Recommendations
Urgent
Give all patients with suspected acute coronary syndrome (ACS) a single loading dose of aspirin as soon as possible, unless they have aspirin hypersensitivity or significant risk of bleeding.[1][71]
In practice, assess the patient’s risk of bleeding using the HAS-BLED score. [ 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 high 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 P2Y12 inhibitor may be used in these patients.[2]
The UK National Institute for Health and Care Excellence recommends giving the anticoagulant 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.
Offer pain relief with glyceryl trinitrate as soon as possible. Add morphine early if glyceryl trinitrate is not effective.[73]
In practice, observe all patients in the accident and emergency department or a chest pain unit until the results of troponin testing are known (there will be no dynamic elevation in troponin above the 99th percentile in unstable angina).
In the community, refer all patients to hospital as an emergency if you suspect an ACS and they:[73]
Currently have chest pain
Are currently pain-free, but have had chest pain within the last 12 hours and a resting 12-lead ECG is abnormal or unavailable
Have had a recent ACS (confirmed or suspected) and develop further chest pain.
Key Recommendations
Risk assess the patient once the results of troponin testing are known (there will be no dynamic elevation in troponin above the 99th percentile in unstable angina) to determine further management.[71] See Investigations under Diagnosis recommendations.
Use a validated risk scoring system that predicts 6-month mortality (e.g., Global Registry of Acute Coronary Events [GRACE])[71] [ GRACE Score for Acute Coronary Syndrome Prognosis Opens in new window ]
Discuss the patient with the cardiology team to determine further management based on the results of troponin testing and risk assessment.
Patients with unstable angina have a significantly lower risk of death compared with patients with non-ST-elevation myocardial infarction and benefit less from an aggressive pharmacological and invasive approach.[1][88]
Further acute management depends on the patient’s clinical presentation and risk assessment:
Guidelines recommend dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor, unless there are contraindications or excessive risk of bleeding[1][71]
An invasive strategy with invasive coronary angiography ± revascularisation (anticoagulation will be given by a cardiologist when the patient is in the catheterisation laboratory) if patients have very high- or high-risk features, or on a selective basis without risk factors.[1][71]
Long-term management should include aspirin (plus a P2Y12 inhibitor normally given for up to 12 months as part of dual antiplatelet therapy), anticoagulation, an ACE inhibitor, a beta-blocker, a statin, and a sodium-glucose cotransporter-2 (SGLT2) inhibitor, as well as cardiac rehabilitation and modification of risk factors for cardiovascular disease (CVD).[1] See Stable ischaemic heart disease.
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 P2Y12 inhibitor (e.g., prasugrel, ticagrelor, clopidogrel) may be used in these patients.[2]
Anticoagulation
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 HAS-BLED 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.
Pain relief
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]
Add morphine early if glyceryl trinitrate is not effective. Consider giving an anti-emetic if giving morphine or if the patient develops nausea or vomiting.[95]
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 24-48 hours.
Monitoring
In practice, observe all patients in the accident and emergency department or a chest pain unit until the results of troponin testing are known (there will be no dynamic elevation in troponin above the 99th percentile in unstable angina). Monitor the following:[73]
Recurrence or increase in intensity of pain or other symptoms
Vital signs
Heart rhythm
Repeated resting 12-lead ECGs
Effectiveness of pain relief.
Practical tip
Suspect acute myocardial infarction (MI) if the patient requires oxygen because hypoxia is not a feature of unstable angina. See ST-elevation myocardial infarction and Non-ST-elevation myocardial infarction.
In the community
Refer all patients to hospital as an emergency if you suspect an acute coronary syndrome and they:[73]
Currently have chest pain
Are currently pain-free, but have had chest pain within the last 12 hours and a resting 12-lead ECG is abnormal or unavailable
Have had a recent acute coronary syndrome (confirmed or suspected) and develop further chest pain.
