Unstable angina and NSTEMI

• Acute coronary syndrome (ACS) is sudden, reduced blood flow to heart muscle; it spans unstable angina (symptoms without heart-cell death) through non-ST-elevation myocardial infarction (NSTEMI, symptoms plus heart-cell death) to ST-elevation myocardial infarction (STEMI).
• Most NSTEMI/UA begins when an atherosclerotic plaque ruptures or erodes and a platelet-rich thrombus blocks the artery, or when demand outstrips supply.
• The diagnosis rests on the clinical picture plus ECG changes and, for NSTEMI, a rise and fall in high-sensitivity troponin (hs-cTn) above the 99th percentile.
• Risk is stratified (GRACE, TIMI); high-risk patients (GRACE above 140) benefit from an invasive strategy, usually within 24 hours, very-high-risk patients within 2 hours.
• Treatment is aspirin plus a P2Y12 inhibitor (ticagrelor or prasugrel preferred), anticoagulation, a high-intensity statin, and secondary prevention; duration of dual antiplatelet therapy is 12 months by default.

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

1. Define acute coronary syndrome and distinguish unstable angina, NSTEMI, STEMI, type 1 and type 2 myocardial infarction.
2. Explain how plaque rupture or erosion leads to unstable angina or NSTEMI.
3. Read an ECG and a high-sensitivity troponin result in suspected NSTEMI, including the 0/1 h and 0/2 h pathways.
4. Recognise atypical presentations and the causes of chest pain with a raised troponin.
5. Apply the GRACE and TIMI risk scores to decide on an invasive strategy and its timing.
6. Choose among antiplatelet and anticoagulant regimens, with doses, and outline post-ACS care and low-resource adaptations.

Atherosclerotic acute coronary syndrome (ACS) is a group of presentations caused by suddenly reduced blood supply to the heart muscle, most often from a ruptured or eroded atherosclerotic plaque with superimposed thrombus. It includes unstable angina, NSTEMI and STEMI.^[11]

Unstable angina is ACS with symptoms of myocardial ischaemia and/or ischaemic ECG changes but no detectable heart-cell death: high-sensitivity cardiac troponin (hs-cTn, the protein released when cardiac cells are injured) is not raised above its pre-specified limit. NSTEMI is ACS with the same symptoms and ischaemic ECG changes plus a rise and fall of cardiac troponin above the 99th percentile upper reference limit, indicating myocardial infarction. STEMI is ACS with ST-segment elevation (or equivalent) on the ECG, usually from complete, persistent occlusion. These three form a clinical continuum rather than separate diseases.^[1][2]

The fourth universal definition of myocardial infarction (2018) defines infarction as a rise and/or fall of cardiac troponin above the 99th percentile upper reference limit, with evidence of myocardial ischaemia (symptoms, ECG changes, imaging abnormality, or angiographic thrombus).^[3][11] It classifies myocardial infarction into types:

• Type 1: spontaneous coronary plaque rupture or erosion with thrombus (the usual NSTEMI/STEMI mechanism).
• Type 2: oxygen supply/demand mismatch without acute plaque rupture (for example severe tachyarrhythmia, hypotension, anaemia, shock, coronary embolism).
• Type 3: sudden cardiac death before biomarkers are available.
• Type 4a/4b/4c: percutaneous coronary intervention (PCI, balloon/stent procedure)-related, stent thrombosis, or restenosis.
• Type 5: coronary artery bypass grafting (CABG, heart surgery)-related.

A second concept, myocardial injury, is an elevated troponin without ischaemia. It becomes acute myocardial injury if the troponin changes on serial testing, and chronic if it is stable; neither is a myocardial infarction.^[3]

In the United States more than a million people are admitted each year with myocardial infarction, and over 60% of those admissions are NSTEMI.^[11] In Europe the overall incidence of acute coronary syndrome is estimated at about 215 cases per 100,000 people per year, with NSTEMI stable or increasing as STEMI declines.^[11] Patients with NSTEMI are typically older, have more comorbidity, and have more extensive coronary disease than those with STEMI. Significant regional differences exist in availability of invasive cardiology, and outcomes are best where PCI (percutaneous coronary intervention, a catheter procedure to open blocked arteries) centres are accessible.

The immediate triggers are atherosclerotic. A vulnerable plaque ruptures or erodes; platelets aggregate, a thrombus (clot) forms, and the artery becomes partially or transiently obstructed. Critically, a substantial minority of NSTEMI patients have an acutely occluded artery that happens to present without ST elevation, which is why early risk assessment matters.^[11]

Underlying risk factors are the familiar cardiovascular ones: age, male sex, hypertension, diabetes, dyslipidaemia, smoking, family history, chronic kidney disease, prior coronary disease. Supply/demand mismatch (type 2 MI) can occur with severe anaemia, tachyarrhythmia, hypotension, sepsis or significant valvular disease in a narrowed artery, even without new plaque rupture.

