ESC’s 2024 CCS Guidelines Embrace New Data, Smooth Old Tensions

LONDON, England—The European Society of Cardiology (ESC) has issued new guidelines for the treatment of patients with chronic coronary syndromes (CCS).

The guidelines, presented at ESC Congress 2024 and published in the European Heart Journal, were a massive undertaking as they merge and update two older documents: the 2018 guidelines for myocardial revascularization and 2019 guidelines for the diagnosis and management of chronic coronary syndromes.

Chaired by Christiaan Vrints, MD, PhD (University of Antwerp, Belgium), and Felicita Andreotti, MD, PhD (Fondazione Policlinico Universitario Gemelli IRCCS, Rome, Italy), the latest CCS guidelines, which run 123 pages with 1,211 references, have been arranged to include tables highlighting what’s new and what’s changed.

Right off the top, there’s an updated definition of chronic coronary syndromes, with ESC experts defining it as a “range of clinical presentations or syndromes that arise due to structural and/or functional alterations related to chronic diseases of the coronary arteries and/or microcirculation.” Clinical presentations include asymptomatic patients with abnormal anatomic or functional test results, angina or equivalent with no obstructive CAD, stress-induced angina or equivalent with obstructive CAD, stabilized disease after ACS, PCI, or CABG, and LV dysfunction or heart failure of ischemic origin.

“Since 2019, there’s been a paradigm shift in our understanding of the pathophysiology of myocardial ischemia and chronic coronary syndromes,” said Vrints during an ESC presentation highlighting the recommendations. “We have moved from a very simple concept that a proximal stenosis is causing myocardial ischemia to a more complex and dynamic concept.”

Importantly, the new guidelines are endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) and provide some closure on a controversy that has simmered for years: the best way to revascularize a patient with left main CAD.

“I'm really proud to say that we have finally reestablished a European framework for myocardial revascularization again given the fact that the EACTS withdrew support from [the left main] recommendations back in 2019,” Milan Milojevic, MD, PhD (Dedinje Cardiovascular Institute, Belgrade, Serbia), who served as the EACTS representative on the writing committee, told TCTMD. “Finally, after 5 years, we have reestablished a framework and this is, I think, a very positive development.”

Some Closure

In CCS patients at low surgical risk with a significant left main coronary stenosis, CABG is the preferred approach over medical therapy to improve survival (class I, level of evidence [LOE] A) and over PCI to lower the risk of spontaneous MI and repeat revascularization (class I, LOE A). In CCS patients with a low SYNTAX score (≤ 22), PCI can be alternative to CABG if complete revascularization can be achieved (class I, LOE A) because it’s noninferior to CABG surgery for all-cause mortality and is less invasive, according to the guidelines.

Under the 2018 guidelines, PCI was a class I (LOE A) recommendation for patients with left main CAD and a low SYNTAX score and a IIa (LOE A) recommendation for those with an intermediate score, but that was challenged by the surgical community following the 5-year EXCEL results showing higher mortality risks with PCI. Breaking ranks, one EXCEL investigator said the trial was largely biased in favor of PCI, and there were allegations of trial misconduct, namely not reporting some endpoints that placed PCI in an unfavorable light.

Although strongly disputed by the EXCEL leadership group, EACTS formally withdrew their support for the left main section of the 2018 revascularization guidelines and the ESC launched a review of the left main recommendations, which was conducted by a joint ESC/EACTS task force. After an independent meta-analysis found no significant difference in the risk of death following revascularization with PCI or surgery at 5 years, the task force recommended downgrading PCI to a class IIa (LOE A) recommendation for stable patients with left main CAD and a low or intermediate SYNTAX score.

In chronic coronary syndromes, paraphrasing Hamlet, there is more between heaven and earth than a simple coronary stenosis. Christiaan Vrints

Andreotti said “much discussion” went into the recommendations around coronary revascularization, but added that in left main CAD, CABG surgery is preferred strategy, although there is an equally strong recommendation for PCI in patients with low anatomic complexity.

To TCTMD, Milojevic said the writing committee took into account the recommendations of the ESC/EACTS task force, but they didn’t simply “copy and paste” them into the new CCS guidelines. Rather, the writing committee shifted the focus from left main CAD revascularization based solely on SYNTAX score towards recommendations that take into account the ability to perform complete revascularization, he said.

“We have also reemphasized the role of the heart team and, of course, informed decision making when deciding on the best treatment for a particular patient,” said Milojevic.

Beyond Coronary Stenosis

A key aspect of the new document is its acknowledgement of coronary microvascular dysfunction, which alongside epicardial coronary artery stenosis can lead to the development of myocardial ischemia and patient symptoms, Vrints said.

“In chronic coronary syndromes, paraphrasing Hamlet, there is more between heaven and earth than a simple coronary stenosis,” said Vrints.

The stepwise approach to diagnose chronic coronary syndromes is similar to recommendations from previous guidelines, said Vrints. One of the new additions is a recommendation that physicians estimate the pretest likelihood of obstructive CAD using the risk factor-weighted clinical likelihood model (class I, LOE B).

