Dirk Sibbing, Dániel Aradi, Claudius Jacobshagen, Lisa Gross, Dietmar Trenk, Tobias Geisler, Martin Orban, Martin Hadamitzky, Béla Merkely, Róbert Gábor Kiss, András Komócsi, Csaba A Dézsi, Lesca Holdt, Stephan B Felix, Radoslaw Parma, Mariusz Klopotowski, Robert H G Schwinger, Johannes Rieber, Kurt Huber, Franz-Josef Neumann, Lukasz Koltowski, Julinda Mehilli, Zenon Huczek, Steffen Massberg, Zofia Parma, Maciej Lesiak, Anna Komosa, Michal Kowara, Bartosz Rymuza, Lukasz Malek, Daniel Aradi, Gábor Veress, András Döme Dézsi, Árpád Lux, Judit Papp, Andrea Kovács, Csaba András Dézsi, Sayour Amer, Zoltán Ruzsa, Szilárd Róna, Renáta Ili, Imre Ungi, Ferenc Nagy, Robert Zweiker, Gábor Tóth-Gayor, Paul Haller, Wolfgang von Scheidt, Andreas Blüthgen, Stefan Leggewie, Hans Ulrich Kreider-Stempfle, Thomas Remp, Kaffer Kara, Andreas Mügge, Alexander Wutzler, Stephan Fichtlscherer, Andreas M. Zeiher, Florian Seeger, Martin Hinterseer, Andreas König, Susanne Lederle, Frauke Czepluch, Lars Maier, Wolfgang Schillinger, Samuel Sossalla, Astrid Hummel, Stephan Felix, Mahir Karakas, Karsten Sydow, Tanja Rudolph, Marcel Halbach, Tommaso Gori, Thomas Münzel, Andreas May, Carsten-Manuel Gerstenberg, David Pilecky, Markus Deichstetter, Stefan Kääb, Anja Löw, Matthias Orban, Stefan Sattler, Sabine Deuschl, Daniel Teupser, Harald Mudra, Thomas Räder, Torsten Schütz, Felix Vahldiek, Dimitar Divchev, Hüseyin Ince, Christoph A Nienaber, Henning Radunski, Peter Boekstegers, Jan Horstkotte, Ralf Mueller, Karin Müller, Robert Schwinger, and Oliver Rasp
Summary 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 (p non-inferiority =0·0004; hazard ratio [HR] 0·81 [95% CI 0·62–1·06], p superiority =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%]; p non-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 Universitat Munchen, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.