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 Universitat Munchen, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.
