Unstable angina

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

suspected or confirmed unstable angina

1st line – aspirin

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1st line –

aspirin

Give all patients with suspected unstable angina a single loading dose of aspirin as soon as possible, unless they have significant bleeding risk or hypersensitivity to aspirin.[1][71][73]

In practice, assess the patient’s risk of bleeding using the HAS-BLED score.[2] [ HAS-BLED Bleeding Risk Score Opens in new window ] Ensure the patient has intravenous access and discuss them with a senior colleague if they have significant bleeding risk or are actively bleeding.
Check your local protocol or discuss the patient with a senior colleague if they have hypersensitivity to aspirin.
- In practice, monotherapy with a P2Y ₁₂ inhibitor may be used in these patients (see below).[2]

Primary options

aspirin: 300 mg orally (chewed or dispersed in water) as a loading dose, followed by 75-100 mg once daily thereafter

Consider – glyceryl trinitrate

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Consider –

glyceryl trinitrate

Additional treatment recommended for SOME patients in selected patient group

Offer pain relief as soon as possible.[73]

Give up to 3 doses of translingual/sublingual glyceryl trinitrate before considering a glyceryl trinitrate intravenous infusion.[2]
Monitor blood pressure carefully when giving glyceryl trinitrate because it can cause hypotension.[1][2]

Practical tip

Do not give intravenous glyceryl trinitrate if there is:[1]

Hypotension
Marked bradycardia or tachycardia
Known severe aortic stenosis
Right ventricular infarction
Use of a phosphodiesterase-5 inhibitor (e.g., avanafil, sildenafil, tadalafil, vardenafil) for erectile dysfunction within the last 48 hours.

Primary options

glyceryl trinitrate translingual: 400-800 micrograms administered under the tongue via aerosol spray as a single dose, may repeat every 5 minutes if required, maximum 3 doses; 300-600 micrograms sublingually as a single dose, may repeat every 5 minutes if required, maximum 3 doses

Secondary options

glyceryl trinitrate: 10 micrograms/minute intravenous infusion initially, adjust dose according to response, maximum 400 micrograms/minute

Consider – morphine

Consider – anti-emetic

Plus – P2Y12 inhibitor

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Plus –

P2Y12 inhibitor

Treatment recommended for ALL patients in selected patient group

The UK National Institute for Health and Care Excellence and European Society of Cardiology (ESC) guidelines recommend dual antiplatelet therapy with aspirin plus a P2Y ₁₂ inhibitor (unless there are contraindications or excessive risk of bleeding, as assessed using the HAS-BLED score).[1][71] [ HAS-BLED Bleeding Risk Score Opens in new window ]

The ESC recommends against routine pretreatment with a P2Y ₁₂ inhibitor if the coronary anatomy is unknown and invasive coronary angiography is planned within 24 hours.[1]

Practical tip

In our expert’s opinion, dual antiplatelet therapy should only be considered after seeking specialist input from the cardiology team. Different centres in the UK have different protocols, with some recommending that P2Y ₁₂ inhibitors should be limited to patients undergoing invasive coronary angiography. Such patients should receive an individualised plan written by the interventional cardiology team. This should specify what antiplatelet therapy is advised and the recommended duration of treatment, based on current evidence, individual patient factors, and the specific interventions undertaken for each patient. Check your local guidelines and consult cardiology.

Primary options

prasugrel: <75 years of age and body weight <60 kg: 60 mg orally as a loading dose, followed by 5 mg once daily thereafter; <75 years of age and body weight ≥60 kg: 60 mg orally as a loading dose, followed by 10 mg once daily thereafter; ≥75 years of age: 60 mg orally as a loading dose, followed by 5 mg once daily thereafter

ticagrelor: 180 mg orally as a loading dose, followed by 90 mg twice daily thereafter

clopidogrel: 300 mg orally as a loading dose, followed by 75 mg once daily thereafter

Consider – anticoagulation

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Consider –

anticoagulation

Additional treatment recommended for SOME patients in selected patient group

The UK National Institute for Health and Care Excellence recommends giving fondaparinux as initial drug therapy for unstable angina unless the patient has a high bleeding risk or is undergoing immediate coronary angiography.[71] However, in our expert’s opinion fondaparinux should be given to a patient with unstable angina if immediate percutaneous coronary intervention (PCI) is possible only after seeking advice from cardiology; in centres where facility for immediate PCI is not available, or in patients presenting out-of-hours where there may be delay to PCI, fondaparinux should be given, provided there are no contraindications.

