Chronic Coronary Disease

Terminology

• Chronic coronary disease, also referred to as chronic coronary syndrome (CCS), is a long-term condition of impaired blood flow to the myocardium, most commonly due to atherosclerotic obstruction of the epicardial coronary arteries.
• The terms ischaemic heart disease, coronary artery disease, coronary heart disease, and coronary disease are often used interchangeably, although the underlying pathophysiology may also involve microvascular dysfunction in some patients.

Nature of the Condition

• The condition is typically progressive and chronic in nature.
• Patients without acute presentations who are managed in outpatient care are described as having CCD or CCS.
• In contrast, acute coronary syndromes (ACS)—which include myocardial infarction (MI) and unstable angina—represent sudden destabilisation of the disease and are managed urgently with distinct revascularisation strategies.

Clinical Manifestations

• The hallmark feature is exertional angina—chest discomfort occurring when myocardial oxygen demand exceeds supply, reproducible with activity and relieved by rest or nitroglycerin.
• Atypical presentations may include dyspnoea, fatigue, palpitations, or silent ischaemia, particularly in individuals with diabetes.
• Important complications include ischaemic cardiomyopathy, heart failure, arrhythmias, and sudden cardiac death.

Spectrum of Disease

Stable disease

• Patients may present with predictable angina or remain asymptomatic, with CCD detected incidentally through investigations.

Acute disease

• ACS, encompassing unstable angina and MI, arises from acute plaque destabilisation and requires emergency management pathways.

Pathophysiological complexity

• Although epicardial coronary atherosclerosis is the predominant cause, up to one-third of symptomatic patients may not have significant obstructive epicardial disease.
• In these cases, microvascular dysfunction—known as angina with no obstructive coronary artery disease (ANOCA)—is implicated.

Atherosclerotic causes

• Coronary disease is primarily caused by atherosclerosis of the epicardial coronary arteries.
• Atherosclerosis begins with endothelial injury, lipid accumulation, and inflammatory infiltration, leading to the formation of fatty streaks and fibrous plaques.
• Progressive narrowing of the arterial lumen reduces blood flow and oxygen delivery to the myocardium.
• Stable plaques with thick fibrous caps and calcification tend to cause exertional angina, whereas unstable plaques with thin caps and lipid-rich cores predispose to rupture and acute thrombosis.

Non-atherosclerotic causes

Vasospasm

• Transient occlusion of coronary arteries due to spasm, as seen in variant (Prinzmetal’s) angina.

Endothelial and microvascular dysfunction

• Impaired vasodilation and abnormal coronary microvascular blood flow can cause ischaemia in the absence of obstructive epicardial disease (ANOCA).

Spontaneous thrombosis or embolism

• Coronary occlusion may result from spontaneous clot formation within the vessel or embolisation from another source.

Coronary artery dissection

• Spontaneous or traumatic tearing of the coronary vessel wall creates intramural haematoma and obstructs flow.

Extrinsic compression

• Rare external compression of coronary arteries by surrounding structures.

Systemic vasculitis/arteritis

• Inflammatory conditions such as Kawasaki disease or Takayasu arteritis can damage coronary vessels and promote occlusion.

Radiation-induced injury

• Prior thoracic radiotherapy may cause long-term coronary endothelial damage, accelerating atherosclerosis and stenosis.

Atherosclerotic plaque development

• Atherosclerosis is characterised by the formation of lipid-rich plaques within the arterial wall.
• Plaque development is driven by an inflammatory process involving lipids, smooth muscle cell proliferation, matrix protein deposition, calcification, necrosis, and intraplaque haemorrhage.
• Lesions typically occur at sites of disturbed haemodynamics such as arterial bends, branch points, and regions of turbulent blood flow.

Models of plaque progression

Obstructive thick-walled plaques

• Large, fibrotic plaques gradually narrow the arterial lumen.
• Haemodynamically significant obstruction usually occurs when stenosis reaches 70–80%.
• These plaques commonly lead to chronic intermittent exertional symptoms, such as stable angina.

