2.1 Acute Coronary Syndromes (STEMI & NSTEMI/Unstable Angina)

Acute Coronary Syndromes (STEMI & NSTEMI/Unstable Angina)

Acute coronary syndromes (ACS) encompass a spectrum of life-threatening myocardial ischaemic conditions resulting from sudden reductions in coronary blood flow. In the United Kingdom, coronary heart disease remains a leading cause of mortality and hospital admissions. Clinical management pivots on rapid triage, accurate electrocardiographic (ECG) interpretation, risk stratification, and timely coronary reperfusion.

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1. Pathophysiology: The Ischaemic Cascade

The fundamental pathology underlying acute coronary syndromes is the rupture, fissure, or erosion of a vulnerable atherosclerotic plaque within a coronary artery:

1. Plaque Disruption: Atherosclerotic plaques with thin fibrous caps and large lipid-rich necrotic cores are prone to mechanical shear stress. Rupture exposes subendothelial collagen, von Willebrand factor, and tissue factor to flowing blood.
2. Platelet Activation & Aggregation: Platelets adhere to exposed collagen via glycoprotein (GP) Ia/IIa and GP Ib receptors. Activated platelets degranulate, releasing adenosine diphosphate (ADP), thromboxane A2 (TXA2), and serotonin, which recruit and activate circulating platelets. Conformational activation of platelet GP IIb/IIIa receptors binds fibrinogen, creating platelet cross-links (the "white clot").
3. Thrombus Propagation: The coagulation cascade is concurrently triggered by tissue factor, generating thrombin, which converts fibrinogen into an insoluble fibrin mesh, entrapping red blood cells (the "red clot").
4. Occlusion & Myocardial Necrosis:
   • STEMI: Complete, persistent transmural coronary arterial occlusion occurs, precipitating epicardial-to-endocardial myocardial cell death within minutes to hours unless rapidly recanalised.
   • NSTEMI / Unstable Angina: Incomplete, transient, or micro-embolising occlusion causes non-transmural (subendocardial) ischaemia. When myocyte necrosis occurs, cardiac biomarkers (high-sensitivity troponin) are released into circulation (NSTEMI); when ischaemia occurs without myocyte necrosis, cardiac biomarkers remain normal (Unstable Angina).

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2. Clinical Presentation & Initial Evaluation

Classical Presentation

Patients typically report acute-onset, retrosternal chest pain or tightness, classically described as heavy, crushing, band-like, or squeezing (the "Levine sign"). The pain typically:

• Persists longer than 20 minutes at rest.
• Radiates predictably to the left shoulder, left arm, neck, jaw, or epigastrium.
• Is unresponsive or only transiently responsive to sublingual glyceryl trinitrate (GTN).
• Is accompanied by autonomic hyperactivity: diaphoresis (cold sweats), nausea, vomiting, tachypnoea, lightheadedness, and an overwhelming feeling of impending doom (angor animi).

Atypical Presentations & "Silent" Ischaemia

Clinicians must maintain a low threshold of suspicion for atypical presentations, particularly in:

• Elderly patients (≥75 years): Delirium, acute confusion, falls, or isolated profound fatigue.
• Diabetic patients: Autonomic denervation may mute visceral nociceptive transmission, presenting with "silent MI" or isolated painless dyspnoea.
• Women: More frequently present with epigastric discomfort, nausea, back pain, or breathlessness rather than classic crushing retrosternal pain.

Initial 10-Minute Assessment

Every patient with suspected ACS must undergo the following within 10 minutes of arrival in the emergency setting:

• 12-lead ECG: The single most critical initial investigation. If normal or non-diagnostic but clinical suspicion remains elevated, serial 12-lead ECGs must be recorded at 15–30 minute intervals, or continuous ST-segment monitoring initiated.
• Focused Clinical Assessment: Airway, Breathing, Circulation, Disability, Exposure (ABCDE). Assess haemodynamic stability (blood pressure in both arms to evaluate for aortic dissection, heart rate, heart sounds, JVP, lung auscultation for pulmonary crackles).
• Venous Access & Blood Sampling: Baseline full blood count (FBC), urea and electrolytes (U&Es), liver function tests, random glucose, lipid profile, and high-sensitivity cardiac troponin (hs-cTn) at presentation.

