What are the European Society of Cardiology (ESC) recommendations for the diagnosis and management of chronic coronary syndromes (CCS)?

Updated: Sep 30, 2020
  • Author: David L Coven, MD, PhD; Chief Editor: Eric H Yang, MD  more...
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Acute Coronary Syndromes Clinical Practice Guidelines (ESC, 2020)

In late August 2020, the European Society of Cardiology (ESC) released their updated guidelines for the diagnosis and management of non ST-elevation (NSTE) acute coronary syndrome (ACS). [135, 136] The updates place increased reliance on high-sensitivity cardiac troponin testing (hs-cTn) for diagnosis, embrace coronary computed tomography (CT) imaging to rule out lower-risk patients, as well as highlight the need for personalized antiplatelet regimens, systems of care, and quality improvement. Key messages are below.


Chest discomfort without persistent ST-segment elevation (NSTE-ACS) is the main symptom that initiates the diagnostic and therapeutic chain. The myocardial pathology consists of cardiomyocyte necrosis, measured by troponin release, or, less often, myocardial ischemia without cell damage (unstable angina). Those with unstable angina have a much lower death risk and benefit less from an aggressive pharmacologic and invasive approach.

Troponin assays and other biomarkers

The ESC recommends Hs-cTn assays over less sensitive assays (higher diagnostic accuracy, same low cost). Note that many cardiac conditions other than myocardial infarction (MI) also result in cardiomyocyte injury and can raise cTn levels.

Biomarkers such as creatine kinase myocardial band (CK-MB) and copeptin may be clinically relevant in specific circumstances when used with non hs-cTn T or I (T/I). There is a more rapid post-MI reduction of CK-MB, and it may have an added value for detecting early reinfarction. Routine use of copeptin is recommended as an additional biomarker for the early exclusion of MI in the infrequent setting of unavailable hs-cTn assays.

Rapid “rule-in” and “rule-out” algorithms

Use of hs-cTn assays (higher sensitivity, diagnostic accuracy) can shorten the time interval to the second cTn assessment for detecting MI at presentation. Recommendations include using the 0 h/1 h algorithm (best option, blood draw at 0 h and 1 h) or the 0 h/2 h algorithm (second-best option, blood draw at 0 h and 2 h). Use of the 0 h/1 h and 0 h/2 h algorithms with clinical and electrocardiographic (ECG) findings aid in identifying appropriate candidates for early discharge and outpatient management.

Hs-cTn confounders

Four clinical variables affect hs-cTn levels besides the presence/absence of MI, as follows:

  • Age: Up to 300% differences in concentration between healthy very young versus “healthy” very old individuals
  • Renal dysfunction: Up to 300% differences in concentration between otherwise healthy patients with very high versus very low estimated glomerular filtration rate (eGFR)
  • Chest pain onset: Over 300%
  • Sex: About 40%

Ischemic and bleeding risk assessments

Initial cTn levels add prognostic information about short- and long-term mortality to clinical and ECG variables (higher hs-cTn levels raise mortality risk). Measure serum creatinine and eGFR in all patients with NSTE-ACS; they are prognostic factors and key elements of the Global Registry of Acute Coronary Events (GRACE) risk score (superior assessment to subjective physician assessment for the occurrence of death or MI). Natriuretic peptides may add incremental prognostic information and may aid in risk stratification.

Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a pragmatic approach for evaluating bleeding risk (includes the most recent trials of HBR patients previously excluded from clinical trials of dual antiplatelet therapy [DAPT] duration or intensity). The PRECISE-DAPT (PRE dicting bleeding omplications n patients undergoing tent implantation and subsEquent DAPT) score may be used to guide and inform decision making on DAPT duration with a modest predictive value for major bleeding. Their value in improving patient outcomes remains unclear.

Noninvasive imaging

After MI has been excluded, elective noninvasive/invasive imaging may still be indicated based on clinical assessment. Coronary CT angiography (CCTA) may be an option in those with a low-to-modest clinical likelihood of unstable angina as a normal scan excludes coronary artery disease (CAD): It has a high negative predictive value (NPV) to rule out ACS (by excluding CAD) and a positive outcome in patients presenting to the emergency department with a low-to-intermediate pretest probability for ACS and a normal CCTA. Upfront imaging with CCTA also reduces the need for invasive coronary angiography (ICA) in high-risk patients. Other imaging options based on risk evaluation include stress imaging by cardiac magnetic resonance imaging (CMRI), stress echocardiography, or nuclear imaging.

Risk Stratification for an Invasive Approach

The ESC recommends an early routine invasive approach within 24 hours of admission for NSTEMI (based on hs-cTn levels, GRACE risk score >140, and dynamic new/presumably new ST-segment changes) to improve major adverse cardiac events and possibly early survival. Highly unstable patients require immediate invasive angiography based on hemodynamic status, arrhythmias, acute heart failure, or persistent chest pain. For all other clinical presentations, a selective invasive approach may be performed based on noninvasive testing or clinical risk assessment.