Vulnerable thin-walled plaques

• Thin-capped, lipid-rich plaques may not cause critical obstruction prior to rupture.
• Plaque disruption exposes thrombogenic material, leading to acute haematoma and thrombus formation.
• This may result in sudden coronary occlusion or distal embolisation, precipitating myocardial infarction.
• This model explains why:
  • Myocardial infarction can occur at sites without prior flow-limiting stenosis.
  • Interventions aimed at reducing angina (improving flow) differ from those preventing mortality (plaque stabilisation and thrombosis prevention).

Dynamic and heterogeneous disease process

• Coronary arteries can undergo compensatory outward remodelling, meaning plaque size does not always correlate with luminal narrowing or ischaemia.
• Plaque behaviour is not linear: lesions may progress, regress, or alternate between stability, erosion, and rupture.
• Microcalcification within thin fibrous caps increases mechanical stress, enhancing the likelihood of rupture.
• Stable plaques are typically associated with macrocalcification and a thick collagen matrix, conferring greater structural stability.

Global burden

• Coronary disease is the leading cause of morbidity and mortality worldwide, contributing to millions of deaths annually.
• In 2019, an estimated 197.2 million people were affected globally, with higher prevalence in men (113.7 million) compared with women (83.6 million).
• Although men demonstrate a higher prevalence and earlier onset, coronary disease remains the leading cause of mortality in women, with a 10-year delay in incidence compared with men.

Age and sex distribution

• Prevalence rises significantly with age. In the United States:
  • Among adults aged 40–59 years: 7.5% of men and 6.5% of women are affected.
  • Among adults aged 80 years or older: 30.6% of men and 20.6% of women are affected.
• Lifetime risk at age 40 is approximately 1 in 2 for men and 1 in 3 for women.

Trends in high-income countries

• Since the 1990s, mortality from coronary disease has declined in the United States, Canada, and much of Europe.
• This decline reflects advances in acute and chronic management, alongside reductions in traditional risk factors such as smoking, hypertension, and hyperlipidaemia.
• However, rising rates of obesity, sedentary lifestyle, and diabetes may counterbalance these improvements.

Trends in low- and middle-income countries

• In contrast, mortality from coronary disease is increasing in lower- and middle-income regions, where it has become the leading cause of premature death.
• The disparity is largely related to limited healthcare infrastructure, reduced access to preventive measures, and rapid adoption of Westernised diets and lifestyles.

Geographic and socioeconomic variation

• Prevalence varies widely both between countries and within populations.
• Genetic susceptibility plays a role, with heritability of coronary disease estimated at 40–60% based on twin studies.
• A positive family history, particularly of premature coronary disease, is a strong risk factor for ischaemic events in middle-aged adults.
• Social determinants of health—such as socioeconomic inequalities, cultural influences, neighbourhood environment, access to care, and exposure to adversity—are increasingly recognised as major contributors to disease burden.

Key diagnostic factors

Presence of risk factors

• Key contributors include hypertension, diabetes mellitus, smoking, hyperlipidaemia, obesity, physical inactivity, male sex, family history of premature coronary disease, and use of illicit drugs.

Typical angina symptoms

• Substernal pressure or squeezing lasting several minutes.
• Symptoms triggered by exertion or emotional stress.
• Relief occurs promptly with rest or glyceryl trinitrate.
• This symptom complex is strongly predictive of underlying coronary disease.

Atypical angina symptoms

• Chest discomfort meeting only two of the three criteria for typical angina.
• Less specific for coronary disease but more frequent in women, older adults, and those with diabetes.
• Some guidelines recommend categorising as cardiac, possibly cardiac, or non-cardiac chest pain rather than using the term “atypical.”

Symptoms of low-risk unstable angina

• Chest pain precipitated by exertion and lasting less than 20 minutes.
• Symptoms that are not escalating in intensity or frequency.
• Normal or unchanged ECG pattern.

Normal examination

• In patients with chronic stable angina, physical examination is often unremarkable.

Other diagnostic factors

Exacerbating conditions

• Thyroid disease, anaemia, hyperviscosity, arteriovenous fistula, and chronic lung disorders may worsen anginal symptoms by altering oxygen supply or demand.

Non-anginal chest pain

• Chest discomfort with only one or none of the features of typical angina.
• Predictive value is lower, but patient age and other risk factors should be considered.