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3. Electrocardiographic Localization of Infarction

Diagnostic criteria for STEMI on a standard 12-lead ECG include persistent ST-segment elevation measured at the J-point in at least two contiguous leads:

• Chest leads (V2–V3): ≥2.5 mm in men <40 years; ≥2.0 mm in men ≥40 years; ≥1.5 mm in women (regardless of age).
• Other contiguous leads: ≥1.0 mm ST-segment elevation in limb or other precordial leads.
• New-onset Left Bundle Branch Block (LBBB): In the presence of concordant ischaemic symptoms, new or presumed new LBBB is managed as an acute STEMI equivalent.

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4. Emergency Management of STEMI: The Reperfusion Clock

Time is myocardium. Reperfusion therapy must be initiated without waiting for cardiac troponin test results.

Acute Pharmacological Stabilization

• Aspirin: 300 mg loading dose, chewed immediately for rapid buccal absorption, unless already administered by ambulance crews.
• Second Antiplatelet (P2Y12 Inhibitor): Ticagrelor 180 mg loading dose (or Prasugrel 60 mg if undergoing primary PCI; Clopidogrel 600 mg if oral anticoagulation is co-prescribed or high bleeding risk exists).
• Analgesia & Antiemetic: Intravenous Diamorphine 2.5–5 mg or Morphine 5–10 mg titrated to pain relief, co-administered with Metoclopramide 10 mg IV or Ondansetron 4 mg IV.
• Sublingual Nitrates: Glyceryl trinitrate (GTN) spray (400 mcg sublingually, repeated after 5 minutes) to alleviate coronary vasospasm and reduce ventricular preload. Contraindications: Systolic BP <90 mmHg, severe bradycardia or tachycardia, suspected RV infarction, or phosphodiesterase-5 inhibitor use (sildenafil within 24 hours, tadalafil within 48 hours).
• Oxygen Therapy: Routine high-flow oxygen is not recommended. Hyperoxia causes paradoxical coronary vasoconstriction and increases free radical injury. Administer oxygen only if pulse oximetry SpO2 <94% (or target 88–92% in patients with hypercapnic respiratory failure/COPD).

Reperfusion Strategy: Primary PCI vs. Fibrinolysis

The choice of reperfusion modality depends strictly on door-to-balloon and transit times:

1. Primary Percutaneous Coronary Intervention (pPCI):
   • The undisputed gold-standard reperfusion modality.
   • Indicated if the patient presents within 12 hours of symptom onset AND pPCI can be delivered within 120 minutes of the time of STEMI diagnosis.
   • During the procedure, unfractionated heparin (UFH) with or without glycoprotein IIb/IIIa inhibitors (e.g. tirofiban) is administered under interventional cardiology guidance.
2. Intravenous Fibrinolysis (Thrombolysis):
   • Indicated if primary PCI cannot be achieved within 120 minutes of STEMI diagnosis, provided symptom onset is within the past 12 hours and no absolute contraindications exist.
   • Door-to-needle time must be <30 minutes. Preferred agent: weight-adjusted intravenous bolus tenecteplase (or alteplase) alongside parenteral anticoagulation (enoxaparin or UFH) and dual antiplatelet therapy.
   • Absolute Contraindications to Fibrinolysis: Prior intracranial haemorrhage (any time); ischaemic stroke within the preceding 6 months; known structural vascular malformation or malignant intracranial neoplasm; major gastrointestinal bleed within the past month; known bleeding diathesis; suspected aortic dissection; non-compressible vascular puncture within 24 hours.
   • Follow-up: Repeat 12-lead ECG at 60–90 minutes post-fibrinolysis. If ST-segment elevation has failed to resolve by >50%, immediate rescue PCI is mandatory.

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5. NSTEMI & Unstable Angina Management

In acute coronary syndromes without persistent ST elevation, pathophysiology centers on partial coronary occlusion. The clinical strategy revolves around rapid risk stratification.

Diagnostic Distinction

• NSTEMI: Symptoms of cardiac ischaemia accompanied by a transient, dynamic rise and/or fall of cardiac biomarkers (high-sensitivity troponin I or T above the 99th percentile upper reference limit) with at least one value exceeding the threshold, with or without ECG changes (ST depression, T-wave inversion, or flat T waves).
• Unstable Angina: Characterised by crescendo angina, angina at rest (>20 minutes), or new-onset severe angina, with normal serial cardiac biomarkers and non-diagnostic or transiently abnormal ECG findings.