For those with a low or moderate pretest probability of obstructive disease, coronary CT angiography is recommended to diagnose obstructive CAD and to estimate the risk of MACE (class I, LOE A). For those with a moderate or high clinical likelihood of obstructive CAD, functional imaging is also recommended to confirm the diagnosis (class I, LOE B). In the event no obstructive disease is found, the guidelines advise clinicians to consider angina/ischemia in the absence of nonobstructive coronary arteries (ANOCA/INOCA).

Treatment of Patients With Multivessel CAD

The European guidelines also break from the current US recommendations for patients with multivessel disease, another area of recent disagreement between surgeons and cardiologists.

In the 2021 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) guideline for coronary revascularization, CABG surgery was downgraded in patients with three-vessel CAD from a class I to class IIa recommendation in those with mild-to-moderate left ventricular dysfunction and to class IIb in patients with normal left ventricular function. The US guidelines for chronic coronary disease, which were published 2 years later, adopted the same recommendations. The decision to downgrade surgery stemmed largely from data gleaned from ISCHEMIA.

The American Association for Thoracic Surgery (AATS) and Society of Thoracic Surgery (STS) did not endorse the ACC/AHA/SCAI revascularization guidelines and elected not to participate in drafting the recommendations for chronic coronary disease, as reported by TCTMD.  

In the 2024 ESC guidelines, myocardial revascularization remains a class I recommendation (LOE A) to improve survival and reduce long-term cardiovascular mortality and risk of spontaneous MI for CCS patients with LVEF > 35% and functionally significant three-vessel CAD. In surgically eligible CCS patients with multivessel CAD and LVEF ≤ 35%, CABG surgery is also a class I recommendation (LOE B) to improve long-term survival over guideline-directed medical therapy (GDMT) alone. 

The interpretation of evidence is not straightforward and can sometimes be extremely challenging. Milan Milojevic

Speaking during the ESC session, Andreotti said the task force placed a lot of weight on a recent meta-analysis by Eliano Navarese, MD (University of Sassari, Italy), showing that coronary revascularization plus GDMT reduced the risk of cardiac mortality compared with medical therapy alone in patients with stable CAD. The cardiac survival advantage improved with longer follow-up and was linked with a reduction in spontaneous MIs, she said.

Those findings were also confirmed in ISCHEMIA-EXTEND, said Andreotti, noting that there was a 22% lower risk of cardiovascular mortality with the invasive strategy over 7 years of follow-up.

To TCTMD, Milojevic said the writing committee embraced all the evidence, including the older studies that demonstrated a survival advantage with CABG, and it wasn’t difficult to maintain surgery as a class I recommendation in those with multivessel CAD. “The main difference between the US and European guidelines is that the US guidelines relied more on the ISCHEMIA results,” he said. “On the other side, we tried to take into account all the available evidence we have in the field.” 

Other Recommendations

With respect to GDMT for angina, the CCS guidelines provide a range of recommendations, including the use of various combinations. Short-acting nitrates are recommended for the immediate relief of angina while an initial treatment with beta -and/or calcium-channel blockers to control heart rate and symptoms is recommended for most patients (class I, LOE B).

“The guidelines do not specify first- or second-line treatment, but do provide an order on the strength of recommendation, with beta-blockers, calcium-channel blockers, and nitrates still holding the strongest class of recommendation,” said Andreotti.

In terms of antithrombotic treatment following PCI, Andreotti, noted that there will always be a balance between bleeding and thrombotic risks. Six months of DAPT is the new default strategy for most patients. In those not at high ischemic or bleeding risk, 1 to 3 months of DAPT is an option (class IIb, LOE B), just as it is for those at high bleeding risk, albeit with a much stronger recommendation (class I, LOE A). For patients at high ischemic risk, different drug combinations are endorsed by the guidelines.   

“We’ve actually allowed, with a level of evidence C, the combination of aspirin and a strong P2Y12 inhibitor in certain high-thrombotic-risk conditions, like left main disease, bifurcations, chronic total occlusions, and genetic prothrombotic genotypes,” said Andreotti. For long-term antiplatelet therapy, the guidelines also open the door to using clopidogrel instead of aspirin.    

In PCI-treated patients with an indication oral anticoagulation, the guidelines recommend stopping aspirin early followed by combination therapy with an oral anticoagulant and clopidogrel depending on baseline ischemic risk (class I, LOE A).

Finally, there are recommendations to use a high-intensity statin to reach LDL-cholesterol goals in all CCS patients (class I, LOE A), while a new addition is low-dose colchicine, which can be considered (class IIa, LOE A) to reduce residual risk associated with inflammation. Use of SGLT2 inhibitors is also recommended in patients with type 2 diabetes and CCS regardless of baseline HbA1c levels (class I, LOE A), while semaglutide, a GLP-1 receptor agonist, can be considered in patients who are overweight or obese (class IIa, LOE B). 

In general, Andreotti said the guidelines emphasize patient-centered treatment, stating that physicians should be aware that treatment of any element on the CCS continuum impacts other elements and can have an impact on outcomes and quality of life.

Milojevic praised the ESC writing committee, particularly Vrints and Andreotti, for their role in steering the guidelines process.

“They have a more difficult task to facilitate these endless discussions because we don't, obviously, see the evidence with the same eye. The interpretation of evidence is not straightforward and can sometimes be extremely challenging,” he commented.