Alternative or less common presentations

• Epigastric discomfort – often seen in women, older adults, or those with diabetes.
• Jaw or arm pain – anginal equivalents, especially in the left arm.
• Dyspnoea on exertion – may indicate ischaemia-induced ventricular dysfunction or act as an anginal equivalent.
• Nausea, vomiting, diaphoresis, or fatigue – sometimes associated with angina but may also suggest other causes such as anaemia or thyrotoxicosis.
• Signs of high-risk disease:
  • S3 gallop or bibasilar rales suggesting left ventricular dysfunction.
  • Mitral regurgitation murmur indicating papillary muscle involvement.
• Findings suggestive of alternative aetiologies or systemic atherosclerosis:
  • Aortic outflow murmur (aortic stenosis, hypertrophic cardiomyopathy).
  • Carotid bruits, diminished peripheral pulses, or abdominal aneurysm signs (systemic vascular disease).
  • Retinopathy (long-standing hypertension).
  • Xanthomas or xanthelasma (familial hypercholesterolaemia).

Risk factors

Age and sex

• Age is the strongest predictor of coronary risk.
• Men are affected more frequently and earlier; women’s risk accelerates after menopause.

Dyslipidaemia

• Elevated LDL cholesterol is a central driver of atherosclerosis.
• Non-HDL cholesterol, apolipoprotein B, and lipoprotein(a) add further prognostic value.
• Low HDL cholesterol and high triglycerides are linked to higher risk but are less clearly causal.

Hypertension

• Strong linear association with coronary disease mortality.
• Blood pressure control in randomised trials consistently reduces ischaemic events.

Smoking

• One of the most important modifiable risk factors.
• INTERHEART study showed smoking accounted for 36% of global myocardial infarction risk, with dose-related effects even at 1–5 cigarettes daily.

Diabetes

• Increases coronary risk two- to four-fold.
• Often coexists with obesity, hypertension, and dyslipidaemia.
• Coronary disease is the major cause of death in patients with type 2 diabetes.

Chronic kidney disease (CKD)

• Independent risk factor for coronary events.
• Lower glomerular filtration rate and albuminuria are strongly linked to adverse outcomes.
• Incorporated into the concept of cardiovascular–kidney–metabolic (CKM) syndrome.

Obesity and physical inactivity

• Central adiposity and increased BMI are associated with coronary disease.
• Sedentary behaviour strongly correlates with cardiovascular events, whereas regular exercise lowers risk.

Diet

• Low intake of fruits and vegetables and diets high in saturated fats contribute to coronary risk.

Psychosocial and social determinants

• Depression, stress, and limited social support predict coronary events.
• Broader social determinants—including education, neighbourhood environment, and healthcare access—further influence risk.

Inflammatory and systemic diseases

• HIV, rheumatoid arthritis, psoriasis, and other inflammatory conditions increase coronary risk.
• Cancer and certain therapies (thoracic radiotherapy, specific chemotherapies) further exacerbate risk.

Substance misuse

• Cocaine and amfetamines are important precipitants of acute coronary events.
• No consistent evidence supports a protective effect of alcohol.

Family history

• Family history of premature coronary disease is a recognised risk factor, though its impact is largely mediated by shared behaviours and common risk factors.

Pollution and toxins

• Chronic exposure to air pollution raises risk of coronary disease, events, and death.
• Toxic metals such as lead, mercury, cadmium, and arsenic are also implicated in cardiovascular morbidity.

Key diagnostic factors

Normal examination

• Patients with stable chronic angina often have no abnormal examination findings.

Abnormal findings suggesting high-risk disease

• S3 gallop – indicates ischaemia-induced left ventricular dysfunction.
• Bibasilar rales – suggest pulmonary congestion from left ventricular dysfunction.
• Mitral regurgitation murmur – may indicate papillary muscle dysfunction caused by ischaemia.

Abnormal findings suggesting alternative diagnoses

• Aortic outflow murmur – points to possible aortic stenosis or hypertrophic cardiomyopathy as non-coronary causes of chest pain.
• Carotid bruit, diminished peripheral pulses, or abdominal aneurysm signs – evidence of peripheral vascular disease, which increases the likelihood of concurrent coronary disease.
• Retinopathy – arteriovenous nicking or exaggerated light reflexes on fundoscopy are markers of chronic hypertension.
• Xanthomas or xanthelasma – stigmata of severe hypercholesterolaemia.