Risk assess the patient once the results of troponin testing are known (no dynamic rise above the 99th percentile in unstable angina) to determine further management with either an invasive approach (invasive coronary angiography ± revascularisation) or a conservative approach, to weigh up the risks and benefits of these.[71]
The UK National Institute for Health and Care Excellence recommends:[71]
A full clinical history (including age, previous MI, and previous percutaneous coronary intervention or coronary artery bypass grafting)
A physical examination (including measurement of blood pressure and heart rate)
A resting 12-lead ECG, looking particularly for dynamic or unstable patterns that indicate myocardial ischaemia
Blood tests (such as troponin I or T, creatinine, glucose, and haemoglobin)
A validated risk scoring system that predicts 6-month mortality (e.g., Global Registry of Acute Coronary Events [GRACE]). [ GRACE Score for Acute Coronary Syndrome Prognosis Opens in new window ] Use predicted 6-month mortality to categorise the patient’s risk of future adverse cardiac events as follows.[71]
Predicted 6-month mortality | Risk of future adverse cardiac events |
|---|---|
≤1.5% | Lowest |
>1.5% to 3.0% | Low |
>3.0% to 6.0% | Intermediate |
>6.0% to 9.0% | High |
>9.0% | Highest |
Evidence: Risk assessment
In people with unstable angina risk assessment tools should be used to predict their future risk of adverse cardiovascular outcomes and mortality. European and UK guidelines suggest using the GRACE risk score.
In its guidance on the early management of unstable angina and non-ST-elevation myocardial infarction (NSTEMI; last updated 2020, although evidence had not changed from 2010) the UK National Institute for Health and Care Excellence (NICE) evaluated the evidence for methods of patient risk stratification.[96]
NICE included studies where the non-ST-segment-elevation acute coronary syndrome (ACS) population was n>500 and the study population contained ≥60% people with NSTEMI or unstable angina.
NICE identified 14 observational studies assessing a total of eight risk scores. Five of these studies compared the performance of two or more different risk scores.
NICE reported discrimination (the ability to accurately distinguish high-risk from low-risk patients, measured with the c-statistic) and calibration (the ability to estimate the actual risk of an adverse outcome).
GRACE versus the Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (PURSUIT) risk score:
Two studies (Canadian ACS-1 [n=2925] and ACS-2 [n=1728] registries) in people with non-ST-segment-elevation ACS showed no difference, with both having good discrimination for mortality in hospital and at 1 year[97][98]
PURSUIT, however, had poor calibration, meaning it consistently overestimated the risks compared with GRACE.[97]
PURSUIT, GRACE, and the Predicting Risk of Death in Cardiac Disease Tool (PREDICT) all seemed to have better discrimination for mortality compared with the Thrombolysis In Myocardial Infarction (TIMI) score.
In the Canadian ACS-2 registry, PURSUIT and GRACE had significantly better discrimination than TIMI for mortality in hospital and at 1 year (in-hospital mortality: PURSUIT c-statistic = 0.80 vs. GRACE c-statistic = 0.81 vs. TIMI c-statistic = 0.68; 1-year mortality: PURSUIT c-statistic = 0.77 vs. GRACE c-statistic = 0.79 vs. TIMI c-statistic = 0.69).[98]
Based on registry data from the Mayo Clinic in the US (people with confirmed MI, n=717], PREDICT had significantly better discrimination of mortality at 28 days (PREDICT c-statistic 0.78 vs. TIMI c-statistic 0.59, P <0.001 between risk scores).[99]
In the Myocardial Infarction National Audit Project (MINAP) database (n=100,686) of people in England and Wales with acute coronary syndromes, complex scores with a greater number of components (PURSUIT and GRACE) were compared with more simple models (the Simple Risk Index [SRI] and Evaluation of Methods of Management of Acute Coronary Events [EMMACE]).[100]
All four scores showed similarly high discrimination for predicting mortality in hospital and at 30 days.
The 2023 European Society of Cardiology (ESC) guideline for the management of acute coronary syndromes recommends that risk scores should be considered for estimating prognosis.[1]
The ESC specifies that the GRACE risk score is the most accurate for risk stratification.
