The 2023 ESC guidelines encourage individualised antithrombotic treatment. Although the default strategy of 12 months of dual antiplatelet therapy (DAPT) with aspirin and a strong P2Y12 inhibitor (prasugrel or ticagrelor) remains unchanged, the guidelines offer guidance on specific clinical scenarios in which the default DAPT duration can be shortened (< 12 months), extended (> 12 months) or modified (de-escalation: i.e. switching from a strong P2Y12 inhibitor to clopidogrel).

In recent years, advancements in stent technology and intracoronary imaging-guided PCI have significantly reduced the risk of stent thrombosis. On the other hand, bleeding events carry a high risk of morbidity and mortality [11]. Therefore, emphasis should be shifted to tailoring treatment based on ischaemic and bleeding risk. The new guidelines advise that single antiplatelet therapy (SAPT) be considered after 3–6 months in patients who are event-free and are not at high ischaemic risk (class IIa, LoE A). If so, SAPT with a P2Y12 inhibitor should be preferred. In patients at high bleeding risk, a SAPT strategy may be considered even after 1 month (class IIb, LoE B). The LEGACY trial is currently evaluating the safety and efficacy of even earlier omittance of aspirin, i.e. immediate P2Y12 monotherapy, in NSTE-ACS patients [12].

In the elderly, especially those at high bleeding risk, the option of starting with clopidogrel instead of a strong P2Y12 inhibitor in order to reduce the bleeding risk may be considered (class IIb, LoE B).

Furthermore, P2Y12 inhibitor de-escalation in ACS patients may be considered as an alternative strategy to the default 12-month regimen, in order to reduce the risk of bleeding events. The guidelines do not recommend de-escalation in the first 30 days after an ACS due to a potentially increased risk of ischaemic events (class III, LoE B).

Interestingly, the POPULAR Genetics trial demonstrated that an early (in-hospital) CYP2C19 genotype-guided de-escalation strategy switching from ticagrelor to clopidogrel reduced bleeding while being non-inferior to standard treatment with respect to thrombotic events [13]. Moreover, this genotype-based strategy led to a significant cost reduction when applied in the Netherlands [14]. As CYP2C19 genotyping is now more widely used and available in many Dutch hospitals, efforts should be made to incorporate genotype-based strategies into clinical practice, especially for ACS patients at high bleeding risk.

In ACS patients with an indication for oral anticoagulation (non-vitamin‑K oral anticoagulant preferred to vitamin‑K antagonist), triple antithrombotic therapy (TAT) with the addition of aspirin and clopidogrel is recommended for up to 1 week, followed by 12 months of dual antithrombotic therapy (DAT; oral anticoagulant plus clopidogrel (class I, LoE A)). Generally, TAT is associated with a two- to threefold increase in bleeding risk [15] and therefore should be kept as short as possible. However, in patients with high ischaemic risk or other anatomical/procedural characteristics that outweigh the bleeding risk, TAT could be prolonged for up to 1 month (class IIa, LoE C). In patients with a very high risk of bleeding, maintenance DAT could be reduced to 6 months (class IIb, LoE B).

In medically managed ACS patients, current data support DAT over TAT, with a single antiplatelet agent (most commonly clopidogrel) for at least 6 months (class IIa, LoE B).

As illustrated by the previous scenarios, patient selection is key. Several risk scores have been developed to identify patients at high risk for bleeding or thrombotic events during follow-up. However, all risk scores are hampered by poor discriminatory abilities.

The 2023 guidelines recommend using either the ARC-HBR criteria or the PRECISE-DAPT (PREdicting bleeding Complications in patients undergoing Stent implantation and subsEquent Dual Anti Platelet Therapy) score for the assessment of bleeding risk. The presence of one major or two minor ARC-HBR risk factors indicates a high bleeding risk (Tab. 2; [6]). Of note is that the presence of multiple major risk factors is associated with a progressive increase in the bleeding risk. The PRECISE-DAPT is an easier-to-use tool with only five parameters (haemoglobin, age, leukocyte count, creatinine clearance and prior bleeding). A PRECISE-DAPT score of ≥ 25 is regarded as a high bleeding risk [16].

Thrombotic risk and (long-term) ischaemic risk are composed of both clinical (patient) characteristics and technical aspects related to the PCI or the coronary anatomy. High-risk features of stent-driven recurrent ischaemic events can be identified, such as prior stent thrombosis, treatment of bifurcation lesions or diffuse multivessel disease, especially in patients with diabetes. In addition, the DAPT score can be used, which has been validated in order to assess the benefit of DAPT continuation beyond 1 year after stenting [17].

As both bleeding and ischaemic risk are complex, we recommend assessing high bleeding risk and high ischaemic risk in a structured manner, using one of the above tools prior to discharge. In addition, the interventional cardiologist should take the leading role in highlighting any high-risk features of recurrent ischaemic events, related to the PCI procedure or coronary anatomy.

It is noteworthy that high bleeding risk and high ischaemic risk often overlap, as some risk factors (e.g. age, renal failure) pre-dispose to both bleeding and ischaemic risk. In patients with both high bleeding and ischaemic risk, prioritising the bleeding risk and thus abbreviating or de-escalating DAPT should generally be considered. Specifically, bleeding risk should be prioritised in frail older patients, in patients with anaemia or previous bleeding and in patients with active malignancy (all known strong predictors for bleeding).

Finally, the decision to continue DAPT beyond 1 year can be postponed to follow-up in the outpatient clinic. Patients who do not experience any bleeding events during the initial course of DAPT and have a high ischaemic risk should be considered for intensified antithrombotic therapy (DAPT continuation or aspirin plus very low-dose rivaroxaban) [18].