Other diagnostic factors

Non-specific systemic signs

• Tachycardia – may reflect thyrotoxicosis, anaemia, sympathomimetic drug use, or arrhythmia.
• Diaphoresis – can be related to angina but also raises suspicion of stimulant drug use or thyrotoxicosis.
• Hypoxia – indicates impaired oxygen delivery, potentially exacerbating ischaemia.
• Fatigue – may accompany angina but can also suggest systemic contributors such as anaemia.

Atypical or uncommon findings

• Epigastric discomfort – more frequent in women, older adults, or patients with diabetes.
• Jaw or arm pain – common alternative sites of anginal discomfort, especially in the left arm.
• Nausea and vomiting – may occur with angina or myocardial ischaemia.
• Dyspnoea on exertion – can represent an anginal equivalent, particularly in diabetes, but may also indicate pulmonary or haematological disease contributing to oxygen imbalance.

Risk factors identifiable on examination

Age and sex

• Advanced age is the strongest non-modifiable risk factor.
• Men are more commonly affected; in women, risk accelerates after menopause.

Hypertension

• Retinal changes, such as arteriovenous nicking, provide visible evidence of hypertensive end-organ damage.

Dyslipidaemia

• Presence of xanthomas or xanthelasma strongly suggests underlying severe hyperlipidaemia.

Obesity and inactivity

• Central adiposity may be evident on examination, reflecting increased metabolic and coronary risk.

Substance misuse

• Physical signs of stimulant misuse (e.g., tachycardia, diaphoresis) should prompt consideration as a precipitating factor.

Systemic vascular disease

• Carotid bruits, diminished peripheral pulses, or abdominal aneurysm signs suggest widespread atherosclerosis and increase suspicion of concurrent coronary disease.

Initial bedside and laboratory assessment

Resting ECG

• Recommended for all patients with suspected or established coronary disease.
• May be normal but can reveal ST–T abnormalities, prior Q-wave infarction, or atrial fibrillation.
• Baseline changes help guide subsequent testing such as echocardiography or stress imaging.

Blood tests

• Haemoglobin – detects anaemia, which reduces oxygen delivery and increases cardiac workload, sometimes causing angina even without coronary obstruction.
• Lipid profile – evaluates dyslipidaemia; high LDL cholesterol and low HDL cholesterol are associated with increased risk.
• Fasting glucose or HbA1c – identifies diabetes, a major comorbidity and prognostic factor.
• Thyroid function – considered if thyrotoxicosis or hypothyroidism could exacerbate ischaemic symptoms.

Non-invasive imaging

Echocardiography

• Rest echocardiography is widely recommended in patients with suspected CCD.
• Detects regional wall-motion abnormalities (evidence of prior MI), left ventricular dysfunction, or alternative structural pathology (e.g., valvular disease).
• Provides prognostic information in patients with established disease or comorbid heart failure.

Chest radiography

• Useful in excluding alternative thoracic causes of symptoms.
• Findings are often normal in chronic coronary disease.

Coronary CT angiography (CCTA)

• High sensitivity for detecting coronary stenosis and characterising plaque.
• Limitations include severe coronary calcification, contrast use, and radiation exposure.
• UK guidelines recommend CCTA as the preferred initial imaging test for stable chest pain, whereas US/European guidelines support either CCTA or functional stress imaging.
• Identifies not only obstructive stenosis (>50%) but also non-calcified “soft plaques” relevant to risk.

Stress imaging modalities

• Include SPECT, stress echocardiography, PET, and cardiac magnetic resonance (CMR).
• Evaluate inducible ischaemia and differentiate reversible vs irreversible myocardial injury.
• Add prognostic value beyond ECG by quantifying ischaemic burden.
• Choice of modality depends on patient factors (e.g., functional capacity, body habitus), clinical question, and local expertise.

Functional and stress testing

Exercise ECG (without imaging)

• Involves graded exercise with monitoring of ECG, symptoms, blood pressure, and heart rate.
• Prognostic scoring tools, such as the Duke treadmill score, assist in risk assessment.
• Now less favoured in guidelines because of limited diagnostic accuracy and confounding baseline ECG abnormalities.
• Contraindicated in patients unable to exercise adequately or with uninterpretable resting ECG.

