Non ST Elevation Myocardial Infarction and Unstable Angina

Acute coronary syndrome without persistent ST elevation, comprising non ST elevation myocardial infarction where troponin is raised, and unstable angina where it is not. The distinction between the two is made retrospectively by troponin and does not alter the initial management.

Pathophysiology and the treatment implication

The occlusion is partial or intermittent and the thrombus is platelet rich rather than fibrin rich. This is the reason fibrinolysis is not only ineffective but harmful in this group: lysing a partially occlusive platelet rich thrombus exposes further thrombogenic surface and increases the rate of infarction and death. Treatment is therefore antiplatelet and anticoagulant therapy with anti ischaemic measures, followed by risk stratified invasive assessment.

Risk categories that determine timing of angiography

• Very high risk, requiring immediate angiography within 2 hours: haemodynamic instability or cardiogenic shock; recurrent or ongoing chest pain refractory to medical therapy; life threatening arrhythmia or cardiac arrest; mechanical complication; acute heart failure attributable to the syndrome; and recurrent dynamic ST or T wave changes, particularly intermittent ST elevation.
• High risk, requiring angiography within 24 hours: a confirmed rise and fall in troponin consistent with infarction; dynamic ST or T wave changes; and a GRACE score above 140.
• Intermediate risk, requiring angiography within 72 hours: diabetes, renal impairment with an estimated glomerular filtration rate below 60, an ejection fraction below 40 percent, early post infarction angina, prior percutaneous intervention or bypass surgery, and a GRACE score of 109 to 140.
• Low risk: non invasive assessment with stress testing or computed tomography coronary angiography before or shortly after discharge.

• Chest discomfort at rest, of new onset, or of increasing frequency, duration or severity, or occurring at a lower threshold than previously. Any of these patterns constitutes unstable angina.
• Anginal equivalents as described for acute coronary syndrome generally.
• Symptoms that are ongoing at presentation carry a higher risk than symptoms that have resolved.
• Autonomic features: diaphoresis, nausea and vomiting.

High risk clinical features

Ongoing pain, haemodynamic instability, pulmonary oedema, a new murmur, arrhythmia, syncope, and pain refractory to nitrates and opioids.

Examination

Frequently normal. Assess specifically for signs of heart failure, new murmurs, and for the alternative diagnoses of dissection, pulmonary embolism and pericarditis, since anticoagulating a dissection is catastrophic.

Electrocardiographic patterns defining risk

• ST depression of more than 0.5 mm, or dynamic T wave inversion of 2 mm or more, strongly suspicious for ischaemia: high risk unstable angina or non ST elevation myocardial infarction.
• Normal or non diagnostic ST segment or T wave changes: intermediate or low risk unstable angina.
• Repeat the twelve lead electrocardiogram at 30 minutes and use continuous ST segment monitoring. Dynamic change is the finding that upgrades risk, and it is only detected if the tracing is repeated.
• If ST elevation develops at any point, move to the ST elevation pathway.

Initial actions

• Establish intravenous access and send blood for urea and electrolytes and high sensitivity troponin.
• Obtain high sensitivity troponin at least 4 hours after symptom onset, not before, since an earlier sample cannot exclude infarction and a negative result taken too early gives false reassurance.
• Aspirin 300 mg to chew, with the same exclusions as before.
• Nitroglycerin sublingual spray 0.4 mg every 5 minutes to a maximum of three doses or until pain resolves, with the same contraindications: systolic pressure below 90 mmHg or 30 mmHg below baseline, heart rate above 100 or below 50 per minute, right ventricular infarction, and phosphodiesterase 5 inhibitor use within 24 hours for sildenafil and vardenafil or 48 hours for tadalafil.
• Fentanyl 25 to 50 micrograms intravenously if pain is not relieved by three doses of nitroglycerin, repeated once after 5 minutes if pain persists. Consult a cardiologist or physician for persistent pain and consider an intravenous nitroglycerin infusion.
• Consider a chest radiograph.
• Continuous cardiac monitoring.

Risk stratification with the HEART score, combining history, electrocardiogram, age, risk factors and troponin.

The decision point

If any of the following is present, consult a cardiologist or physician:

• High sensitivity troponin above the laboratory cutoff.
• HEART score above 3 points.
• ST depression.
• Dynamic electrocardiographic changes.

If none is present:

• If the troponin was taken less than 4 hours from symptom onset, repeat it at least 4 hours after onset.
• If the repeat troponin remains below the laboratory cutoff and there is no evidence of ischaemia or infarction, the patient can be discharged with or without cardiology follow up.

Discharge criteria, all of which must be met

• Two electrocardiograms which are normal, with no ST depression and no dynamic changes.
• High sensitivity troponin below the laboratory cutoff at 4 hours or more from the onset of symptoms, or at 3 hours from admission to the emergency department.