Acute Medical Management of NSTEMI

• Dual Antiplatelet Therapy: Aspirin 300 mg loading dose, followed by 75 mg daily; plus Ticagrelor 180 mg loading dose (or Clopidogrel 300 mg if high bleeding risk or indicated for long-term oral anticoagulation).
• Parenteral Anticoagulation: Fondaparinux 2.5 mg subcutaneous once daily is the agent of choice according to NICE guidelines, having demonstrated comparable efficacy to enoxaparin with significantly lower major bleeding rates. If coronary angiography and PCI proceed, unfractionated heparin is co-administered in the catheterisation laboratory. If creatinine clearance is <20 mL/min, dose-adjusted unfractionated heparin is preferred.
• Anti-ischaemic Therapy: Oral cardioselective beta-blocker (e.g. Bisoprolol 2.5–5 mg once daily) to reduce myocardial oxygen consumption, provided there are no contraindications (acute heart failure, bradycardia, hypotension, severe reactive bronchospasm). Sublingual GTN for breakthrough pain.

Risk Stratification: The GRACE Score

The Global Registry of Acute Coronary Events (GRACE) score calculates 6-month post-discharge all-cause mortality based on 8 core clinical variables: age, heart rate, systolic blood pressure, serum creatinine, Killip class (heart failure severity), cardiac arrest at admission, ST-segment deviation, and elevated cardiac biomarkers.

NICE NG185 (Acute coronary syndromes) uses the predicted 6-month mortality from a risk score such as GRACE:

• Intermediate or Higher Risk (predicted 6-month mortality above 3.0%): Offer coronary angiography (with follow-on PCI if indicated) within 72 hours of first admission, unless contraindicated.
• Lower Risk (predicted 6-month mortality 3.0% or less): Consider conservative management with non-invasive testing for ischaemia (e.g. stress echocardiography, myocardial perfusion scan or CT coronary angiography); angiography is considered if ischaemia is subsequently found.
• Clinically Unstable Patients: Carry out angiography as soon as possible (NICE); the European Society of Cardiology (ESC) uses an immediate (under 2 hours) strategy for haemodynamic instability, cardiogenic shock, refractory chest pain, acute heart failure or life-threatening arrhythmias.
• ESC Comparison: ESC guidance also describes an early invasive strategy (within 24 hours) for very high GRACE scores (above 140). For UK exam questions that ask what NICE recommends, the anchor is within 72 hours for intermediate-or-higher-risk NSTEMI/unstable angina.

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6. Comprehensive Secondary Prevention: The Core Six

Following stabilisation and revascularisation, all post-ACS patients must be initiated on optimal secondary prevention pharmacotherapy prior to hospital discharge. The core six pillars comprise:

1. Aspirin: 75 mg once daily, continued indefinitely.
2. Second Antiplatelet Agent (P2Y12 Inhibitor): Ticagrelor 90 mg twice daily (or Clopidogrel 75 mg once daily, or Prasugrel 10 mg once daily) continued for 12 months, unless high bleeding risk dictates earlier cessation.
3. High-Intensity Statin: Atorvastatin 80 mg once daily, irrespective of baseline lipid levels (a lower dose if there are interactions or high adverse-effect risk). NICE NG238 (2023) sets secondary-prevention lipid targets of LDL cholesterol 2.0 mmol/L or less, or non-HDL cholesterol 2.6 mmol/L or less. Baseline liver function tests (LFTs) should be checked and re-evaluated at 3 months.
4. ACE Inhibitor (or ARB): Titrated upward (e.g. Ramipril titrated to target dose of 10 mg daily; or Candesartan if ACEi-induced cough occurs), particularly critical for patients with left ventricular systolic dysfunction (LVEF ≤40%), hypertension, or diabetes.
5. Cardioselective Beta-Blocker: (e.g. Bisoprolol titrated to 10 mg daily), particularly indicated for patients with reduced ejection fraction, targeting a resting heart rate of 55–60 bpm. Continued for at least 12 months, or indefinitely if LVEF is impaired.
6. Sublingual GTN Spray: Prescribed PRN with comprehensive patient education on proper administration (take one spray seated; if unresolved after 5 minutes, take a second spray; if pain persists 5 minutes after the second spray, immediately dial 999).