Unfractionated heparin may be considered (with dose adjustment guided by monitoring of clotting function) as an alternative to fondaparinux in patients with significant renal impairment (creatinine >265 micromoles/L [>3 mg/dL]).[71]

In practice, always assess the patient’s bleeding risk using the HAS-BLED score before giving an anticoagulant. [ HAS-BLED Bleeding Risk Score Opens in new window ] Carefully consider the choice and dose of anticoagulant for patients with a high risk of bleeding associated with:[71]

Advancing age
Known bleeding complications
Renal impairment
Low body weight.

Primary options

fondaparinux: 2.5 mg subcutaneously once daily for up to 8 days (or hospital discharge if sooner)

Secondary options

heparin: 75 units/kg (or 5000 units) intravenously as a loading dose, followed by 18 units/kg/hour intravenous infusion; adjust dose according to aPTT

Consider – referral for invasive coronary angiography ± revascularisation

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Consider –

referral for invasive coronary angiography ± revascularisation

Additional treatment recommended for SOME patients in selected patient group

Discuss the patient with the cardiology team to determine further management once the results of troponin testing are known (no dynamic rise above the 99th percentile in unstable angina) and you have performed a risk assessment. See Risk assessment under Management recommendations.

Patients with unstable angina have a significantly lower risk of death compared with patients with non-ST-elevation myocardial infarction (NSTEMI) and get less benefit from an aggressive pharmacological and invasive approach.[1][88]

Further acute management depends on the patient’s clinical presentation and a risk assessment to weigh up the risk/benefit of:

An invasive strategy with invasive coronary angiography ± revascularisation (anticoagulation will be given by a cardiologist when the patient is in the catheterisation laboratory)
- This should be performed as soon as possible for patients with very high-risk features (haemodynamic instability, recurrent or ongoing refractory chest pain, acute heart failure, life-threatening arrhythmias or cardiac arrest after presentation, recurrent ischaemic ECG changes, mechanical complications)
- This should be performed within 24 hours for patients with high-risk features (troponin-based evidence of NSTEMI, dynamic ST-segment or T-wave changes, transient ST elevation, GRACE score >140)
- This can be performed on a more selective basis for patients without any of the above high-risk features, and for patients with significant contraindications to coronary angiography.

Plus – manage hyperglycaemia

ONGOING

post-stabilisation

1st line – start (or increase current) anti-anginal medication

Plus – glyceryl trinitrate

Plus – continue dual antiplatelet therapy

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Plus –

continue dual antiplatelet therapy

Treatment recommended for ALL patients in selected patient group

Continue aspirin indefinitely unless the patient has hypersensitivity. Continue the P2Y ₁₂ inhibitor for up to 12 months.[1][71] Check your local protocol when deciding which P2Y ₁₂ inhibitor to use.

Check your local protocol or discuss the patient with a senior colleague if the patient has hypersensitivity to aspirin. In practice, monotherapy with a P2Y ₁₂ inhibitor may be used in these patients; the UK National Institute for Health and Care Excellence recommends clopidogrel.[71]
The European Society of Cardiology recommends 12 months of dual antiplatelet therapy as the default strategy, although alternate regimens can be considered in certain circumstances depending on bleeding and ischaemic risks:[1]
- Single antiplatelet therapy (preferably with a P2Y ₁₂ receptor inhibitor) for patients who are event-free after 3-6 months of dual antiplatelet therapy and who are not high ischaemic risk
- Aspirin or P2Y ₁₂ receptor inhibitor monotherapy after 1 month of dual antiplatelet therapy in patients with high bleeding risk.

