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

• Published in: The Lancet (British edition) 2017-10, Vol.390 (10104), p.1747-1757
• Main Authors: Sibbing, Dirk, Aradi, Dániel, Gross, Lisa, Trenk, Dietmar, Geisler, Tobias, Orban, Martin, Hadamitzky, Martin, Merkely, Béla, Kiss, Róbert Gábor, Komócsi, András, Dézsi, Csaba A, Holdt, Lesca, Felix, Stephan B, Parma, Radoslaw, Schwinger, Robert H G, Rieber, Johannes, Huber, Kurt, Neumann, Franz-Josef, Koltowski, Lukasz, Mehilli, Julinda, Massberg, Steffen, Parma, Zofia, Lesiak, Maciej, Komosa, Anna, Huczek, Zenon, Kowara, Michal, Rymuza, Bartosz, Klopotowski, Mariusz, Veress, Gábor, Dézsi, András Döme, Lux, Árpád, Papp, Judit, Kovács, Andrea, Dézsi, Csaba András, Amer, Sayour, Róna, Szilárd, Ili, Renáta, Ungi, Imre, Zweiker, Robert, Tóth-Gayor, Gábor, Haller, Paul, von Scheidt, Wolfgang, Blüthgen, Andreas, Leggewie, Stefan, Kreider-Stempfle, Hans Ulrich, Kara, Kaffer, Mügge, Andreas, Fichtlscherer, Stephan, Zeiher, Andreas M., Seeger, Florian, Hinterseer, Martin, König, Andreas, Lederle, Susanne, Jacobshagen, Claudius, Czepluch, Frauke, Maier, Lars, Schillinger, Wolfgang, Sossalla, Samuel, Hummel, Astrid, Felix, Stephan, Karakas, Mahir, Sydow, Karsten, Rudolph, Tanja, Halbach, Marcel, Gori, Tommaso, Münzel, Thomas, May, Andreas, Gerstenberg, Carsten-Manuel, Pilecky, David, Deichstetter, Markus, Kääb, Stefan, Löw, Anja, Sattler, Stefan, Teupser, Daniel, Räder, Thomas, Schütz, Torsten, Vahldiek, Felix, Divchev, Dimitar, Ince, Hüseyin, Nienaber, Christoph A, Radunski, Henning, Boekstegers, Peter, Horstkotte, Jan, Mueller, Ralf, Schwinger, Robert, Rasp, Oliver
• Format: Article
• Language: English
• Subjects: Acute Coronary Syndrome - epidemiology; Acute Coronary Syndrome - therapy; Acute coronary syndromes; Angioplasty; Anticoagulants; Antiplatelet therapy; Biomarkers; Bleeding; Blood platelets; Cardiovascular diseases; Cerebral infarction; Clinical outcomes; Clinical trials; Clopidogrel; Consortia; Coronary vessels; Drug Administration Schedule; Drug Monitoring; Drug therapy; Europe - epidemiology; Evidence-based medicine; Female; Health risks; Heart attacks; Hemorrhage - chemically induced; Hemorrhage - epidemiology; Humans; Male; Middle Aged; Motivation; Myocardial infarction; Myocardial Infarction - epidemiology; Patients; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors - administration & dosage; Platelet Aggregation Inhibitors - adverse effects; Platelet Function Tests; Platelets; Prasugrel Hydrochloride - administration & dosage; Prasugrel Hydrochloride - adverse effects; Randomization; Stroke; Stroke - epidemiology; Test procedures; Thrombosis; Ticlopidine - administration & dosage; Ticlopidine - adverse effects; Ticlopidine - analogs & derivatives
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(17)32155-4

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). 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. 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 c