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to promptly diagnose and manage extracoronary complications, such as the onset of HF, arrhythmias, and valvular dysfunction. Additionally, during long-term follow-up, antianginal and disease-modifying medication should be optimized and adjusted based on the development of comorbidities. The potential benefits vs. bleeding risks of antithrombotic drugs should be considered and evaluated over time. Although assessing the anginal status is traditionally considered the cornerstone of clinical follow-up, it is worth noting that angina resolves in 40% of CCS patients at 1 year with further annual decreases, most often without revascularization or adaptation of antianginal therapy.404 In contrast to patients with resolving symptoms, those with persistent or recurrent angina are at higher risk of cardiovascular death or MI.404 The worse prognosis of persisting angina, however, was only observed in patients with a previous MI.408

6.3.1 Risk factors for recurrent coronary artery

disease events Patients with established ASCVD are at high risk of recurrent events and different risk factors have been identified. The REACH registry demonstrated that, in addition to the traditional risk factors, the burden of disease, lack of treatment, and geographical location are all related to an increased risk of cardiovascular morbidity and mortality in CCS patients and validated a risk score that allows estimation of the risk for MACE.1167 Using data from stabilized CCS patients from 27 European countries included in the EUROASPIRE IV and V surveys, a new risk model with an online risk calculator to predict recurrent CVD events in patients under the age of 75 years was developed and externally validated in the SWEDEHEART registry.1168,1169 This model indicated that the risk of recurrent MACE is mainly driven by comorbidities including diabetes, renal insufficiency, and dyslipidaemia, but also symptoms of depression and anxiety. A study of patients with established CAD from the UK Biobank confirmed the value of classical risk factors, lifestyle, and sociodemographic factors in predicting recurrent MACE.1170 In addition, it was found that high genetic predisposition to CAD, low HDL-C, and younger age at first ACS event most strongly predicted the recurrence risk. A polygenic risk score, when added to the Framingham score, improved predictions of events in a large population in the USA.1171 Although the prediction of recurrent MACE has been refined, it must be emphasized that the predictive power of the different risk factors is weak and that a significant part of recurrent MACE in CCS patients remains unexplained. Furthermore, the models do not incorporate information on LV function, HF, concomitant valvular disease, atherosclerotic disease burden in other vascular beds, or the severity of existing CAD.1172 While risk factors for recurrent cardiac events have been established, no clinical studies have tested predefined clinical pathways for long-term follow-up of various types of CCS patients. As a result, the long-term clinical follow-up of CCS patients is primarily empirical, based on good clinical judgement, and on the same criteria used in the initial diagnostic process to define high risk of adverse events (Section 3.3.5 and Figure 18).

6.3.2 Organization of long-term follow-up

When scheduling long-term follow-up for CCS patients with recurring or worsening angina, it is important to consider factors such as patient type, the presence of risk factors, availability of diagnostic techniques, and cost-effectiveness following regional or national healthcare policies. Different CCS phenotypes may develop or recur during long-term follow-up, altering the follow-up needed over time. The intervals and examination methods during long-term follow-up may vary based on the CCS phenotype, coronary atherosclerotic burden, presence of CMD, and severity of ischaemic LV dysfunction.

A stepwise approach based on risk assessment can be followed, like that applied for diagnosing and treating individuals with suspected CCS. Step 1: This involves an annual clinical evaluation, by a general practitioner or a cardiologist, encompassing symptom evaluation, medication review, physical examination, a resting 12-lead ECG, and blood tests for lipid profile, renal function, glycaemic status, and full blood count. The ECG should be scrutinized for heart rate, rhythm, evidence of silent ischaemia/infarction, and evaluation of PR, QRS, and QT intervals. Any new symptoms suggestive of ACS, especially with ECG changes, warrant adherence to the 2023 ESC Guidelines for the management of patients with acute coronary syndromes. 65 Current medical therapy and lifestyle measures for risk-factor control can be maintained or optimized for asymptomatic patients. Step 2: If CCS patients develop new or worsening angina or HF symptoms, arrhythmias or ECG changes, further cardiac evaluation is crucial, especially if symptoms persist despite optimized GDMT. Recurrent CAD event risk should be assessed based on symptoms, progression of risk factors, and resting ECG changes. Echocardiography may be performed to assess LV function, cardiac dimensions, and valvular abnormalities. Exercise ECG testing may be considered to confirm symptoms and evaluate functional capacity if it alters patient management. However, routine functional testing is not recommended for asymptomatic post-PCI patients, as it has not been shown to improve outcomes compared with standard care after 2 years.1173 Step 3: CCS patients with persistent symptoms at low exercise levels despite optimized GDMT or unexpectedly reduced LV function, especially with regional contraction abnormalities, need further cardiac testing to detect the progression of CAD and assess the event risk. For patients with known non-obstructive CAD, CCTA can help detect new obstructive stenoses, evaluate atherosclerotic disease progression, and identify high-risk plaque features, while functional imaging is reasonable for detecting myocardial ischaemia and guiding further management. In patients with ANOCA/INOCA and stratified medical therapy, CCTA can be useful to detect new or progressing CAD. For patients with obstructive CAD or previous cardiac events, noninvasive functional imaging is the preferred method to detect and quantify myocardial ischaemia and/or scar. However, in patients with severely limiting angina and known severe ischaemia on functional testing or high-risk CAD on CCTA, direct referral to ICA for revascularization is preferred due to the very high risk of recurrent CAD events. Although CCTA can detect CABG graft patency and exclude in-stent restenosis (ISR) in broad lumen arteries, functional imaging is preferred for assessing patients with prior revascularization because of the high frequency of extensive CAD in these patients.1174–1176 Step 4: In all patients with recurrent or worsening anginal symptoms, lifestyle modifications, risk-factor management, and GDMT should be intensified before considering further interventions. For patients with significant inducible myocardial ischaemia or high-risk CAD, and persistent anginal symptoms despite lifestyle modifications and intensified GDMT, repeat coronary revascularization may be necessary to alleviate symptoms and improve prognosis. For patients with prior CABG experiencing stable symptoms, it’s important to optimize GDMT whenever possible. If frequent angina persists despite GDMT optimization, ICA or CCTA can assist in guiding treatment decisions.1177–1179 When symptoms are uncertain, functional testing may help clarify the presence and extent of myocardial ischaemia.

ESC Guidelines                                                                                                                                                                                          3493

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