Advanced CT techniques

• CT myocardial perfusion (CTP) evaluates stress vs rest myocardial contrast uptake.
• Fractional flow reserve derived from CT (FFRCT) estimates flow limitation using computational modelling.
• Both methods refine diagnostic accuracy of CCTA by assessing functional significance of stenoses.

Coronary artery calcium (CAC) scoring

• Provides an overall measure of calcified plaque burden.
• In symptomatic patients, CAC scores may be integrated into pre-test probability models but are not diagnostic for angina.
• Most useful for risk stratification in asymptomatic individuals to guide primary prevention decisions such as statin initiation.

Invasive assessment

Coronary angiography

• The gold standard for defining coronary anatomy and stenosis severity.
• Increasingly paired with fractional flow reserve (FFR) to determine whether lesions are functionally significant.
• Reserved for high pre-test probability cases, inconclusive non-invasive results, or when revascularisation is being considered.
• Carries risks including bleeding, arrhythmia, contrast nephropathy, radiation, and embolisation.

Tests for vasospasm and microvascular dysfunction

• Considered in patients with angina symptoms but unobstructed epicardial arteries.
• Vasospastic angina: assessed using ambulatory ECG monitoring or intracoronary acetylcholine provocation.
• Microvascular dysfunction: evaluated through coronary flow reserve, microcirculatory resistance indices, or acetylcholine testing.
• Tailored therapy guided by these findings may improve patient symptoms.

Pulmonary causes

Pneumonia with pleurisy

• Pain is typically sharp and worsens with inspiration.
• Associated features include cough, sputum, fever, and dyspnoea.
• Examination may reveal bronchial breath sounds and dullness to percussion over an affected area.
• Chest radiography often shows a pulmonary infiltrate, sometimes with effusion.

Gastrointestinal causes

Oesophagitis

• Presents with odynophagia and dysphagia; infectious forms are common in immunocompromised patients.
• Pill-induced injury and prior radiotherapy are important considerations.
• Candida: white–yellow plaques on endoscopy, “shaggy” mucosa on barium swallow.
• Herpes simplex virus: multiple small ulcers; Cytomegalovirus: larger, deep linear ulcers.
• Endoscopy helps exclude other causes when drug-induced oesophagitis is suspected.

Oesophageal spasm

• Causes intermittent retrosternal pain and dysphagia; symptoms may improve with glyceryl trinitrate, mimicking angina.
• Barium swallow may show a corkscrew pattern due to uncoordinated contractions.
• Oesophageal manometry demonstrates repetitive, non-propulsive contractions.

Gastro-oesophageal reflux disease (GORD)

• Produces epigastric or retrosternal burning pain radiating to the throat, often relieved by antacids.
• Typically managed empirically with acid suppression.
• Oesophageal pH monitoring confirms episodes of acid exposure (pH <4).

Peptic ulcer disease

• Epigastric pain radiating to the back, recurrent and sometimes relieved by food ingestion.
• Oesophagoduodenoscopy demonstrates gastric or duodenal ulceration.

Biliary colic

• Right upper quadrant pain occurs 15–30 minutes after meals, lasting several hours, often with nausea, vomiting, and bloating.
• Ultrasound or hepatobiliary scans usually reveal gallstones.

Musculoskeletal and rheumatological causes

Costochondritis

• Pain is localised to costochondral or costosternal joints, reproduced with palpation.
• Diagnosis is clinical.

Fibromyalgia

• Pain near the sternum and second intercostal space, associated with multiple tender points across the body (≥11/18).
• Patients often report fatigue, heaviness, and widespread musculoskeletal discomfort.
• Diagnosis relies on exclusion of other conditions and the presence of characteristic tender points.

Rib fracture / Sternoclavicular arthritis

• Localised pain with movement or palpation.
• Diagnosis usually clinical, sometimes aided by imaging.

Infectious and dermatological causes

Herpes zoster

• Prodromal dermatomal pain may mimic angina before rash develops.
• Characterised by vesicular lesions in a dermatomal distribution once established.

Psychiatric causes

Anxiety and panic disorders

• May present with chest pain, palpitations, autonomic hyperactivity, and a sense of impending doom.
• Diagnosis is clinical and based on history, after excluding organic pathology.

