Chronic coronary syndrome and stable angina

• Chronic coronary syndrome (CCS) is the current name for the long-term course of coronary artery disease: a process that ranges from silent plaque to exertional chest pain, rather than a single event.
• The 2019 European Society of Cardiology (ESC) guideline replaced the older term "stable angina" with CCS, because the same disease can obstruct epicardial vessels, disturb the microcirculation, or both.^[1]
• The pain of stable angina is a supply–demand mismatch: narrowed coronary arteries cannot increase blood flow enough for the workload, so cardiac muscle becomes ischaemic during exertion and recovers at rest.
• Management has four pillars: treat risk factors and lifestyle, relieve symptoms with anti-anginal drugs chosen by mechanism and comorbidity, prevent heart attacks with antiplatelet agents and statins, and revascularise selected high-risk patients.
• Resting tests can be normal. The diagnosis is often made from the history plus an exercise or stress test, or imaging of the coronary arteries when the pre-test probability is high.

By the end of this page you should be able to:

1. Explain why CCS replaced the term "stable angina" and what disease processes are included.
2. Relate an atherosclerotic stenosis to the three features that make exertional angina typical.
3. Stratify a patient's pre-test probability of obstructive coronary artery disease (CAD) using the 2024 ESC risk-factor-weighted model.
4. Choose and interpret the first appropriate investigation: ECG, exercise ECG, stress imaging, coronary CT, or invasive angiography.
5. Build a long-term drug regimen (anti-anginal, antiplatelet, statin, and, when indicated, ACE inhibitor) with realistic doses.
6. Apply the 2024 ESC and 2023 AHA/ACC revascularisation indications, including the SYNTAX threshold for left main disease.
7. Manage special groups (women, diabetes, INOCA/microvascular angina, older adults) and advise on driving.
8. Recognise the prognosis and the low-resource adaptations.

"Stable angina" names a symptom, not the whole disease. The 2024 ESC guideline therefore treats CCS as a spectrum, from silent plaque discovered by chance to long-standing exertional chest pain. Angina is the commonest clinical face of it. Classification follows both the anatomy (obstructive versus non-obstructive disease, single versus multivessel disease, left main involvement) and the mechanism (fixed stenosis, microvascular dysfunction, vasospasm, or a combination). Mixed pictures are common, and more than one mechanism often coexists.

Coronary artery disease remains one of the main causes of death and disability worldwide, and its chronic forms now exceed acute presentations in prevalence. Reported frequencies vary with age, sex and region, and with how the disease is diagnosed. Because the figures depend heavily on the diagnostic method used, they are not reproduced here. The clinically important point is that the disease begins years before symptoms, so risk-factor control in earlier life matters as much as treatment after the first pain.

The cause is atherosclerosis driven by endothelial injury and lipid accumulation, amplified by the classic risk factors. The 2024 ESC model lists five that it weights into the pre-test probability: cigarette smoking (including e-cigarettes), arterial hypertension, diabetes mellitus, obesity, and a family history of premature cardiovascular disease.^[1] Other contributors include dyslipidaemia, chronic kidney disease, physical inactivity, systemic inflammation, and (after menopause) female sex. Familial hypercholesterolaemia and lower-limb arterial disease also increase probability and are not captured by the weighted model.^[1] There is no single modifiable trigger; the strength of CCS programmes is that most of these risks are treatable.

The story has four layers, from plaque to pain.

Fixed stenosis and flow reserve. An atherosclerotic plaque narrows the lumen of an epicardial artery. At rest, coronary blood flow is usually adequate even through a tight stenosis, because the small vessels downstream dilate and maintain perfusion (this is coronary autoregulation). During exertion, myocardial oxygen demand rises, and a healthy artery can increase flow several-fold. A significantly stenosed artery cannot; beyond its (largely exhausted) reserve, demand outstrips supply, the subendocardium becomes ischaemic, and the patient feels pressure-like chest discomfort. Rest removes the excessive demand, flow again meets need, and the pain fades within minutes.

Endothelial dysfunction. Even before a stenosis becomes flow-limiting, damaged endothelium produces less nitric oxide and releases vasoconstrictors, so vessels fail to dilate with stress. This explains symptoms with only modest angiographic disease.