Healthy coronary endothelium (the lining of the blood vessel) is smooth and non-sticky. In atherosclerosis, lipid-rich plaques build up in the wall. In unstable angina or NSTEMI a plaque with a thin fibrous cap ruptures or its surface erodes, exposing thrombogenic (clot-promoting) material. Platelets adhere and a thrombus grows; the artery is not always fully blocked, or blockage is intermittent, so the ECG shows ischaemia without persistent ST elevation.

Three ideas make the clinical picture understandable:

1. Partial or transient obstruction. Because flow is reduced but not zero, ischaemia is often subendocardial (the inner layer) and pain builds or recurs rather than coming as a single crushing event. Symptoms may fluctuate with autonomic tone and platelet activity.
2. Supply and demand. Tachycardia, high blood pressure or anaemia raises demand or lowers supply; a modest plaque becomes ischaemic. This is why the same mechanism produces "secondary" myocardial injury.
3. Thrombus evolves. An early platelet-rich clot can wax and wane; later fibrin (the structural protein of a clot) joins, and the artery may progress to total occlusion and STEMI. Treatment therefore aims to stop clot growth and restore perfusion before total occlusion.

Patients often describe pressure, heaviness, tightness or squeezing retrosternally (behind the breastbone), perhaps radiating to the arm, jaw, neck or back, lasting more than 20 minutes or recurring at rest, or increasing compared with prior stable angina. Associated features include breathlessness, sweating, nausea and dizziness. Unstable angina is specifically crescendo (more frequent, longer, less effort), rest or new-onset angina within the past month.

Atypical presentations are common and must be actively sought: elderly patients may present with breathlessness alone, syncope, confusion or weakness; women more often have dyspnoea, nausea, fatigue or back pain; people with diabetes may have silent ischaemia or simply breathlessness. Any new or changing chest discomfort in a person with coronary risk factors deserves an ECG.

Examination is often normal. Listen for a fourth heart sound (S4), signs of left ventricular dysfunction or the complications of infarction. Hypotension or pulmonary oedema suggests a large infarct or a mechanical complication and is an emergency.

Troponin rises in many conditions; the challenge is to decide whether the elevation is type 1 myocardial infarction (treat with antiplatelet/anticoagulant therapy and early invasive management), type 2 (treat the precipitant), or myocardial injury (treat the cause, reassess).

Up to half of troponin elevations above the 99th percentile are attributable to conditions other than type 1 myocardial infarction; clinical context and the delta (change) on serial testing matter more than any single value.^[3]

Record a 12-lead ECG within minutes of presentation and repeat it serially. In NSTEMI/UA it may show ST-segment depression, transient ST elevation, T-wave inversion or flattening, or be normal. A normal ECG does not exclude infarction. Dynamic changes (new ST depression or deepening T inversion during pain) support ischaemia. Compare with prior tracings. See ECG interpretation.

• High-sensitivity cardiac troponin is the marker of choice. Report age- and sex-specific 99th percentile upper reference limits where the laboratory provides them.
• Draw blood at presentation and again at 1 hour or 2 hours (see the pathways below).
• If the clinical picture is clear and the assay is not available, manage on the ECG and presentation and transfer to a centre with testing.
• Other markers (creatine kinase-MB, myoglobin) add little when hs-cTn is available.

Imaging helps, not diagnoses: transthoracic echocardiography (an ultrasound of the heart through the chest wall) detects new regional wall motion abnormalities and complications; chest radiograph assesses for pulmonary oedema. Assess blood count, kidney function, electrolytes and glucose. Oxygen saturation guides oxygen therapy. See cardiac physical examination.

Modern management avoids admission for every raised troponin by using accelerated diagnostic pathways. The European Society of Cardiology (ESC) recommends 0/1 h or 0/2 h algorithms. Both serialise hs-cTn; both are assay-specific, so apply the table validated for your own laboratory's assay.^[2][4]

Assay-specific example, hs-cTnT (Roche-type): rule-out at presentation if 0 h below 6 ng/L, or 0 h below 12 ng/L with a 1-hour change below 3 ng/L; rule-in if 0 h at least 52 ng/L, or a 1-hour change of at least 5 ng/L; everything else is an observation zone needing further assessment.^[4]

0/2 h algorithm: used where 1-hour logistics are difficult. For example, with a Siemens-style hs-cTnI assay the very-low group (below 3 ng/L) supports immediate rule-out, a very high group (at least 120 ng/L) supports rule-in, and intermediate values are rechecked at 2 h.^[2]

Practical points common to both:

• Troponin interpretation always needs ECG and clinical context. A rule-in threshold above the 99th percentile alone does not reliably distinguish type 1 infarction from injury; clinical judgement is stronger than any fixed number.^[3]
• Serial sampling is timed from presentation, not from the patient-noticed symptom, wherever possible.
• A very low initial hs-cTn (under 3 ng/L in many protocols) supports safe early discharge only in patients with a low probability, no dynamic ECG change and no high-risk features.
• Repeated troponin testing without a diagnostic question wastes resources and prolongs admission; follow the algorithm once only.
• Sex-specific upper reference limits improve classification, especially in women.^[3]

Diagnostic (fourth universal definition): myocardial infarction is diagnosed when there is a rise and/or fall of hs-cTn above the 99th percentile plus evidence of ischaemia. For unstable angina, troponin does not rise, but the presentation is dynamic.^[3][11]

Risk scores guide the timing of invasive management and intensity of therapy.

A score combining age, heart rate, blood pressure, creatinine, history of cardiac arrest or elevation of markers, ST deviation, and Killip class. A GRACE score above 140 identifies high-risk patients who benefit from an invasive strategy, typically within 24 hours.^[1][11] Both the ESC 2023 and ACC/AHA 2025 guidelines endorse GRACE for this purpose. Lower scores allow a delayed or selective invasive approach. GRACE does not capture operator or institutional factors, so apply clinical judgement alongside it.

A simple 0-7 scale that uses variables available at presentation:

Scores of 0-2 generally indicate low risk, 3-4 intermediate risk, and 5-7 high risk of death, myocardial infarction or urgent revascularisation within about 14 days.^[11] GRACE discriminates mortality more accurately, but TIMI is faster to calculate at the bedside.

The History, ECG, Age, Risk factors and Troponin score is primarily a chest-pain triage tool in emergency medicine. It complements cardiac risk stratification: a low score helps identify patients who may be discharged, while higher scores prompt closer monitoring or expedited inpatient testing.^[5][11]

Give aspirin without delay (chewed if the patient is not already on it; loading dose per local formulary), continuous ECG and blood pressure monitoring, oxygen only if hypoxaemic (saturation below local thresholds), and nitrates for pain or hypertension. Use morphine for persistent pain with caution: opioids delay oral P2Y12 absorption.^[6][7][8]

Add a P2Y12 inhibitor and anticoagulation, start a high-intensity statin, and arrange invasive management according to risk.

In both ESC 2023 and ACC/AHA 2025 recommendations, ticagrelor or prasugrel is preferred to clopidogrel in patients with ACS undergoing PCI.^[1][5] The ESC 2023 guideline additionally states that prasugrel should be considered in preference to ticagrelor for patients with ACS who proceed to PCI.^[1] Guidelines differ; both potent options are reasonable in practice.^[1][5]

Antiplatelet loading before the coronary anatomy is known (pretreatment) is not recommended in NSTE-ACS by the ESC (class III, level A).^[1]

• Nitrates (e.g., glyceryl trinitrate) sublingually or intravenously for ischaemic pain or hypertension, with blood pressure monitoring.
• Beta-blockers (e.g., metoprolol) early if no contraindication (heart failure, bradycardia, hypotension, shock, bronchospasm), to reduce oxygen demand and recurrent ischaemia.
• Calcium channel blockers as an alternative for rate control or vasospastic component, or when beta-blockers are contraindicated.
• Morphine for refractory pain, with awareness of antiplatelet absorption delay. Avoid NSAIDs, which increase bleeding and thrombotic risk.

Decide using ECG, troponin, GRACE score and comorbidity, following local cardiac service pathways.

The ESC 2023 and AHA 2025 guidelines define "very high" and "high" risk slightly differently, but both place shock, refractory ischaemia, heart failure from ischaemia and dangerous arrhythmias in the immediate category. A GRACE score above 140 remains the shared high-risk threshold.^[1][5][11]

Complete revascularisation (all significant coronary lesions, not just the culprit) is recommended in both STEMI and NSTE-ACS and can be performed in the index procedure or staged.^[5]

• High-intensity statin for all ACS patients; concurrent or early addition of ezetimibe if LDL cholesterol remains high (AHA: at least 70 mg/dL despite maximal statin).
• Nitroglycerin patch/tablet regimen continued according to blood pressure.
• ACE inhibitor or ARB started in hospital when there is left ventricular systolic dysfunction, diabetes, anterior infarct or hypertension; beta-blocker as above.
• Proton pump inhibitor when a patient is at high gastrointestinal bleeding risk on dual antiplatelet therapy.
• Oral anticoagulant with P2Y12 (not aspirin beyond a short window) when atrial fibrillation or another indication coexists: 1 week of triple therapy, then up to 12 months of dual therapy, shorter still in very high bleeding risk.^[1]

See atrial fibrillation and flutter and heart failure.