Cardiovascular conditions (important cardiac differentials)

• Acute pericarditis – pleuritic chest pain, pericardial rub, diffuse ST elevation.
• Angina pectoris – exertional chest pain relieved by rest or nitrates.
• Atherosclerosis / coronary artery vasospasm – alternative coronary mechanisms of ischaemia.
• Dilated cardiomyopathy – progressive dyspnoea, chest discomfort, signs of heart failure.
• Familial hypercholesterolaemia – premature coronary disease with xanthomas or xanthelasma.
• Hypertension / hypertensive heart disease – longstanding pressure overload leading to chest pain or ischaemia.
• Giant cell arteritis / Kawasaki disease – systemic vasculitides that can involve coronary vessels.

General approach

• Improve quality of life by reducing angina and restoring activity.
• Improve outcomes by lowering risks of myocardial infarction (MI), hospitalisation, and death.
• Use shared decision-making within a multidisciplinary team, aligning therapy with patient values, comorbidities, frailty, and bleeding risk.

Education and lifestyle modification

Patient education and adherence

• Provide an individualised plan that explains medicines, expected benefits, adverse effects, and what to do if symptoms worsen.
• Emphasise adherence to guideline-directed therapies for symptom relief and event reduction.

Cardiac rehabilitation

• Combine assessment, education, smoking cessation support, psychosocial care, and supervised exercise.
• Indicated after MI or revascularisation and reasonable for stable angina; benefits include lower mortality and rehospitalisation and better quality of life.
• Home-based options are acceptable alternatives when access to centre-based programmes is limited.

Physical activity

• Target ≥150 minutes/week of moderate-intensity aerobic activity (or ≥75 minutes/week vigorous), plus resistance training ≥2 days/week.
• Encourage lifestyle activity (e.g., walking breaks, stairs, gardening) in addition to structured exercise.
• Consider pre-exercise evaluation in high-risk or sedentary patients; selective stress testing may be used before vigorous activity.

Diet

• Recommend a Mediterranean-style pattern rich in vegetables, fruits, legumes, nuts, whole grains, and fish.
• Replace saturated fats with unsaturated fats; increase fibre; minimise refined carbohydrates, processed meats, sweetened drinks, and sodium; avoid trans fats.
• Limit alcohol intake; routine use of supplements (including omega-3) is not supported for event reduction.

Weight management

• Measure BMI (and consider waist circumference); counsel on dietary change and activity to achieve weight reduction in overweight/obesity.
• Consider pharmacotherapy or bariatric surgery in selected patients; acknowledge BMI limitations and focus on improving cardiorespiratory fitness and metabolic risk.

Smoking cessation

• Advise complete cessation and avoidance of second-hand smoke; offer behavioural support and pharmacotherapy.
• Stopping smoking reduces coronary mortality by roughly one third, with benefits emerging within years and approaching never-smoker risk after 10–15 years.

Stress and depression recognition and management

• Screen for depression and anxiety, particularly post-MI, given associations with poorer adherence and outcomes; treat according to need and patient preference.

Vaccination

• Recommend annual influenza vaccination to reduce adverse cardiovascular events; consider other vaccines (e.g., pneumococcal, COVID-19, RSV) based on age/comorbidity, acknowledging limited direct cardiac-outcome data.

Guideline-directed management to improve outcomes

Antiplatelet therapy (secondary prevention)

• Low-dose aspirin indefinitely for most patients with CCD; lowers non-fatal MI risk with less bleeding than higher doses.
• Clopidogrel is an alternative when aspirin is contraindicated.
• Dual antiplatelet therapy (DAPT) after ACS for ~12 months (medical, PCI, or CABG pathways); tailor duration to bleeding/ischaemic risk.
• Outside ACS, long-term DAPT is not routine; consider only in selected very high ischaemic/low bleeding risk profiles per regional guidance.
• Use bleeding-risk tools (e.g., PRECISE-DAPT, DAPT score) to guide duration; prefer gastroprotection with a PPI when on DAPT, noting no proven loss of clopidogrel efficacy with PPI co-therapy.
• In selected high-risk, non-anticoagulated patients, low-dose rivaroxaban plus aspirin lowers composite cardiovascular outcomes at the expense of more bleeding.