Microvascular dysfunction and vasospasm. In a growing proportion of patients, especially women, epicardial arteries are open but the small arterioles or the endothelium of larger vessels fail to dilate, or spasm. This is the angina with no obstructive coronary arteries (ANOCA/INOCA) group. It produces the same pain with different mechanisms, and it needs different tests and treatment.

Myocardial ischaemia itself. When supply falls, the myocardium switches to anaerobic metabolism, lactic acid accumulates, and metabolites stimulate cardiac sensory nerves that enter the spinal cord at C8–T4. The brain interprets this input as a pressure or heaviness, often referred to the arm, neck or jaw rather than localised to the chest. Reperfusion after ischaemia can also produce transient ST change and a brief post-exercise fall in blood pressure.

Typical (or "definite") angina has all three of these features, according to the classic clinical definition used in both the ESC and AHA traditions:^[1]

1. Constricting discomfort (pressure, tightness or heaviness, rather than a sharp or stabbing pain) in the front of the chest, neck, shoulders, arms or upper abdomen.
2. Provoked by exertion or emotional stress (an imbalance between oxygen demand and supply; the pain settles within minutes of stopping).
3. Relieved by rest or by nitrates within about five minutes.

Atypical angina has two of the three features. Non-cardiac chest pain has one or none. The ESC 2024 clinical-likelihood model also scores dyspnoea on exertion (wheeze or difficult breathing aggravated by exercise) as a high-weight anginal equivalent (2 points, against 1 point for each typical chest feature)^[1], which matters because breathlessness, not chest pain, is the presenting complaint in many women and older adults.

A useful vignette: a 62-year-old smoker with hypertension describes a crushing retrosternal pressure that comes on climbing hills, forces him to stop, and disappears within three to four minutes of rest. He now notices it when carrying heavy bags, and occasionally when walking in cold wind. Nothing hurts at night in bed. This is typical angina until proven otherwise.

There are no cardiac signs that diagnose CCS directly. Blood pressure may be raised; the apex beat is usually undisplaced. Listen for signs that change the plan:

• A murmur, ejection click or dyspnoea suggests valvular disease (aortic stenosis) or hypertrophic cardiomyopathy rather than simple angina. See cardiac physical examination.
• Signs of heart failure (elevated jugular venous pressure, basal crepitations, peripheral oedema) point to ischaemic cardiomyopathy. See heart failure.
• A bruit or absent pulses suggest peripheral arterial disease, which often coexists.
• Pallor and tachycardia suggest anaemia, which can make mild stenoses symptomatic.

Always check blood pressure in both arms and look for clues to dyslipidaemia and diabetes.

The most common error is to confuse chronic, exertional, promptly relieved pain with an acute coronary syndrome. The table separates the main mimics.

The ECG is usually normal between attacks in pure angina. Look for:

• Evidence of a prior silent myocardial infarction (Q waves).
• Left ventricular hypertrophy or strain from hypertension or aortic stenosis.
• ST–T abnormalities that could indicate ischaemia at rest or prior change.
• Arrhythmia that might explain symptoms (atrial fibrillation, bradycardia).

A normal resting ECG does not exclude CCS. See ECG interpretation.

Exercise testing is the simplest functional test. It is most useful in patients with an intermediate pre-test probability and a readable resting ECG. ST-segment depression, a fall in blood pressure, or exercise-induced chest pain are abnormal. A strongly positive test (early, widespread ST depression, arrhythmia or hypotension) predicts extensive CAD and indicates invasive angiography. Contraindications include acute coronary syndrome, severe aortic stenosis, uncontrolled arrhythmia, and a left bundle branch block or paced rhythm (which make ST changes uninterpretable).

Stress echocardiography, stress perfusion cardiovascular magnetic resonance (CMR) and myocardial perfusion scintigraphy (SPECT/PET) detect ischaemia in patients with an uninterpretable ECG or intermediate–high probability. They add functional significance to anatomical findings and allow simultaneous assessment of left ventricular function. Stress CMR and PET also permit quantification of coronary blood flow, which helps the INOCA group.

