Non-ST-elevation myocardial infarction and unstable angina

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

NSTE-ACS is a working syndrome refined by serial ECG, high-sensitivity troponin and coronary assessment. Type 2 MI and non-ischaemic myocardial injury require different treatment despite similar biomarker elevation.

Risk assessment has two axes: ischaemic risk determines urgency and likely benefit from angiography; bleeding and comorbidity determine treatment harm. Both must be documented.

A low-risk result supports selective non-invasive testing and prevention assessment, but persistent or recurrent symptoms should prompt re-evaluation rather than premature discharge.

Key points

NSTEMI is acute myocardial injury with evidence of ischaemia but without persistent diagnostic ST elevation; unstable angina has ischaemia without biomarker evidence of necrosis.
Give aspirin 300 mg promptly unless contraindicated, then continue low-dose aspirin indefinitely in most patients.
Do not start dual antiplatelet therapy before unstable angina or NSTEMI is diagnosed.
Offer fondaparinux for unstable angina or NSTEMI when bleeding risk is not high, unless immediate angiography is planned.
Use serial high-sensitivity troponin and repeat ECG; one normal tracing or early troponin does not close the diagnosis.
Immediate angiography follows instability, not a numerical risk score.
When stable, use a validated risk tool; NICE offers angiography within 72 hours when predicted 6-month mortality is above 3% and there is no contraindication.
Do not give prasugrel before coronary anatomy is defined in NSTE-ACS; if selected, load it at PCI.
Balance DAPT potency and duration against bleeding, oral-anticoagulant indication, frailty, renal function and planned surgery.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Atherosclerotic plaque disruption

Rupture or erosion of a coronary plaque exposes thrombogenic material and produces a platelet-rich thrombus that may be subtotal, intermittent or occasionally completely occlusive. Smoking, diabetes, hypertension and dyslipidaemia increase the underlying atherosclerotic risk.

Intermittent plaque-related obstruction

A plaque-associated thrombus can wax and wane or shed distal microemboli, causing rest or crescendo ischaemia without persistent ST elevation. Fixed coronary disease may increase vulnerability, but supply-demand imbalance without acute atherothrombosis is assessed separately as type 2 myocardial infarction when it causes acute ischaemia, or as myocardial injury when ischaemic evidence is absent.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Thrombus formation
Plaque disruption activates platelets and coagulation within a coronary artery. The resulting thrombus may cause subtotal, intermittent or complete occlusion; the absence of persistent ST elevation does not reliably predict the angiographic degree of obstruction.
2
Reduced myocardial oxygen supply
Thrombotic obstruction, local vasoconstriction and distal microembolisation reduce perfusion. Oxygen delivery becomes inadequate for myocardial demand, particularly within the vulnerable subendocardial layers.
3
Reversible ischaemia develops
Ischaemic myocardium alters electrical repolarisation and contraction, producing pain, ST depression or T-wave change. The initial ECG can nevertheless remain normal or non-specific.
4
Necrosis distinguishes NSTEMI
Sufficiently prolonged ischaemia kills cardiomyocytes and causes a rise or fall in circulating troponin, defining NSTEMI when clinical evidence of acute ischaemia is also present.
5
Unstable angina remains non-necrotic
When coronary ischaemia causes new, rest or crescendo symptoms without detectable myocardial necrosis, the syndrome is unstable angina. Recurrent obstruction can still progress to infarction.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Unstable NSTE-ACSRed flag

Refractory or recurrent rest pain, shock, acute heart failure, serious arrhythmia or dynamic widespread ST change requires immediate invasive assessment.

NSTEMI

A rise or fall of troponin with at least one value above the 99th centile plus clinical, ECG, imaging or angiographic evidence of acute ischaemia.

Unstable angina

New, crescendo or rest ischaemic symptoms without myocardial necrosis; high-sensitivity assays have reduced but not abolished this diagnosis.

Dynamic ischaemic ECGRed flag

New ST depression or transient ST elevation during pain materially raises risk even if the initial troponin is low.

Bleeding hazardRed flag

Active bleeding, recent intracranial haemorrhage, severe thrombocytopenia or urgent surgical need changes antithrombotic strategy and requires senior input.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Serial 12-lead ECGFirst step
Why
Detect dynamic ischaemia and rhythm complications.
Interpretation and limitations
Repeat during pain; transient changes may be more diagnostic than the pain-free tracing.
02
Serial high-sensitivity troponin
Why
Identify acute myocardial injury under the assay-specific rule-in or rule-out pathway.
Interpretation and limitations
Require clinical evidence of ischaemia before calling acute injury NSTEMI.
03
GRACE risk estimation
Why
Estimate mortality risk and support invasive timing in stable NSTE-ACS.
Interpretation and limitations
NICE uses predicted 6-month mortality above 3% to offer angiography within 72 hours; instability overrides the score.
04
Full blood count, renal function, electrolytes, glucose and coagulation
Why
Identify anaemia, bleeding, renal dosing issues and reversible stressors.
Interpretation and limitations
Recalculate drug and contrast risk as physiology changes; do not use renal impairment alone to deny beneficial care.
05
Transthoracic echocardiography
Why
Assess LV function, regional motion and mechanical or alternative structural disease.
Interpretation and limitations
Offer after NSTEMI and consider after unstable angina; use urgently for heart failure or shock.
06
Coronary angiography
Why
Define culprit anatomy and enable PCI or surgical planning.
Interpretation and limitations
Non-obstructive findings require a structured MINOCA, spasm, microvascular, SCAD or non-ischaemic evaluation.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

