Research in context
Evidence before this study
A potent P2Y12 inhibitor-based dual antiplatelet therapy is recommended for up to 1 year in patients with acute coronary syndrome receiving percutaneous coronary intervention (PCI). De-escalation of the antiplatelet regimen is commonly performed in clinical practice but is not yet implemented in guidelines due to a scarcity of clear clinical evidence. We searched PubMed on Aug 1, 2020, for articles published in English with the search terms “dual antiplatelet therapy”, “de-escalation”, “switching antiplatelet therapy”, “percutaneous coronary intervention”, and “acute coronary syndrome”. Our search identified only a few randomised studies that focused on clinical outcomes. In the TWILIGHT study, de-escalation to ticagrelor monotherapy as compared with aspirin–ticagrelor dual therapy showed a lower incidence of clinical events, especially major bleeding. In the TROPICAL ACS study, de-escalation guided by platelet function testing was non-inferior to standard treatment with prasugrel. However, the multistep protocol of this strategy would be cumbersome and impractical in real-world practice.
Added value of this study
HOST-REDUCE POLYTECH-ACS is the first randomised trial to investigate a prasugrel-based dose de-escalation strategy in patients with acute coronary syndrome receiving PCI. In 2338 patients, prasugrel dose de-escalation was non-inferior to conventional therapy in preventing net adverse clinical events (a composite of all-cause death, non-fatal myocardial infarction, stent thrombosis, clinically driven revascularisation, stroke, and Bleeding Academic Research Consortium grade ≥2 bleeding). Subsequent equality testing showed that de-escalation significantly reduced the occurrence of the primary endpoint. The main driver of the difference was a reduction in bleeding, without an increase in ischaemic outcomes. Post-hoc analysis also showed that the beneficial effect of prasugrel de-escalation was consistent in various subgroups without any significant interaction. By showing non-inferiority of prasugrel de-escalation during the chronic maintenance phase, our trial provides important justification for dose reduction of prasugrel in east Asian patients with acute coronary syndrome receiving PCI.
Implications of all the available evidence
In patients with acute coronary syndrome receiving PCI who are indicated to take the full dose of prasugrel, de-escalation of prasugrel dose to 5 mg might be a feasible alternative strategy during chronic maintenance therapy, especially when the risk of bleeding is a concern.