CTCA is the "gatekeeper" test for low-risk patients. A coronary artery calcium (CAC) score of 0 allows reclassification from low to "very low" risk, with a cited negative predictive value for obstructive disease of about 95%, so further functional testing is usually unnecessary.^[1] In low–moderate probability patients, CTCA directly shows luminal narrowing and plaque, and rules out significant disease with high confidence. Its weakness is overcalling artefact in heavily calcified vessels.

Invasive angiography is recommended for patients with very high probability (>85%), for those with refractory symptoms despite optimal medical therapy, and for anyone in whom revascularisation is likely.^[1] It gives the anatomy, but a stenosis seen on angiography is not necessarily flow-limiting; functional assessment is needed.

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) measure the pressure drop across a stenosis during hyperaemia or in the wave-free period of diastole, respectively. They remain the functional yardstick for deciding whether an epicardial stenosis warrants stenting or bypass (Class IA in both ESC 2024 and standard practice).^[1] Use them whenever an angiographic lesion is of uncertain haemodynamic significance.

When epicardial arteries are unobstructed but symptoms persist, a complete invasive functional study is recommended (Class I, level B).^[1] Endpoints:

• Coronary flow reserve (CFR) < 2.5 (vasodilator capacity).
• Index of microcirculatory resistance (IMR) > 25 on thermodilution, or hyperaemic microvascular resistance (hMR) > 2.5 on Doppler (microvascular resistance).
• Epicardial or microvascular spasm on acetylcholine testing (high dose 100–200 μg), or endothelium-dependent dysfunction (low dose 2–20 μg).

Non-invasive alternatives (PET/CMR myocardial blood flow, echocardiographic coronary flow velocity reserve) are increasingly used but are not yet equivalent for defining the endotype.

The 2024 ESC guideline replaces the older Diamond–Forrester estimates with a risk-factor-weighted clinical likelihood model. Prevalence of obstructive CAD has fallen in Western populations because of prevention programmes, so older models overestimated probability, especially in low-risk groups.^[1]

Symptom score (0–3 points), from the ESC 2024 figure:^[1]

• Constricting pain behind the sternum or radiating to neck/shoulder/arm: 1 point.
• Aggravated by physical or emotional stress: 1 point.
• Relieved by rest or nitrates within 5 minutes: 1 point.
• Exertional dyspnoea (wheeze or difficult breathing on exercise): 2 points.

Risk-factor points come from smoking, hypertension, diabetes, obesity and family history of premature cardiovascular disease. These modify the symptom score to place the patient in one of five bands:

Two reminders. First, the model does not include familial hypercholesterolaemia, renal failure, systemic inflammatory disease or peripheral arterial disease; these must be added by judgement.^[1] Second, the model does not stratify functional (microvascular or vasospastic) disease; clinical experience carries more weight there.

Management separates into four parallel streams: symptom relief (anti-anginal drugs), event prevention (antiplatelet agents, statins, ACE inhibitors where indicated), lifestyle and risk-factor control, and revascularisation where it changes prognosis or symptoms. In CCS these streams are complementary. The 2024 ESC guideline emphasises patient-centred care in which understanding the disease, risk-factor modification and a healthy lifestyle are as important as prescriptions.^[1]

• Mediterranean-style diet, at least 150 minutes of moderate-intensity (or 75 minutes of high-intensity) aerobic exercise weekly, plus resistance training twice weekly, where tolerated.^[2]
• Stop smoking, including e-cigarettes, and limit alcohol.^[1][2]
• Aim for a blood pressure target appropriate to the patient, optimise diabetes control (HbA1c targets per local guidance), and weight reduction.
• Target LDL cholesterol < 55 mg/dL (< 1.4 mmol/L) in high-risk patients, achieved with high-intensity statins and, if needed, ezetimibe or PCSK9 inhibitors.^[1]
• Enrol patients with a recent infarct, revascularisation, stable angina or spontaneous coronary dissection in cardiac rehabilitation.^[2]
• Do not prescribe hormone replacement therapy (oestrogen-only or combined) to protect a postmenopausal woman's heart. NICE advises against offering it for either primary or secondary prevention of cardiovascular disease; menopausal symptoms are a separate indication, and the usual risk-factor measures above remain the way to lower her risk.^[12]