ST-elevation myocardial infarction

Persistent diagnostic ST elevation or another recognised acute occlusion pattern requires an emergency reperfusion pathway. The ECG pattern does not by itself prove complete arterial occlusion, and serial ECGs are important because findings can evolve.

Type 2 myocardial infarction or non-ischaemic injury

Type 2 myocardial infarction requires acute ischaemia from a supply-demand imbalance unrelated to acute coronary atherothrombosis; a troponin rise without ischaemic evidence is myocardial injury, not infarction. Sepsis, anaemia, hypoxia or tachyarrhythmia may provide the alternative mechanism.

Myocarditis

Myocarditis may reproduce pain, ECG changes and troponin elevation. Inflammatory or electrical features and a non-coronary injury pattern on cardiac magnetic resonance favour myocarditis.

Pulmonary embolism

Pulmonary embolism can cause chest pain, breathlessness and troponin release. Pleuritic symptoms, hypoxaemia, thromboembolic risk and right-heart strain distinguish it from primary coronary ischaemia.

Acute aortic syndrome

Abrupt severe pain radiating to the back, pulse or blood-pressure asymmetry and neurological signs raise concern for dissection. Antithrombotic treatment may be harmful until this is addressed.

Additional chapter-specific clues

Type 2 MI or injury mimic

Anaemia, hypoxaemia, sepsis, tachyarrhythmia, pulmonary embolism and myocarditis can cause troponin elevation; seek ischaemic evidence and mechanism.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01Preferred routeInitial NSTE-ACS careFirst stepPreferredSuspected unstable angina or NSTEMI without persistent ST elevation

1Perform ABCDE, monitoring, ECG and serial assay-specific troponin; treat pain and hypoxaemia when present.
2Give aspirin 300 mg unless contraindicated; once unstable angina or NSTEMI is diagnosed, give fondaparinux unless bleeding risk is high or immediate angiography is planned.
3Assess instability, ischaemic risk, bleeding risk, comorbidity and any ongoing oral-anticoagulant indication.
4EscalationEscalate any recurrent pain, dynamic ECG change, arrhythmia, heart failure or haemodynamic deterioration.

02EscalationImmediate invasive strategyEscalationClinical instability or recurrent refractory ischaemia

1Contact interventional cardiology for immediate angiography without waiting for GRACE calculation.
2Use unfractionated heparin for immediate angiography or PCI; if fondaparinux was already given, NICE requires additional systemic UFH in the catheter laboratory. ESC procedural dosing is 70–100 units/kg IV without a glycoprotein IIb/IIIa inhibitor or 50–70 units/kg IV with one, adjusted to activated clotting time and bleeding risk.
3Select P2Y12 therapy with anatomy, bleeding risk, anticoagulation and PCI plan known; do not pretreat with prasugrel.
4Monitor in critical or coronary care and evaluate mechanical or shock complications.

03Preferred stable routeRisk-guided angiographyPreferredStable NSTE-ACS after initial treatment

1Calculate predicted 6-month mortality using an established risk tool and apply clinical judgement.
2Offer angiography within 72 hours when risk is above 3% and there is no contraindication.
3Use radial access when suitable and physiology for intermediate lesions; proceed to PCI or Heart Team discussion as anatomy indicates.
4If invasive treatment is not appropriate, document why and optimise medical therapy and follow-up.

04AlternativeLower-risk conservative strategyAlternativePredicted risk 3% or lower with no recurrent ischaemia

1Continue monitored reassessment until the serial ECG and troponin pathway is complete.
2Consider non-invasive ischaemia testing before discharge or soon after if angiography is not performed.
3Optimise antianginal and secondary-prevention treatment according to the final diagnosis.
4Provide explicit return advice for recurrent rest pain, breathlessness, syncope or bleeding.

Key medicines and prescribing safety6 treatments · regimens, roles and cautions

Foundation antiplatelet treatment in unstable angina and NSTEMI.

Aspirin

300 mg orally as a single loading dose as soon as possible, then usually 75 mg once daily indefinitely.

Active major bleeding or true hypersensitivity; assess gastroprotection and combined antithrombotic bleeding risk.

Anticoagulation for unstable angina or NSTEMI unless immediate angiography is planned or bleeding risk is high.