Practical tip

In our expert’s opinion, dual antiplatelet therapy should only be considered after seeking specialist input from the cardiology team. Different centres in the UK have different protocols, with some recommending that P2Y ₁₂ inhibitors should be limited to patients undergoing invasive coronary angiography. Such patients should receive an individualised plan written by the interventional cardiology team. This should specify what antiplatelet therapy is advised for long-term management, based on current evidence, individual patient factors, and the specific interventions undertaken for each patient. Check your local guidelines and consult cardiology.

Primary options

aspirin: 75-100 mg once daily thereafter

-- AND --

prasugrel: <75 years of age and body weight <60 kg: 5 mg orally once daily; <75 years of age and body weight ≥60 kg: 10 mg orally once daily; ≥75 years of age: 5 mg orally once daily

ticagrelor: 90 mg orally twice daily

clopidogrel: 75 mg orally once daily

Consider – ACE inhibitor or angiotensin-II receptor antagonist

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Consider –

ACE inhibitor or angiotensin-II receptor antagonist

Additional treatment recommended for SOME patients in selected patient group

Consider an ACE inhibitor if the patient has heart failure with reduced left ventricular ejection fraction, diabetes, or chronic kidney disease.[1]

Offer an angiotensin-II receptor antagonist as an alternative if the patient is intolerant to an ACE inhibitor.[1]
Measure renal function, serum electrolytes, and blood pressure before starting an ACE inhibitor or angiotensin-II receptor antagonist.[71] In practice, if the patient has abnormal renal function or blood pressure, start with a low dose and titrate this carefully with close monitoring.

Primary options

enalapril: 2.5 mg orally once daily initially, increase gradually according to response, usual dose 10-20 mg twice daily, maximum 40 mg/day

ramipril: 2.5 mg orally twice daily for 3 days, increase gradually according to response, maximum 10 mg/day

lisinopril: 2.5 to 5 mg orally once daily initially, increase gradually according to response, maximum 10 mg/day

Secondary options

valsartan: 20 mg orally twice daily initially, increase gradually according to response, maximum 320 mg/day

losartan: 12.5 mg orally once daily initially, increase gradually according to response, maximum 150 mg/day

candesartan: 4 mg orally once daily initially, increase gradually according to response, maximum 32 mg/day

Consider – statin

Consider – ezetimibe

Consider – proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

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Consider –

proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Additional treatment recommended for SOME patients in selected patient group

A PCSK9 inhibitor monoclonal antibody may be added to statin and ezetimibe therapy if LDL-cholesterol targets are not achieved despite maximal statin and ezetimibe therapy.[1][64][108][109][110] Treatment can be started during ACS admission or at outpatient follow-up 4-6 weeks later.

Primary options

evolocumab: 140 mg subcutaneously every 2 weeks; or 420 mg subcutaneously once monthly

alirocumab: 75-150 mg subcutaneously every 2 weeks; or 300 mg subcutaneously every 4 weeks

Consider – aldosterone antagonist

Consider – sodium-glucose cotransporter-2 (SGLT2) inhibitor

Plus – discuss cardiovascular disease risk factor modification

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Unstable angina

Treatment algorithm

suspected or confirmed unstable angina

aspirin

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

glyceryl trinitrate

Practical tip

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

morphine

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

anti-emetic

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

P2Y12 inhibitor

Practical tip

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

anticoagulation

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

referral for invasive coronary angiography ± revascularisation

manage hyperglycaemia

post-stabilisation

start (or increase current) anti-anginal medication

Primary options

glyceryl trinitrate

Primary options

continue dual antiplatelet therapy

Practical tip

Primary options

ACE inhibitor or angiotensin-II receptor antagonist

Primary options

Secondary options

statin

Primary options

ezetimibe

Primary options

proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor

Primary options

aldosterone antagonist

Primary options

sodium-glucose cotransporter-2 (SGLT2) inhibitor

Primary options

discuss cardiovascular disease risk factor modification