Revascularization Strategies

The main technical aspects of percutaneous coronary intervention (PCI) in NSTE-ACS patients do not differ from the invasive assessment and revascularization strategies for other manifestations of CAD. Radial access is the recommended and preferred approach in NSTE-ACS patients undergoing invasive assessment with or without PCI. As NSTE-ACS commonly involves multivessel disease, base the determination of revascularization timing and completeness on the functional relevance of all stenoses, patient age and comorbidities, general clinical condition, and left ventricular function.

MI With Nonobstructive Coronary Arteries (MINOCA)

MINOCA comprises a heterogeneous group of underlying causes potentially involving both coronary and noncoronary pathologic conditions, with the latter including cardiac and extra-cardiac disorders. By consensus, myocarditis and Takotsubo syndrome are excluded. CMRI, a key diagnostic tool, identifies the underlying cause in over 85% of patients and the subsequent appropriate treatment.

Spontaneous Coronary Artery Dissection

Spontaneous coronary artery dissection is a nonatherosclerotic, nontraumatic, or iatrogenic separation of the coronary arterial tunics due to vasa vasorum hemorrhage or intimal tear. It comprises up to 4% of all ACS but has a higher reported incidence (22-35% of ACS) in women younger than age 60 years. Intracoronary imaging is very useful for the diagnosis and treatment strategy. Medical treatment remains to be established.

Pretreatment With P2Y12 Receptor Inhibitors

Due to a lack of established benefit, the ESC does not recommend routine pretreatment with a P2Y12 receptor inhibitor in NSTE-ACS patients with unknown coronary anatomy and a planned early invasive management. However, it may be considered in selected cases and based on the patient’s bleeding risk.

Posttreatment APT

Barring contraindications, DAPT consisting of a 12-month regimen of a potent P2Y12 receptor inhibitor plus aspirin is generally recommended, regardless of the stent type. DAPT duration can be shortened (< 12 months), extended (>12 months), or modified by switching DAPT or de-escalation, based on individual clinical judgment according to the patient’s ischemic and bleeding risks, the occurrence of adverse events, comorbidities, co-medications, and the availability of the respective drugs.

Triple Antithrombotic Therapy (TAT)

In at least 6-8% of patients undergoing PCI, long-term oral anticoagulation is indicated and should be continued. For eligible patients, non-vitamin K antagonist oral anticoagulants (NOACs) are preferred over vitamin K antagonists (VKAs). The ESC recommends dual antithrombotic therapy (DAT) with a NOAC for stroke prevention and single antiplatelet therapy (SAPT) (clopidogrel is preferred) as the default strategy up to 12 months after a short period up to 1 week of TAT (NOAC + DAPT). TAT may be prolonged up to 1 month when the ischemic risk outweighs the bleeding risk.

Chronic coronary syndromes clinical practice guidelines (ESC, 2019)

In August 2019, the European Society of Cardiology (ESC) released updated recommendations to their 2013 guidelines for the diagnosis and management of chronic coronary syndromes (CCS) (formerly stable coronary artery disease [CAD]). [105, 106]

The ESC introduced the term CCS in 2018 for what has been known as stable CAD to bring the terminology more in line with contemporary understanding of its development, progression, and management. The ESC indicates that “the clinical presentations of CAD can be categorized as either acute coronary syndrome (ACS) or CCS,” and that “CAD is a dynamic process” of atherosclerosis and altered arterial function “that can be modified by lifestyle, pharmacological therapies, and revascularization, which result in disease stabilization or regression.” CCS is also viewed as a type of out-of-hospital counterpart to ACS.

The updated guidelines define six clinical scenarios that reflect the heterogeneous nature of CCS, each defined by its own set of diagnostic and therapeutic concerns, as follows:

  • Suspected CAD with "stable" anginal symptoms, with or without dyspnea
  • Suspected CAD with new-onset heart failure symptoms or left ventricular (LV) dysfunction
  • Asymptomatic or stabilized symptomatic within 1 year of an ACS episode or following recent coronary revascularization
  • Asymptomatic or symptomatic more than 1 year after the initial diagnosis or revascularization
  • Angina and suspected vasospastic or microvascular disease
  • Asymptomatic with CAD detected at screening

The new phrase “clinical likelihood of CAD” uses various CAD risk factors as modifiers of pretest probability (PTP).

2019 Recommendations

Basic testing, diagnostics, and risk assessment

It is recommended that the initial test for diagnosing CAD in symptomatic patients in whom obstructive CAD cannot be ruled out based on clinical assessment alone be noninvasive functional imaging for myocardial ischemia or coronary computed tomography angiography (CTA). If coronary CTA reveals CAD of uncertain functional significance or is not diagnostic, functional imaging for myocardial ischemia is recommended.

The choice of the initial noninvasive diagnostic test is based on the clinical likelihood of CAD as well as other patient characteristics that influence test performance, local expertise, and the availability of tests.

