Claudius Jacobshagen and Lisa Gross and Dietmar Trenk and Tobias Geisler and Martin Orban and Martin Hadamitzky and B. Merkely and R. Kiss and A. Kom{\'o}csi and D{\'e}zsi, {Csaba A.} and Lesca Holdt and Felix, {Stephan B.} and Radoslaw Parma and Mariusz Klopotowski and Schwinger, {Robert H.G.} and Johannes Rieber and Kurt Huber and Neumann, {Franz Josef} and Lukasz Koltowski and Julinda Mehilli and Zenon Huczek and Steffen Massberg",
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month = "1",
day = "1",
doi = "10.1016/S0140-6736(17)32155-4",
language = "English",
journal = "The Lancet",
issn = "0140-6736",
publisher = "Elsevier Limited",

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TY - JOUR

T1 - Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS)

T2 - A randomised, open-label, multicentre trial

AU - Sibbing, Dirk

AU - Aradi, Dániel

AU - Jacobshagen, Claudius

AU - Gross, Lisa

AU - Trenk, Dietmar

AU - Geisler, Tobias

AU - Orban, Martin

AU - Hadamitzky, Martin

AU - Merkely, B.

AU - Kiss, R.

AU - Komócsi, A.

AU - Dézsi, Csaba A.

AU - Holdt, Lesca

AU - Felix, Stephan B.

AU - Parma, Radoslaw

AU - Klopotowski, Mariusz

AU - Schwinger, Robert H.G.

AU - Rieber, Johannes

AU - Huber, Kurt

AU - Neumann, Franz Josef

AU - Koltowski, Lukasz

AU - Mehilli, Julinda

AU - Huczek, Zenon

AU - Massberg, Steffen

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background: Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). Methods: In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. Findings: Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (pnon-inferiority=0·0004; hazard ratio [HR] 0·81 [95% CI 0·62-1·06], psuperiority=0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; pnon-inferiority=0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0·82 [95% CI 0·59-1·13]; p=0·23). Interpretation: Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI. Funding: Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

AB - Background: Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). Methods: In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. Findings: Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (pnon-inferiority=0·0004; hazard ratio [HR] 0·81 [95% CI 0·62-1·06], psuperiority=0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; pnon-inferiority=0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0·82 [95% CI 0·59-1·13]; p=0·23). Interpretation: Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI. Funding: Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

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