In a retrospective study comparing the TIMI and GRACE scores, GRACE performed better in predicting mortality (in hospital and at 6 months).[101]
GRACE performed better than TIMI in a 2012 meta-analysis that included 18 validation cohorts (n=56,673) of people with NSTEMI (TIMI: c-statistic 0.54, 95% CI 0.52 to 0.57 for short-term studies and 0.67, 95% CI 0.62 to 0.71 for long-term studies; GRACE c-statistic 0.83, 95% CI 0.79 to 0.87 for short-term studies and 0.80, 95% CI 0.74 to 0.89 for long-term studies).[102]
GRACE has also been shown to perform better than subjective physician assessment for predicting mortality or myocardial infarction.[103][104]
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.
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 management depends on the patient’s clinical presentation and risk assessment. The UK National Institute for Health and Care Excellence and European Society of Cardiology (ESC) guidelines recommend dual antiplatelet therapy with aspirin plus a P2Y12 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 P2Y12 inhibitor if the coronary anatomy is unknown and invasive coronary angiography is planned within 24 hours.[1]
Further acute management led by the cardiology team will involve one of two options, depending on the risk assessment:[1][71]
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.
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 P2Y12 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.
Start (or increase the patient’s current) anti-anginal medication.[105]
Give a beta-blocker or a calcium-channel blocker first line.[105]
Ensure the patient has a short-acting nitrate for immediate relief of angina symptoms as needed.[94]
Discuss and offer support for lifestyle changes and modification of risk factors for CVD. These include:[22][94]
Healthy diet
Limiting alcohol consumption
Smoking cessation
Achieving and maintaining healthy weight
Physical activity
Management of hypertension. See Essential hypertension.
Give the following drug treatment (while taking into account any contraindications):
Dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor (after discussion with a cardiologist).[1][71]
Continue aspirin indefinitely unless the patient has hypersensitivity. Continue the P2Y12 inhibitor for up to 12 months[1][71] Check your local protocol when deciding which P2Y12 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 P2Y12 inhibitor may be used in these patients; the UK National Institute for Health and Care Excellence recommends clopidogrel.[71]
Long-term use of clopidogrel may be associated with reduced risk of non-fatal MI, and similar risk of all-cause mortality, stroke, and major-bleeding compared with aspirin in patients with pre-existing CVD.[106]
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 P2Y12 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 P2Y12 receptor inhibitor monotherapy after 1 month of dual antiplatelet therapy in patients with high bleeding risk
Abbreviated dual antiplatelet therapy strategies and de-escalation of dual antiplatelet therapy can be considered in patients at high risk of bleeding.[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 P2Y12 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.
An ACE inhibitor if the patient has heart failure with reduced left ventricular ejection fraction (LVEF), 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.
A statin. Patients with established coronary artery disease are at very high risk for cardiovascular events so consider statin treatment regardless of low-density lipoprotein cholesterol (LDL-cholesterol) levels. The aim is to reduce LDL-cholesterol by >50% from baseline and to achieve LDL-cholesterol <1.4 mmol/L (<54 mg/dL). Consider intensification of lipid-lowering therapy for patients who were on treatment before admission.[1]
Non-adherence to statin therapy and failure to achieve lipid targets is associated with an increased cardiovascular mortality after acute MI.[107] Patients should be counselled on the importance of medication adherence.
Target LDL-cholesterol is <1.4 mmol/L (<55 mg/dL) and a ≥50% LDL-cholesterol reduction from baseline. If these targets are not achieved on maximal statin therapy, add ezetimibe.[1][64]
A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor monoclonal antibody (e.g., evolocumab, alirocumab) may be added to maximal statin and ezetimibe therapy if the patient is at very high risk of future events and LDL-cholesterol targets are not achieved.[108][109][110] Treatment can be started during ACS admission or at outpatient follow-up 4-6 weeks later.
An aldosterone antagonist if the patient has heart failure with reduced LVEF (<40%).[1] Start this within 3-14 days of non-ST-elevation myocardial infarction and preferably after starting an ACE inhibitor.[71]
A sodium-glucose cotransporter-2 (SGLT2) inhibitor (e.g., dapagliflozin, empagliflozin) for patients with heart failure when they are clinically stable, regardless of the LVEF.[1][111][112]
For more information on management of stable angina see Stable ischaemic heart disease.
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