The 2024 ESC guideline drops the idea of "first-line" and "second-line" anti-anginal drugs and adopts a "diamond" approach: all classes sit on the same level, and the choice follows the mechanism of ischaemia and the patient's comorbidities. Beta-blockers, non-dihydropyridine calcium channel blockers, dihydropyridine calcium channel blockers, nitrates/nicorandil, trimetazidine, ranolazine and ivabradine are the agents available.^[1] Monotherapy is started; combinations are added when symptoms persist, preferring drugs from different classes. The target for most rate-limiting agents is a resting heart rate of 55–60 beats per minute.^[3]

Why nitrates relieve the pain. Nitroglycerin releases nitric oxide in vascular smooth muscle, which relaxes it. The veins dilate most, so blood pools in the periphery, less blood returns to the heart, and the pressure that fills the left ventricle at the end of diastole (preload, the left ventricular end-diastolic pressure) falls. A smaller, less stretched ventricle has lower wall tension and uses less oxygen; a lesser dilatation of the arterioles also eases the pressure the ventricle pumps against (afterload). The label notes that dilatation of the large epicardial arteries probably matters less for relief of exertional angina than this fall in preload.^[9]

Note on ranolazine dose: the US label (500–1000 mg twice daily)^[5] and European prolonged-release labelling (375–750 mg twice daily)^[4] reflect different formulations; use the one on your local pack.

In CCS without atrial fibrillation or another indication for anticoagulation:

• Single antiplatelet therapy is standard: low-dose aspirin 75–100 mg daily (AHA/ACC 2023).^[2] If aspirin is not tolerated, clopidogrel is a reasonable alternative.^[2]
• ESC 2024 adds a Class IB recommendation for aspirin in primary prevention when there is evidence of CAD but no infarct or revascularisation, and for the first time recommends clopidogrel as a valid alternative to aspirin when aspirin is not tolerated (Class IA).^[1]
• After PCI, dual antiplatelet therapy (aspirin + clopidogrel/P2Y12 inhibitor) for at least 6 months, then single antiplatelet. In high bleeding risk and low ischaemic risk, shorten to 1–3 months, then single antiplatelet (Class IA, ESC 2024).^[1][2]
• Residual thrombotic risk: in selected patients at higher ischaemic risk without a need for oral anticoagulation or dual antiplatelet therapy, low-dose rivaroxaban 2.5 mg twice daily plus low-dose aspirin may be considered.^[2]
• Colchicine 0.5 mg daily may be considered for secondary prevention when residual inflammatory risk remains (ESC 2024 Class IIa A; AHA/ACC 2023 Class IIb).^[1][2]

• High-intensity statin to reach LDL cholesterol < 55 mg/dL (< 1.4 mmol/L) in high-risk patients; add ezetimibe and/or PCSK9 inhibitor if needed.^[1]
• The 2023 AHA/ACC pathway recommends intensifying non-statin therapy when LDL is ≥ 55 mg/dL in very-high-risk patients, or ≥ 70 mg/dL in others on maximally tolerated statin. Check LDL 4–12 weeks after titrating the dose.^[2]
• Statins are continued even when angina is controlled: they reduce events, not symptoms.

• Renin-angiotensin-aldosterone system inhibitors (ACE inhibitors or ARBs) improve symptoms, reduce hospitalisation and prolong survival in higher-risk CCS patients (hypertension, diabetes, chronic kidney disease, left ventricular dysfunction).^[2]
• Control blood pressure with a renin-angiotensin blocker, a calcium channel blocker and/or a thiazide, avoiding combinations that worsen conduction when a rate-limiting CCB is used.
• SGLT2 inhibitors and GLP-1 receptor agonists are recommended in selected CCS patients with type 2 diabetes or obesity even without diabetes.^[2]

The 2024 ESC guideline renews the prognostic indications:

• Significant left main stenosis (≥ 50%): Class IA.
• Multi-vessel disease with stenosis ≥ 70%: Class IA.
• Single- or two-vessel disease involving the proximal anterior descending artery: Class Ib.
• Extensive ischaemia (> 10% left ventricular ischaemia) with preserved ejection fraction (> 35%): revascularise for prognosis as well as symptoms.^[1]
• Favour revascularisation over medical therapy only when pharmacological therapy has failed to control symptoms (Class IA).^[1] For patients with reduced EF (< 35%), the decision should be multidisciplinary.^[1]