Fondaparinux

2.5 mg by subcutaneous injection once daily, started after diagnosis and continued for up to 8 days or until earlier discharge.

Contraindicated with active clinically significant bleeding, acute bacterial endocarditis or creatinine clearance below 20 ml/min. If serum creatinine is above 265 micromol/l, NICE advises considering UFH adjusted to clotting monitoring. At PCI after fondaparinux, add IV UFH: 70–100 units/kg without a glycoprotein IIb/IIIa inhibitor or 50–70 units/kg with one, adjusted to activated clotting time and bleeding risk.

P2Y12 component of DAPT for many medically managed or invasively treated NSTE-ACS patients.

Ticagrelor

180 mg orally once, then 90 mg twice daily with aspirin 75–150 mg daily, usually for 12 months unless modified.

Bleeding, previous intracranial haemorrhage, severe hepatic impairment, strong CYP3A interactions, dyspnoea and bradyarrhythmia; avoid routine combination with a necessary oral anticoagulant.

P2Y12 component of DAPT after coronary anatomy is known and PCI is proceeding.

Prasugrel

When PCI is selected: 60 mg orally at the time of PCI, then 10 mg once daily; 5 mg once daily after the load for body weight under 60 kg and, only if justified, age 75 or over.

Do not give before anatomy is defined in NSTE-ACS. Contraindicated after stroke or TIA, in active bleeding and in severe hepatic impairment; heightened bleeding risk at low weight or older age.

Alternative P2Y12 inhibitor when ticagrelor or prasugrel is unsuitable, bleeding risk is high or anticoagulation strategy favours it.

Clopidogrel

300 mg oral loading dose, or 600 mg when PCI is intended in selected patients under 75 according to protocol, then 75 mg once daily.

Active bleeding, CYP2C19 interactions and variable response; choose loading dose from timing, age, PCI and anticoagulant plan.

High-intensity secondary prevention after confirmed ACS.

Atorvastatin

80 mg orally once daily for established CVD, unless interactions, adverse-effect risk or preference require a lower dose or alternative.

Liver disease, myopathy, pregnancy and interacting medicines; monitor lipids and transaminases under NICE NG238.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Recurrent ischaemia or infarction

An unstable plaque or residual severe stenosis can thrombose again, extend myocardial necrosis or become completely occlusive. Recurrent rest pain and dynamic ECG change indicate continuing risk.

Arrhythmia and sudden deterioration

Ischaemic myocardium becomes electrically unstable and may develop bradyarrhythmia, ventricular tachycardia or fibrillation. Arrhythmia can abruptly reduce cardiac output before extensive necrosis is evident.

Left-ventricular failure

Loss of functioning myocardium and ischaemic stunning impair contraction and raise filling pressures. Acute pulmonary oedema, functional mitral regurgitation or cardiogenic shock may follow.

Long-term cardiovascular events

Coronary atherosclerosis persists beyond the acute episode. Without effective secondary prevention, patients remain at increased risk of recurrent infarction, heart failure, stroke and cardiovascular death.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Continuous rhythm and recurrent-ischaemia monitoring during the unstable phase.
Serial ECG and troponin with exact symptom and sampling times.
Daily or clinically indicated haemoglobin, platelet and renal review while receiving antithrombotic treatment.
Access-site and bleeding surveillance after angiography, including occult retroperitoneal bleeding after femoral access.
LV-function assessment and heart-failure review before discharge after NSTEMI.
Document DAPT duration, anticoagulant interaction plan, lipid therapy, rehabilitation and follow-up.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Instability outranks GRACE

Risk scores guide stable patients; refractory pain, shock, acute heart failure or malignant arrhythmia requires immediate angiography.

Fondaparinux needs PCI heparin

Fondaparinux alone does not provide adequate catheter protection during PCI; add systemic IV UFH in the catheter laboratory and adjust the procedural dose to glycoprotein IIb/IIIa use, activated clotting time and bleeding risk.

Prasugrel waits for anatomy

Loading before the angiogram in NSTE-ACS increases bleeding without a proven pre-PCI benefit.

Troponin does not identify plaque

A dynamic elevation still needs evidence of ischaemia and a mechanism before type 1 NSTEMI treatment is assumed.

Unstable angina is a clinical diagnosis

High-sensitivity troponin has made it less common, not impossible.

Oral anticoagulation changes DAPT

Avoid mechanically adding full ACS DAPT to anticoagulation; select agent and duration from ischaemic and bleeding risk.

11Common pitfallsFrequent interpretation and management errors.

01
Calling any troponin rise NSTEMI without evidence of ischaemia.
02
Waiting for GRACE calculation in a haemodynamically unstable patient.
03
Giving fondaparinux alone during PCI without procedural UFH.
04
Loading prasugrel before coronary anatomy is defined in NSTE-ACS.
05
Discharging without stating the antiplatelet and anticoagulant combination and intended stop dates.