Patients meeting these criteria have a low short term risk of major adverse cardiac events. Provide clear written safety netting advice to return immediately with recurrent pain, and arrange outpatient assessment where the clinical suspicion of coronary disease remains despite the negative testing, since a negative rule out excludes acute infarction but not underlying coronary disease.

Antiplatelet therapy

• Aspirin 300 mg loading dose, then 75 to 100 mg daily indefinitely.
• A P2Y12 inhibitor, with the timing of loading determined locally and often deferred until the coronary anatomy is known, particularly where bypass surgery is a possibility:
• Ticagrelor 180 mg loading then 90 mg twice daily, which is preferred in most patients. Warn about dyspnoea, which occurs in around 15 percent and is usually transient, and about bradyarrhythmia.
• Prasugrel 60 mg loading then 10 mg daily, used at the time of intervention, contraindicated with previous stroke or transient ischaemic attack, and dose reduced to 5 mg in those aged 75 or above or weighing under 60 kg.
• Clopidogrel 300 to 600 mg loading then 75 mg daily, used where the newer agents are unavailable, in patients on oral anticoagulation, or where bleeding risk is high.
• Glycoprotein IIb/IIIa inhibitors are reserved for bail out use at the time of intervention with high thrombus burden.

Anticoagulation

• Fondaparinux 2.5 mg subcutaneously daily, which has the most favourable balance of efficacy and bleeding in medically managed patients, with additional unfractionated heparin at the time of intervention to prevent catheter thrombosis.
• Enoxaparin 1 mg/kg subcutaneously twice daily, reduced to 1 mg/kg once daily where the creatinine clearance is below 30 mL/min, and with careful dosing in the elderly.
• Unfractionated heparin as a 60 units/kg bolus to a maximum of 4000 units, then 12 units/kg/hour to a maximum of 1000 units/hour, titrated to the activated partial thromboplastin time, which is preferred in severe renal impairment and where the anticoagulant effect may need rapid reversal.
• Continue anticoagulation until intervention or for the duration of the admission in medically managed patients.

Anti ischaemic therapy

• Nitrates: sublingual for acute pain, and an intravenous infusion titrated to pain and blood pressure for ongoing ischaemia, with the same contraindications.
• Beta blockade orally within 24 hours in the absence of heart failure, hypotension, bradycardia, heart block, asthma and cocaine associated ischaemia. Bisoprolol 2.5 mg daily or metoprolol 25 mg twice daily, titrated to a resting heart rate of 50 to 60 per minute.
• A rate limiting calcium channel blocker such as diltiazem or verapamil where beta blockade is contraindicated by asthma, provided there is no left ventricular dysfunction. Dihydropyridines alone cause reflex tachycardia and should not be used without beta blockade.
• Cocaine associated chest pain is managed with benzodiazepines, nitrates and phentolamine. Beta blockade is avoided given unopposed alpha stimulation with coronary vasoconstriction.

Invasive management

• Coronary angiography with a view to percutaneous intervention or bypass surgery, timed by risk category.
• An early invasive strategy reduces recurrent ischaemia, reinfarction and rehospitalisation in intermediate and high risk patients. In genuinely low risk patients a conservative strategy with non invasive testing is appropriate and avoids procedural harm.
• Radial access is preferred, with lower bleeding and lower mortality than femoral access.
• Assess renal function and hydrate before contrast exposure in patients with renal impairment.

Additional therapy

• High intensity statin such as atorvastatin 80 mg daily, started before discharge irrespective of the baseline lipid profile.
• Angiotensin converting enzyme inhibitor in patients with left ventricular dysfunction, heart failure, hypertension, diabetes or chronic kidney disease.
• Proton pump inhibitor for gastroprotection in patients on dual antiplatelet therapy with gastrointestinal risk factors, using pantoprazole where clopidogrel is prescribed to avoid the CYP2C19 interaction.
• Echocardiography to assess left ventricular function.
• Glycaemic control, potassium and magnesium correction.

Bleeding risk

Assess it formally, since bleeding after acute coronary syndrome carries a mortality comparable to reinfarction. Consider age, renal function, anaemia, prior bleeding, weight and concurrent anticoagulation, and adjust antithrombotic intensity and duration accordingly. In patients requiring oral anticoagulation for atrial fibrillation or a mechanical valve, minimise the duration of triple therapy and use clopidogrel rather than ticagrelor or prasugrel.

Secondary prevention and follow up

Dual antiplatelet therapy for 12 months with the duration individualised by ischaemic and bleeding risk, statin, beta blocker, angiotensin converting enzyme inhibitor where indicated, cardiac rehabilitation, structured smoking cessation, dietary and exercise advice, control of blood pressure, diabetes and lipids, influenza vaccination, and screening for depression and anxiety, which are common, under treated and independently associated with worse outcomes.