title: A randomised trial on platelet function-guided de-escalation of antiplatelet treatment in ACS patients undergoing PCI. Rationale and design of the Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary Syndromes (TROPICAL-ACS) Trial.
abstract: Outcomes of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) have been significantly improved with the use of potent P2Y12receptor inhibitors like prasugrel. While most of the ischaemic risk reduction for prasugrel versus clopidogrel was demonstrated in the early treatment period, the risk of bleeding became particularly prominent during the chronic course of therapy. It may therefore be a valid approach to substitute prasugrel for clopidogrel in the early phase of chronic antiplatelet treatment after PCI. In the Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial, we aim to compare standard prasugrel therapy with a de-escalating antiplatelet treatment approach guided by platelet function testing (PFT). The study is an investigator-initiated European multicentre, randomised clinical trial in biomarker-positive ACS patients after successful PCI. Two thousand six hundred patients will be randomised prior to hospital discharge in a 1:1 fashion to either receive standard prasugrel therapy (control group) or de-escalating therapy (one-week prasugrel followed by one-week clopidogrel and PFT-guided maintenance therapy from day 14 after hospital discharge, monitoring group). Patients of the monitoring group with high on-clopidogrel platelet reactivity (HPR) based on Multiplate analyzer testing (HPR: ≥ 46U per consensus definition) will be switched back to prasugrel, whereas those without HPR (<46 U) will continue clopidogrel treatment. The overall study treatment duration will be one year in both groups. The primary endpoint of the study is net clinical benefit (combined incidence of cardiovascular death, myocardial infarction, stroke and bleeding ≥ grade 2 according to BARC criteria) one-year after randomisation. TROPICAL-ACS is the first large-scale, randomised controlled trial assessing the clinical value of a PFT-guided de-escalation of antiplatelet treatment in biomarker positive ACS patients undergoing PCI.
authors.affiliation: Prof. Dr. med. Dirk Sibbing, Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität München, Marchioninistr. 15, 81377 Munich, Germany, E-mail: dirk.sibbing@med.uni-muenchen.de or dirk@sibbing.net.
authors.forename: Dirk
authors.initials: D
authors.lastname: Sibbing
authors.forename: Dániel
authors.initials: D
authors.lastname: Aradi
authors.forename: Claudius
authors.initials: C
authors.lastname: Jacobshagen
authors.forename: Lisa
authors.initials: L
authors.lastname: Gross
authors.forename: Dietmar
authors.initials: D
authors.lastname: Trenk
authors.forename: Tobias
authors.initials: T
authors.lastname: Geisler
authors.forename: Martin
authors.initials: M
authors.lastname: Orban
authors.forename: Tommaso
authors.initials: T
authors.lastname: Gori
authors.forename: Martin
authors.initials: M
authors.lastname: Hadamitzky
authors.forename: Béla
authors.initials: B
authors.lastname: Merkely
authors.forename: Róbert Gábor
authors.initials: RG
authors.lastname: Kiss
authors.forename: András
authors.initials: A
authors.lastname: Komócsi
authors.forename: Csaba A
authors.initials: CA
authors.lastname: Dézsi
authors.forename: Andreas
authors.initials: A
authors.lastname: Thalmeier
authors.forename: Anja
authors.initials: A
authors.lastname: Löw
authors.forename: Lesca
authors.initials: L
authors.lastname: Holdt
authors.forename: Daniel
authors.initials: D
authors.lastname: Teupser
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Ince
authors.forename: Stephan B
authors.initials: SB
authors.lastname: Felix
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Parma
authors.forename: Lukasz
authors.initials: L
authors.lastname: Malek
authors.forename: Jan
authors.initials: J
authors.lastname: Horstkotte
authors.forename: Monika
authors.initials: M
authors.lastname: Baylacher
authors.forename: Robert
authors.initials: R
authors.lastname: Schwinger
authors.forename: Johannes
authors.initials: J
authors.lastname: Rieber
authors.forename: Harald
authors.initials: H
authors.lastname: Mudra
authors.forename: Jörg
authors.initials: J
authors.lastname: Hausleiter
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
authors.forename: Lukasz
authors.initials: L
authors.lastname: Koltowski
authors.forename: Zenon
authors.initials: Z
authors.lastname: Huczek
authors.forename: Julinda
authors.initials: J
authors.lastname: Mehilli
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002985:Clinical Protocols; D000077144:Clopidogrel; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005060:Europe; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage* / Q000009:adverse effects; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D012107:Research Design; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
keywords: Acute coronary syndrome; antiplatelet drugs; platelets