2024 ESC guidelines on chronic coronary syndromes: what is new in pharmacotherapy?

The 2024 European Society of Cardiology Congress in London was set to unveil four highly anticipated guidelines dealing, specifically, with atrial fibrillation, chronic coronary syndromes (CCSs), elevated blood pressure/hypertension, and peripheral arterial/aortic diseases. The 2024 ESC guidelines for the management of CCS were particularly awaited,¹ given significant advances since the previous version in 2019.² The new guidelines introduce a more precise classification of CCS, based on the underlying mechanisms of myocardial ischaemia—from epicardial to microvascular, each of which may be structural, functional or both. They also progress towards a stratified and patient-centred approach to the diagnosis and treatment of the disease. Several updates on cardiovascular pharmacotherapy are of significant impact on clinical practice. The present Pharmapulse therefore summarizes the key pharmacotherapy updates introduced by the new CCS guidelines.

Antithrombotic therapy

A relevant update in antithrombotic therapy is represented by the class I, level of evidence (LoE) A recommendation for the use of clopidogrel monotherapy, 75 mg daily, as a safe and effective alternative to aspirin monotherapy, 75–100 mg daily, for the long-term treatment of chronic coronary syndrome (CCS) patients with a prior myocardial infarction (MI) or percutaneous coronary intervention (PCI), after an initial period of dual antiplatelet therapy (DAPT),¹ In such patients, aspirin or clopidogrel are equally recommended options.¹ The update is supported by the overall results of randomized controlled trials (RCTs) indicating that clopidogrel is associated with similar or better outcomes compared to aspirin monotherapy for the long-term prevention of adverse events in patients with stabilized MI or previous PCI.³ Because up to 30% of clopidogrel-treated patients show in vitro hyporesponsiveness to the drug, further investigations on the mechanisms of these findings are warranted.⁴ Aspirin monotherapy remains the standard of care for patients with previous coronary artery bypass graft (class I, LoE A) and has received an additional new recommendation for patients without prior MI or revascularization but with evidence of significant obstructive coronary artery disease (CAD) (class I, LoE B).¹

Another relevant update on antithrombotic therapy refers to DAPT duration following PCI. Although 6-month DAPT with aspirin and clopidogrel remains the standard of care after PCI for CCS, the 2024 guidelines also recommend DAPT discontinuation 1–3 months after the procedure—followed by single antiplatelet therapy—for two categories of patients: those at high bleeding risk, provided they are not at high ischaemic risk (class I, LoE A), and those neither at high bleeding nor at high ischaemic risk, in whom shortened DAPT may be considered (class IIb, LoE B). The update is supported by numerous medium- or large-sized RCTs consistently showing superior safety and comparable efficacy with 1–3 month compared to longer DAPT after PCI in CCS patients,^5,6 and by meta-analyses showing improved cardiovascular survival among high bleeding risk patients.⁷

Lipid lowering therapy

Among the recommendations for lipid-lowering, those on bempedoic acid are noteworthy, as this drug has been the focus of relevant studies in recent years.^8–10 In particular, bempedoic acid 180 mg daily has received a class I, LoE B recommendation for patients who are statin intolerant and do not achieve their low-density lipoprotein cholesterol goal on ezetimibe, and a class IIa, LoE C recommendation for patients who do not achieve this goal on a maximum tolerated dose of statin and ezetimibe.¹

Therapy for CCS patients with diabetes or high body mass index

Recommendations on the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors and of glucagon-like peptide 1 (GLP-1) receptor agonists have been updated in light of increasing evidence in patients with or without type 2 diabetes mellitus (T2DM).^11,12 Oral SGLT2 inhibitors and GLP-1 receptor agonists are recommended in patients with T2DM and CCS to reduce cardiovascular events, independently of baseline or target glycated haemoglobin (HbA1c) and independently of concomitant glucose-lowering medication (class I, LoE A). Importantly, in CCS patients without diabetes but with overweight or obesity (body mass index ≥27 kg/m²), the GLP-1 receptor agonist semaglutide (up to 2.4 mg once-weekly subcutaneously) is recommended (class IIa, LoE B) on the basis of a large RCT¹² where the drug demonstrated to reduce cardiovascular mortality, MI, or stroke.¹

Anti-inflammatory therapy

The efficacy and safety of colchicine in patients with stabilized or CCS has been investigated in recent years in multiple studies.^13,14 The overall evidence on low-dose colchicine (0.5 mg daily) has led the 2024 CCS guidelines to upgrade its use to reduce the risk of MI, stroke, and need for revascularization and to expand it to the totality of CCS patients with atherosclerotic CAD, given the broad inclusion criteria of investigated patients (class IIa, LoE A).¹ Previous ESC guidelines on cardiovascular disease prevention or on acute coronary syndromes recommended long-term low-dose colchicine in CAD patients with a class IIb, LoE A, particularly with insufficiently controlled traditional risk factors or with recurrent cardiovascular events despite optimal therapy.

Antianginal therapy

For symptomatic CCS patients, the 2024 CCS guidelines allow the immediate introduction of antianginal drug combinations and value the ‘diamond’ approach to guide the choice of synergistic vs. contraindicated combinations.¹⁵ The guidelines maintain a class I, LoE B for beta-receptor blockers, calcium-channel blockers, and short-acting nitrates.¹ As add-on therapy in patients with inadequate control of symptoms, while on treatment with a beta-receptor blocker and/or calcium channel blocker, or as part of initial treatment in properly selected patients, the guidelines adopt a class IIa, LoE B recommendation for ivabradine (in patients with left ventricular ejection fraction <40%), ranolazine or long-acting nitrates, and a class IIb, LoE B recommendation for nicorandil or trimetazidine.¹ Guidelines also recommend that anti-anginal therapy be tailored to each patient's haemodynamic profile (e.g. blood pressure, heart rate), comorbidities (especially heart failure), concomitant medications with potential drug interactions, and personal preferences. Treatment should also consider the underlying pathophysiology of myocardial ischaemia in each case and the availability of medications locally.

Conflicts of interest: F.A. reports receiving speaker or consultancy fees from Amgen, AstraZeneca, Bayer, Menarini, Novo Nordisk, and Servier, outside the present work. The remaining authors have nothing to declare.

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