• Dual antiplatelet therapy for 12 months is the default in patients without high bleeding risk; shorter strategies (3-6 months, or as early as 1 month in patients at high bleeding risk) are supported by ESC.^[1][5]
• Aspirin monotherapy is continued long term unless bleeding or other factors dictate; P2Y12 monotherapy after completed DAPT is acceptable when bleeding dominates.
• High-intensity statin (and further lipid-lowering as needed) with a fasting lipid profile 4-8 weeks after initiation or dose change.
• Cardiac rehabilitation (in-person or home-based) is recommended for all patients after discharge.
• Blood pressure, diabetes and smoking management; consider colchicine/secondary prevention per local guidance.
• Bleeding precautions: avoid NSAIDs, treat anaemia, and reassess P2Y12 strategy in the frail and elderly. Avoid routine triple therapy beyond a week.

• Heart failure and cardiogenic shock from large infarct or mechanical complication.
• Arrhythmia: ventricular tachycardia or fibrillation early after infarction, atrial fibrillation, high-grade AV block.
• Mechanical complications: papillary muscle rupture with acute mitral regurgitation, ventricular septal rupture, free-wall rupture causing tamponade (days after infarct).
• Reinfarction or stent thrombosis during follow-up.
• Bleeding (gastrointestinal, intracranial, access site) from antithrombotic therapy; monitor blood count and stool occult blood.
• Post-infarction pericarditis / Dressler syndrome weeks after infarction.

See ventricular arrhythmias, bradyarrhythmias and AV block, supraventricular tachycardias, approach to tachyarrhythmias and cardiac tamponade.

Prognosis depends on infarct size, left ventricular function and comorbidity. In-hospital mortality for NSTEMI is lower than STEMI but long-term mortality remains substantial, with an excess in older and diabetic patients. Complete revascularisation and optimal medical therapy improve outcomes; risk scores remain useful at discharge and follow-up.

Prevention is secondary after the index event: antiplatelet therapy, statin, ACE inhibitor where indicated, beta-blocker, blood pressure and glucose control, smoking cessation, cardiac rehabilitation and assessment of non-culprit lesions. There is no screening test for unstable plaques; prevention targets the same modifiable risk factors.

• ECG and hs-cTn are the two tests that matter most for decision-making; prioritise 24-hour ECG access and a single validated troponin assay over exotic biomarkers.
• Aspirin is inexpensive and should be given promptly. Where clopidogrel is the only affordable P2Y12, use it; it still reduces events (CURE).
• Unfractionated heparin is inexpensive and standard; fondaparinux and enoxaparin also reduce bleeding or simplify logistics but cost and availability vary regionally.
• Invasive strategy may require transfer to a distant PCI centre; follow regional protocols for time windows and avoid prolonged delay in very high-risk patients.
• Cardiac rehabilitation can be delivered as low-cost, home-based programmes with education, exercise and risk-factor counselling.
• Avoid unnecessary troponin testing outside suspected ACS to conserve reagents; use clinical assessment and ECG first.

• ACS includes unstable angina and NSTEMI (without persistent ST elevation) and STEMI (with it).
• Type 1 MI is plaque rupture/erosion with thrombus; type 2 is supply/demand mismatch.
• Diagnosis of NSTEMI requires a rise and fall of hs-cTn above the 99th percentile plus evidence of ischaemia; unstable angina is the same syndrome without troponin elevation.
• ECG must be recorded early and may be normal; do not wait for biomarkers in high-risk presentations.
• High-sensitivity troponin pathways (0/1 h or 0/2 h) are assay-specific and safe when applied faithfully.
• GRACE above 140 selects patients for an invasive strategy, usually within 24 hours; very-high-risk features demand angiography within 2 hours.
• Ticagrelor or prasugrel is preferred to clopidogrel in ACS patients having PCI; prasugrel should be considered in preference when proceeding to PCI in ESC guidance.
• Avoid pretreatment with a P2Y12 inhibitor in NSTE-ACS.
• Anticoagulation is standard; UFH, enoxaparin or fondaparinux are used according to risk and logistics, with doses adjusted for renal function.
• Default dual antiplatelet therapy lasts 12 months; cardiac rehabilitation and secondary prevention improve outcomes.
• Up to half of troponin elevations are attributable to conditions other than type 1 MI, so interpret results in clinical context.

• ECG interpretation
• cardiac physical examination
• heart failure
• atrial fibrillation and flutter
• ventricular arrhythmias
• bradyarrhythmias and AV block
• supraventricular tachycardias
• approach to tachyarrhythmias