Invasive angiography is recommended as an alternative test to diagnose CAD in patients with a high clinical likelihood and severe symptoms refractory to medical therapy, or typical angina at a low level of exercise and clinical evaluation that indicates high event risk. Invasive functional assessment must be available and used to evaluate stenoses before revascularization, unless the stenoses are very high grade (>90% diameter stenosis).

Consider the use of invasive coronary angiography with the availability of invasive functional evaluation to confirm the diagnosis of CAD in patients with an uncertain diagnosis on noninvasive testing.

Consider coronary CTA as an alternative to invasive angiography if another noninvasive test is equivocal or nondiagnostic. However, coronary CTA is not recommended in the setting of extensive coronary calcification, irregular heart rate, significant obesity, inability to cooperate with breath-hold commands, or any other conditions that would make good image quality unlikely.

When screening for CAD in asymptomatic patients, carotid ultrasound intima-media thickness (IMT) is not recommended for cardiovascular (CV) risk assessment.

Antithrombotic therapy

In patients with CCS and sinus rhythm, consider the addition of a second antithrombotic drug to aspirin for long-term secondary prevention in patients with a high risk  of ischemic events and without a high bleeding risk. This drug regimen may be considered in those with at least a moderately increased risk of ischemic events and without a high bleeding risk.

In patients with CCS and atrial fibrillation (AF) in whom oral anticoagulation (OAC) is initiated and who are eligible for a non-vitamin K antagonist OAC (NOAC), NOAC is preferred to a vitamin K antagonist (VKA). Long-term OAC therapy (a NOAC or VKA with time in the therapeutic range >70%):

  • Is recommended in patients with AF and a CHA 2DS 2- VASc score of at least 2 in males and at least 3 in females (CHA 2DS 2- VASc: ardiac failure, ypertension, ge ≥75 [doubled], iabetes, troke [doubled], ascular disease, ge 65-74, Sex [female])
  • Should be considered in patients with AF and a CHA 2DS 2- VASc score of 1 in males and 2 in females

In post-percutaneous coronary intervention (PCI) patients with AF or another indication for OAC:

  • In those eligible for a NOAC, NOAC (apixaban 5 mg bid, dabigatran 150 mg bid, edoxaban 60 mg od, or rivaroxaban 20 mg od) is preferred to a VKA in combination with antiplatelet therapy.
  • When rivaroxaban is used and concerns about high bleeding risk outweigh those about stent thrombosis or ischemic stroke, consider rivaroxaban 15 mg od over rivaroxaban 20 mg od for the duration of the concomitant single or dual antiplatelet therapy (DAPT).
  • When dabigatran is used and concerns about high bleeding risk outweigh those about stent thrombosis or ischemic stroke, consider dabigatran 110 mg bid over dabigatran 150 mg bid for the duration of the concomitant single or dual antiplatelet therapy.
  • After uncomplicated PCI, consider early aspirin cessation (≤1 week), and continuation of dual therapy with OAC and clopidogrel, if there is a low risk of stent thrombosis or if concerns about bleeding risk outweigh those about the risk of stent thrombosis, irrespective of the type of stent used.
  • Consider triple therapy with aspirin, clopidogrel, and an OAC for at least 1 month when the risk of stent thrombosis outweighs the bleeding risk, with the total duration (≤6 months) decided upon according to the assessment of these risks and clearly specified at hospital discharge.
  • In patients with an indication for a VKA in combination with aspirin and/or clopidogrel, carefully regulate the VKA dose intensity with a target international normalized ratio (INR) in the range of 2.0-2.5 and with time in the therapeutic range above 70%.
  • In patients with a moderate or high risk of stent thrombosis, irrespective of the type of stent used, dual therapy with an OAC and either ticagrelor or prasugrel may be considered as an alternative to triple therapy with an OAC, aspirin, and clopidogrel.

Other pharmacotherapy

Concomitant use of a proton pump inhibitor is recommended in patients receiving aspirin monotherapy, DAPT, or OAC monotherapy who are at high risk of gastrointestinal bleeding.

Lipid-lowering drugs:

  • If goals are not achieved with the maximum tolerated statin dose: Combination with ezetimibe is recommended.
  • For patients at very high risk who do not achieve their goals on a maximum tolerated dose of statin and ezetimibe: Combination with a PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor is recommended.

Consider angiotensin-converting enzyme inhibitors in CCS patients at very high risk of CV adverse events.

In patients with diabetes mellitus and CV disease (CVD):

  • The sodium-glucose co-transporter 2 inhibitors empagliflozin, canagliflozin, or dapagliflozin are recommended.
  • A glucagon-like peptide-1 receptor agonist (liraglutide or semaglutide) is recommended.

Treatment options for refractory angina

A reducer device for coronary sinus constriction may be considered to ameliorate symptoms of debilitating angina refractory to optimal medical and revascularization strategies.

For more information, please go to Primary and Secondary Prevention of Coronary Artery Disease, Acute Coronary Syndrome, and Atrial Fibrillation.

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