Type of revascularisation:

• CABG is generally preferred in diabetes mellitus, with high anatomical complexity, reduced ejection fraction and low surgical risk. In left main disease, CABG is preferred when the anatomy is complex (SYNTAX score > 22); PCI is considered equivalent when the anatomy is less complex (SYNTAX score < 22, Class IA).^[1][2]
• PCI is a valid alternative, guided by intracoronary imaging (IVUS or optical coherence tomography) in complex lesions, left main, bifurcations and long lesions.^[1]
• All decisions should be made by a Heart Team (interventional cardiologist, cardiac surgeon, imaging specialist, anaesthetist) with shared decision-making.
• Revascularisation relieves symptoms reliably; its effect on mortality depends on the anatomy and left ventricular function. Major trials (COURAGE, ISCHEMIA, BARI-2D) showed no mortality benefit from routine non-urgent revascularisation over optimal medical therapy in stable disease, so optimise drugs before procedures.^[2]

When symptoms persist despite good medical therapy and angiography shows no obstructive disease, complete invasive functional testing is recommended (Class I, level B)^[1] to define the endotype:

• Endothelium-independent microvascular dysfunction: CFR < 2.5 with IMR > 25 (thermodilution) or hMR > 2.5 (Doppler) → optimise anti-anginals (often beta-blocker/CCB + ranolazine or trimetazidine).
• High resting flow with normal resistance → treat risk factors; consider ranolazine.
• Epicardial vasospasm on acetylcholine (100–200 μg) → non-dihydropyridine CCB; nitrates may worsen spasm in some endotypes, so titrate carefully.
• Microvascular spasm on acetylcholine → CCB ± long-acting nitrate/nicorandil.

Anti-anginals that match mechanisms matter more here than in obstructive disease.

• Progression to myocardial infarction or sudden death from plaque rupture.
• Development of ischaemic (often non-transmural) myocardial infarction, sometimes silent.
• Ischaemic cardiomyopathy and heart failure with reduced ejection fraction.
• Atrial or ventricular arrhythmias, including episodes of ventricular tachycardia in severe ischaemia.
• Repeated hospitalisation for refractory angina or revascularisation.

Prognosis in CCS depends on the extent of CAD, left ventricular function, comorbidity burden and risk-factor control, far more than on the symptom label. Revascularisation of suitable high-risk anatomy reduces spontaneous infarction and cardiovascular mortality; in symptom-driven disease, the goal is a comfortable, active life. Stable angina is not benign (events continue), but with modern therapy many patients live for years with a good quality of life.

• Treat hypertension, dyslipidaemia, diabetes, obesity and smoking before symptoms appear.
• A coronary artery calcium score of zero in a low-risk patient with chest pain is reassuring and reduces the need for further imaging.^[1]
• Cardiac rehabilitation after any coronary event, procedure or new diagnosis of angina.^[2]

Women. Women are more likely to present with breathlessness, fatigue or atypical discomfort, and are more likely to have INOCA. Standard prevention (statins, antiplatelets, risk-factor control) applies. AHA 2023 and ESC 2024 both stress closing sex disparities in testing and treatment. Stress imaging and coronary function testing should be used when symptoms and risk are suggestive but CT or exercise ECG is inconclusive. See atrial fibrillation and flutter for the common comorbidity of palpitations.

Diabetes mellitus. The combination of diabetes and multivessel CAD involving the proximal LAD favours CABG with a left internal mammary artery graft.^[2] SGLT2 inhibitors or GLP-1 receptor agonists reduce events even when glycaemia is already controlled. Low blood pressure or bradycardia limits beta-blocker up-titration; ranolazine (which lowers HbA1c) and trimetazidine (metabolically neutral) are useful anti-anginals in diabetes. Monitor renal function with ranolazine.

