Antithrombotic therapy for secondary prevention in patients with acute coronary syndromes treated with percutaneous coronary intervention: options for personalization to reduce bleeding or ischaemic risks

Dual antiplatelet therapy (DAPT) is required to prevent atherothrombotic events in patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). The default DAPT strategy, namely a potent P2Y12 inhibitor combined with aspirin for 12 months, exposes many patients to excess bleeding risk. Over the past years, alternative antithrombotic regimens have been proposed to reduce bleeding (DAPT abbreviation or de-escalation) or ischaemic (prolonged dual antithrombotic therapy) events. Abbreviation or de-escalation of DAPT is supported by (i) multiple trials showing these strategies to significantly reduce bleeding, particularly for the 20-40% of patients classified as high bleeding risk (HBR); (ii) low prevalence of stent thrombosis and recurrent myocardial infarction beyond 1-3 months post-ACS with the latest generation of drug-eluting stents, and (iii) the recognition that HBR is far more prevalent than high ischaemic risk. Amongst patients at HBR, standard DAPT, in comparison to abbreviated or de-escalated DAPT, increases the net risk of major adverse events, even in the presence of high ischaemic risk. Conversely, amongst patients at high ischaemic risk, without HBR, prolonged dual antithrombotic therapy reduces longer-term thrombotic risk. Recognizing risk factors and assessing the magnitude of bleeding and ischaemic risks are essential. Since there are no ideal scoring systems to balance ischaemic and bleeding risks, and many overlap, focus should be on managing the risk most amenable to modification, namely bleeding, which should dominate the decision-making over ischaemic risk when choosing a DAPT regimen. This document provides practical advice regarding best practice for personalizing DAPT in patients with ACS undergoing PCI, with evidence-based clinical consensus statements on selecting the most appropriate antiplatelet strategy to optimize clinical outcomes.