Lipid management

• High-intensity statin for virtually all patients with CCD unless contraindicated.
• Expect proportional risk reduction with greater LDL-C lowering (~25% fewer major coronary events per ~1.0 mmol/L [~40 mg/dL] LDL-C decrease); benefits extend to older adults with vascular disease.
• Aim for ≥50% LDL-C reduction from baseline and consider absolute targets (<1.8 mmol/L [70 mg/dL], or lower for very high risk).
• If targets unmet or statin-intolerant: add ezetimibe; in very high risk with persistent elevation, consider PCSK9 inhibitors.
• Newer non-statins (e.g., bempedoic acid, inclisiran) may be options when goals are not achieved, with outcome data evolving; routine omega-3, niacin, or fibrates are not recommended for event reduction (exception: selected use of icosapent ethyl after LDL optimisation per regional guidance).

Beta-blocker therapy

• Indicated for systolic dysfunction (HFrEF) to reduce events (e.g., metoprolol succinate, carvedilol, bisoprolol).
• Post-MI benefits are greatest early; long-term routine use in patients with preserved EF and no recent MI is not clearly beneficial and is not recommended solely to improve outcomes.
• Continue for angina control, arrhythmia, or hypertension when indicated.

Renin–angiotensin–aldosterone system (RAAS) blockade

• ACE inhibitors (or ARBs if intolerant) for CCD with hypertension, diabetes, CKD, LV dysfunction, or other vascular disease; reduce major cardiovascular events beyond BP lowering in selected high-risk groups.

Blood pressure control

• Lifestyle measures for elevated BP (120–129/<80 mmHg); initiate/adjust pharmacotherapy for hypertension (≥130/80 mmHg), generally targeting <130/80 mmHg (some older adults may target 130–140 systolic).
• Beta-blockers and ACEi/ARBs are preferred in many CCD patients; calcium-channel blockers are effective for angina relief.

Diabetes management

• In type 2 diabetes with CCD, prioritise agents with proven cardiovascular benefit independent of HbA1c: SGLT2 inhibitors (e.g., empagliflozin, canagliflozin, dapagliflozin) or GLP-1 receptor agonists (e.g., liraglutide, semaglutide, dulaglutide).
• Combination SGLT2 + GLP-1 may be used for glycaemia/weight, though additive cardiovascular benefit is not established; no role for these agents to improve cardiac outcomes in non-diabetic patients without heart failure.
• Continue metformin when tolerated; intensify lifestyle therapy and manage BP, lipids, and weight.

Anti-anginal pharmacotherapy to reduce symptoms

Short-acting nitrates

• Sublingual glyceryl trinitrate for rapid relief and pre-emptive prophylaxis before exertion; lack of relief should prompt urgent evaluation for ACS.

First-line maintenance options

• Beta-blockers, calcium-channel blockers, and long-acting nitrates reduce angina frequency; select based on heart rate/BP, comorbidities, and tolerance.
• Avoid combining beta-blockers with non-dihydropyridine calcium-channel blockers (verapamil/diltiazem) due to bradycardia/AV block risk.
• Ensure a daily nitrate-free interval to prevent tolerance; avoid PDE-5 inhibitors with nitrates.

Second-line / adjunct options

• Ranolazine, nicorandil, ivabradine, trimetazidine may be considered when first-line agents are not tolerated/insufficient; follow regional cautions (e.g., MHRA advisories for nicorandil ulceration and ivabradine bradycardia/AF; limited evidence for trimetazidine and exclusion from some UK pathways).
• Vasospastic angina: greater benefit from calcium-channel blockers and nitrates due to anti-spasm effects.

Coronary revascularisation

Indications and strategy

• Consider revascularisation to relieve refractory symptoms despite optimal medical therapy (OMT) or in carefully selected patients for prognostic benefit.
• Use physiology (e.g., FFR) and ischaemia burden to guide lesion selection; complex cases benefit from Heart Team discussion (interventional cardiology + cardiothoracic surgery).

Symptom relief

• CABG and PCI improve angina vs medical therapy in symptomatic patients
• The only blinded, placebo-controlled PCI trial showed no superiority of PCI over sham for short-term symptom/exercise improvement under intensive OMT, highlighting expectancy/placebo effects in symptom trials.

