2023 ESC Guidelines on ACS: what is new in antithrombotic therapy?

Beyond late-breaking clinical trials, the presentation of the European Society of Cardiology (ESC) Guidelines has become a highly anticipated event at the annual ESC Congress. This year, the 2023 ESC Congress in Amsterdam staged the presentation of 4 Guidelines and a focused update. Among these, the 2023 ESC Guidelines for the management of acute coronary syndromes (ACS) were one of the most awaited, introducing important news in the diagnosis, classification, and treatment of ACS.1 Of note, these were the first ESC Guidelines to cover the full spectrum of ACS (unstable angina, non-ST-elevation ACS [NSTE-ACS], and ST-elevation myocardial infarction [STEMI]). When focusing on antithrombotic therapy, important changes emerge from the 2023 ACS Guidelines, compared to previous documents,2,3 with, at the same time, some reluctance towards paradigm shifts supported by randomized controlled trial (RCT) data.1 Hereinafter are some highlights: – Pre-treatment with a P2Y12 receptor inhibitor in STEMI patients has been downgraded from a class I, level of evidence (LoE) A to a class IIb, LoE B recommendation.1 This change is somewhat surprising, given no relevant additional evidence since previous STEMI guidelines.3 The change is presumably explained by the generally neutral results of ATLANTIC,4 and the increasing use of parenteral antiplatelet agents (e.g. cangrelor) in P2Y12 receptor inhibitor-naïve patients at the time of percutaneous coronary intervention (PCI).1–3 – While previous NSTE-ACS Guidelines described anticoagulation therapy in the early phase of ACS,2,5 the new 2023 Guidelines offer a broader and more detailed description of multiple anticoagulant options for STEMI and NSTE-ACS, identifying time from diagnosis to coronary angiography as a major determinant of type of anticoagulation for NSTE-ACS patients.1 – For patients with STEMI undergoing primary PCI, the bivalirudin recommendation has been upgraded from class IIb, LoE A, to class IIa, LoE A, in light of the recent BRIGHT-4 trial showing benefits of a 2–4 h high-dose post-PCI bivalirudin infusion compared to heparin.1,6 – Despite multiple RCT data supporting safety benefits of various antiplatelet de-escalation strategies in patients with and without high bleeding risk,7–9 12 months of dual-antiplatelet therapy (DAPT) with prasugrel or ticagrelor is still recommended as the default strategy for ACS patients (class I, LoE A). Shorter DAPT regimens are to be considered for ACS patients without ischaemic events and not at high-ischaemic risk after 3–6 months (class IIa, LoE A), while 1 month DAPT in patients at high bleeding risk (class IIb, LoE B) and de-escalation of P2Y12 inhibiting therapy (e.g. from prasugrel or ticagrelor to clopidogrel; class IIb, LoE A) may be considered to reduce the bleeding hazard.1 – Genotype- or platelet function-guided de-escalation of antiplatelet therapy is no longer listed as a possible beneficial strategy for ACS patients, despite RCT and meta-analytical data supporting improved safety and efficacy compared to unguided strategies.1,10 This omission represents a step back from cardiovascular precision medicine implementation, but may reflect the lack of widespread testing tools around the globe. – Beyond 12 months after an ACS, aspirin monotherapy is presented as the default therapy (class I, LoE A), with ‘P2Y12 inhibitor monotherapy’ as alternative to aspirin receiving a class IIb, LoE A, recommendation.1 While ‘P2Y12 inhibitor’ is subject to wide interpretation (i.e. clopidogrel vs. prasugrel or ticagrelor), the evidence from RCTs and meta-analyses supports a stronger recommendation for clopidogrel monotherapy in this setting.9 Conflict of interest: M.G. declares that he has received consulting fees or honoraria from Terumo, outside the present work. F.A. reports receiving speaker or consultancy fees from Amgen, AstraZeneca, Bayer, BMS/Pfizer, Daiichi, Sankyo, and Servier, outside the present work. P.S. has received speaker fees from AstraZeneca, Amgen, Axis TV, BMS, Les laboratoires Servier, Novartis, Novonordisk, Sanofi, and Vifor, outside the present work. The remaining authors have nothing to declare.