Older adults. Apply the same four pillars, but start drugs at low doses, check renal and hepatic function, and watch for postural hypotension, bradycardia and falls. Cardiac rehabilitation remains beneficial. Reduced life expectancy from comorbidity shifts the priority towards symptom relief over long-term prognostic revascularisation.

Pregnancy. Manage jointly with cardio-obstetrics, maternal medicine and cardiology; many anti-anginal drugs do not have established safety in pregnancy. Revascularisation, when needed, requires an individualised plan.

• A resting ECG and careful history carry most of the diagnosis; use the 2024 ESC pre-test probability to avoid unnecessary imaging.
• Exercise ECG, available with a treadmill and a manual blood-pressure cuff, is a good first functional test when imaging is unavailable.
• Treat the main drivers: stop smoking, control blood pressure with a cheap generic, advise a Mediterranean-style diet using local foods, and add a generic statin and low-dose aspirin for secondary prevention.
• Where coronary CT or stress imaging is unavailable, treat by risk and symptom severity, and revascularise at a regional centre patients with left main or severe three-vessel disease.
• Colchicine 0.5 mg daily is inexpensive and may reduce events when residual inflammatory risk is present (where licensed).

In the UK, a driver with angina may continue to drive a car or motorcycle unless the angina occurs at rest, while driving, or with emotion; if it does, driving must stop until symptoms are controlled.^[11] Those with a bus, coach or lorry (group 2) licence must notify the Driver and Vehicle Licensing Agency. After PCI or a heart attack, observe the usual recovery intervals; check local regulations elsewhere. Always remind patients not to drive during an anginal attack and to pull over safely.

• CCS is the modern term for the stable, chronic course of coronary artery disease; stable angina is its commonest symptom.
• The 2019 ESC guideline renamed "stable angina" to CCS because epicardial, microvascular and functional mechanisms can coexist.
• Typical angina has three features: constricting discomfort, provoked by exertion or emotion, relieved by rest or nitrates within minutes.
• Diagnosis often proceeds from pre-test probability to CTCA in low–moderate risk and to stress imaging or invasive angiography in higher risk; a calcium score of 0 is reassuring (~95% negative predictive value).
• The 2024 ESC model weights typical symptoms and five risk factors to place patients in five probability bands.
• Anti-anginal drugs are now one "diamond": beta-blocker, dihydropyridine CCB, non-dihydropyridine CCB, nitrate/nicorandil, ranolazine, ivabradine, trimetazidine, chosen by mechanism and comorbidity, with no dogmatic first line.
• Realistic maintenance doses: bisoprolol 5–10 mg daily; amlodipine up to 10 mg; diltiazem up to 360 mg; sublingual nitroglycerin 0.3–0.6 mg; ranolazine 500–1000 mg twice daily; ivabradine 5–7.5 mg twice daily; nicorandil 5–10 mg twice daily (maximum 20 mg twice daily); trimetazidine 20 mg three times daily or 35 mg modified release twice daily.
• Antiplatelet therapy: aspirin 75–100 mg daily (or clopidogrel if not tolerated); DAPT for at least 6 months post-PCI; consider shortening with high bleeding risk.
• Statins aim for LDL < 55 mg/dL in high-risk patients; ACE inhibitors/ARBs help when risk factors or left ventricular dysfunction coexist.
• Revascularisation indications include left main ≥ 50%, multivessel ≥ 70%, proximal LAD disease, and extensive ischaemia with preserved function; CABG preferred in complex/left main and diabetes, PCI equivalent in less complex anatomy (SYNTAX < 22).
• Women and patients with INOCA often need functional coronary testing; do not stop at a normal angiogram when symptoms persist.
• Nitrates relieve angina mainly by venodilatation, which lowers preload and wall tension; hormone replacement therapy is not offered for heart protection (NICE); pneumonia with pleuritic pain is a non-cardiac mimic.
• Driving is usually allowed for cars; angina at rest or while driving means stop until controlled.

• Heart failure
• ECG interpretation
• Atrial fibrillation and flutter
• Cardiac physical examination
• Ventricular arrhythmias, bradyarrhythmias and AV block, supraventricular tachycardias, and the approach to tachyarrhythmias (MedGrasp cardiology topics) are the usual rhythm complications to rule out in chest pain.