Survival and MI outcomes in stable disease

• Large trials in stable CAD (e.g., COURAGE; ISCHEMIA) did not show reductions in CV death or MI with routine revascularisation added to OMT, excluding left main disease.
• CABG confers survival benefit in selected anatomical/functional subgroups in older studies; evolving surgical techniques and contemporary medical therapy temper generalisability.
• FFR-guided PCI may improve non-fatal outcomes in selected patients; survival benefit remains unproven outside specific anatomies (e.g., left main managed surgically).

Considerations for common comorbidities

Chronic kidney disease (CKD)

• Use ACEi/ARB for event reduction when appropriate; adjust doses and choices for renally cleared drugs; minimise contrast load around PCI and involve nephrology when needed.

Heart failure (HF)

• Treat HFrEF/HFpEF per current guidelines; in ischaemic HF with LVEF ≤35% and suitable anatomy, CABG plus GDMT may improve symptoms, hospitalisations, and long-term mortality.

Atrial fibrillation (AF)

• Prefer oral anticoagulation monotherapy (often a DOAC) for stroke prevention in stable CCD; add a single antiplatelet for limited durations in selected post-PCI scenarios.
• Triple therapy (DOAC + DAPT) carries high bleeding risk and, if required post-PCI, should be as brief as possible (e.g., up to 1 month) before stepping down.

Peripheral artery disease (PAD)

• Address shared risk factors; consider exercise therapy and pharmacological options for claudication; recognise higher global atherosclerotic risk when planning antithrombotic and lipid strategies.

Symptom relief and quality of life

• With lifestyle modification and guideline-directed medical therapy (GDMT), many patients experience substantial symptom improvement.
• Within one year of optimised therapy, over half of patients (≈58%) may become angina-free.
• Observational evidence indicates that spontaneous resolution of angina may also occur, particularly in those with milder symptoms.

Disease progression and recurrence

• CCD is a dynamic process; despite effective management, a proportion of patients will develop recurrent or worsening angina due to advancing atherosclerosis.
• Symptoms may often be controlled with intensification of anti-anginal therapy.
• For patients with persistent symptoms or functional limitations despite GDMT, revascularisation can provide further symptomatic relief and improved exercise tolerance.

Broader vascular risk

• The risk factors responsible for coronary atherosclerosis also drive systemic vascular disease, including cerebrovascular and peripheral arterial disease.
• Interventions that address coronary risk factors—such as smoking cessation, lipid lowering, blood pressure control, and diabetes management—simultaneously reduce the risk of non-coronary atherosclerotic complications.

Myocardial infarction (MI)

• The most common and serious complication of CCD, which can develop at any stage of the illness.
• Caused by disruption of an atherosclerotic plaque, followed by thrombus formation and abrupt occlusion of the coronary artery.
• Patients often present with new or worsening chest pain, sometimes with haemodynamic instability, requiring immediate emergency assessment.
• Rigorous secondary prevention (aspirin, lipid-lowering therapy, smoking cessation, and control of blood pressure and diabetes) substantially reduces the risk of recurrence.

Sudden cardiac death

• Represents an abrupt cessation of cardiac activity, frequently without preceding symptoms.
• Mechanisms include acute ischaemia, infarction, or arrhythmias originating from scarred or electrically unstable myocardium.
• May present as sudden cardiac arrest, where outcomes are determined by the speed of defibrillation and resuscitation.
• Coronary disease remains the leading global cause of sudden cardiac death.

Ischaemic cardiomyopathy and heart failure

• Usually a long-term complication resulting from cumulative myocardial damage.
• Follows either irreversible myocyte loss after infarction or repeated ischaemic episodes producing chronic ventricular dysfunction.
• Most commonly evolves into heart failure with reduced ejection fraction (HFrEF), leading to dyspnoea, fluid overload, and exercise intolerance.
• The likelihood is moderate overall but rises with larger infarcts, recurrent events, or inadequate risk factor control.

Other systemic and vascular complications

Arrhythmias

• Atrial fibrillation, ventricular tachyarrhythmias, and conduction abnormalities are common after myocardial scarring or in advanced cardiomyopathy.

Cerebrovascular events

• Stroke can arise from shared atherosclerotic risk factors or cardioembolism in atrial fibrillation.

Peripheral arterial disease (PAD)

• Reflects generalised atherosclerosis and contributes to morbidity, often coexisting with CCD.

Persistent or recurrent angina

• Some patients continue to have limiting chest pain despite medical therapy, either due to progressive plaque burden or microvascular disease.

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