Acute coronary syndrome (ACS) is a medical emergency and requires immediate hospital admission. ACS is now classified mainly on the findings on the admission ECG and the results of serial cardiac troponin levels. ACS refers to a range of acute myocardial ischaemic states, which include:
- ST-elevation ACS (STE-ACS): patients present with acute chest pain and persistent (>20 minutes) ST-segment elevation. Most of these patients will develop an ST-elevation myocardial infarction (STEMI).
- Non-ST-elevation ACS (NSTE-ACS): patients present with acute chest pain but without persistent ST-segment elevation. The ECG shows persistent or transient ST-segment depression or T-wave inversion, flat T waves, pseudo-normalisation of T waves, or no ECG changes at presentation. NSTE-ACS is further divided into:
- Unstable angina: normal troponin levels.
- Non-ST-elevation myocardial infarction (NSTEMI): a rise in troponin levels.
This article refers mainly to unstable angina and NSTEMI. STEMI is discussed in the separate Acute Myocardial Infarction, Acute Myocardial Infarction Management, Complications of Acute Myocardial Infarction and Posterior Myocardial Infarct articles. There is also a separate Stable Angina article.
See also separate Epidemiology of Coronary Heart Disease article.
- The diagnosis of NSTEMI is more difficult to establish than STEMI and therefore its prevalence is harder to estimate.
- Coronary heart disease is the single biggest cause of death in the UK as well as being a major cause of premature mortality.
- Non-modifiable risk factors for atherosclerosis: increasing age, male, family history of premature coronary heart disease, premature menopause.
- Modifiable risk factors for atherosclerosis: smoking, diabetes mellitus (and impaired glucose tolerance), hypertension, dyslipidaemia (raised low-density lipoprotein (LDL) cholesterol, reduced high-density lipoprotein (HDL) cholesterol), obesity, physical inactivity.
- Consider non-atherosclerotic causes in younger patients or if there is no evidence of atherosclerosis: coronary emboli from sources such as an infected cardiac valve, coronary occlusion secondary to vasculitis, coronary artery spasm, cocaine use, congenital coronary anomalies, coronary trauma, increased oxygen requirement (eg, hyperthyroidism) or decreased oxygen delivery (eg, severe anaemia).
- The presentation of unstable angina and NSTEMI may be indistinguishable, and also indistinguishable from acute STEMI. NSTE-ACS can present in a variety of ways, including:
- Prolonged (longer than 20 minutes) anginal pain at rest.
- New-onset angina with limitation of daily activities.
- Recent destabilisation of previously stable angina, with moderate or severe limitation of daily activities.
- Post-myocardial infarction angina.
- Chest pain may be associated with sweating, nausea, vomiting, fatigue, shortness of breath and palpitations.
- Some patients, particularly the elderly and patients with diabetes, may not have chest pain. Patients from some ethnic groups may also present with atypical pains.
- Physical examination is focused on the assessment of cardiac function and circulatory stability and on excluding important differential diagnoses.
Assessment for possible acute coronary syndrome
See also the separate Cardiac-type Chest Pain Presenting in Primary Care article.
- Consider the history of the pain, any cardiovascular risk factors, history of coronary heart disease and any previous treatment, and previous investigations for chest pain.
- Symptoms that may indicate ACS include:
- Pain in the chest and/or other areas (eg, the arms, back or jaw) lasting longer than 15 minutes.
- Chest pain with nausea and vomiting, marked sweating and/or breathlessness, or haemodynamic instability.
- New-onset chest pain, or abrupt deterioration in stable angina, with recurrent pain occurring frequently with little or no exertion and often lasting longer than 15 minutes.
- The response to glyceryl trinitrate (GTN) should not be used to make a diagnosis and symptoms should not be assessed differently in men and women or among different ethnic groups.
See also the separate Chest Pain article.
- Cardiovascular: acute pericarditis, myocarditis, aortic stenosis, aortic dissection, pulmonary embolism.
- Respiratory: pneumonia, pneumothorax.
- Gastrointestinal: oesophageal spasm, gastro-oesophageal reflux disease, acute gastritis, cholecystitis, acute pancreatitis.
- Musculoskeletal chest pain.
It is essential to exclude a myocardial infarction with ST elevation for which immediate thrombolysis is indicated.
- 12-lead ECG:
- To confirm a cardiac basis for presentation and may show pre-existing structural or coronary heart disease (eg, left ventricular hypertrophy, Q waves).
- A normal or unchanged ECG does not exclude the possibility that chest pain is ischaemic in origin.
- Changes that may be seen during episodes of angina include transient ST-segment elevations (fixed changes suggest acute infarction).
- In unstable angina (and non-Q wave infarction), the ECG typically shows T-wave inversion or ST-segment depression' however, the ECG may be normal if some time has elapsed since the last episode of pain.
- Cardiac enzymes:
- Within the first six hours, the sensitivity of troponins is superior to CK-MB for the detection of myocardial infarction.
- Troponin I and T become detectable in serum three to six hours after infarction, peak at 12-24 hours, and remain raised for up to 14 days.
- Troponins are therefore usually tested six and 12 hours after the onset of pain.
- In patients with unstable angina, minor troponin elevations may identify patients at risk for subsequent cardiac events and death. Elevated troponin levels indicate an increased risk of mortality in both the short term and the long term. Patients with chest pain and elevated troponin levels should remain in hospital for further assessment, including an inpatient coronary angiogram.
- FBC may be useful in patients with suspected anaemia and as a baseline in view of use of anticoagulants; blood glucose, renal function and electrolytes, and TFTs. CRP as a marker of acute inflammation.
- Blood glucose: hyperglycaemia is common in people admitted to hospital with ACS. Hyperglycaemia at the time of admission with ACS is a powerful predictor of poorer survival and increased risk of complications while in hospital, regardless of whether or not the patient has diabetes.
- Echocardiography often demonstrates wall motion abnormalities due to ischaemia. May be useful in identifying precipitants for ischaemia - eg, ventricular hypertrophy and valvular disease.
- CXR may show complications of ischaemia (eg, pulmonary oedema), or explore alternative diagnoses - eg, pneumothorax, aortic aneurysm.
- Cardiac magnetic resonance (CMR) imaging can be useful for the assessment of function and perfusion and for the detection of scar tissue. CMR can also be useful to exclude or detect ACS, to assess myocardial viability and to detect myocarditis.
- Coronary angiography provides information on the presence and severity of coronary artery disease and therefore remains the gold standard.
As soon as the diagnosis of unstable angina or NSTEMI is made and aspirin and antithrombin therapy have been offered, individual risk of future adverse cardiovascular events should be assessed using an established risk scoring system that predicts six-month mortality. Risk is defined as:
- Low: up to 3%.
- Intermediate: above 3% and up to 6%.
- High: above 6%.
The National Institute for Health and Care Excellence (NICE) recommends the Global Registry of Acute Cardiac Events (GRACE) risk score.
Factors to use when assessing risk with an established scoring system include:
- Full clinical history, including age, previous myocardial infarction, previous percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).
- Physical examination, including blood pressure and heart rate.
- 12-lead resting ECG.
- Blood tests (such as troponin I or T, creatinine, glucose and haemoglobin).
The risk of bleeding should be assessed as well as relevant comorbidity before considering treatments and at each stage of management. Factors associated with high bleeding risk include advancing age, known bleeding complications, renal impairment and low body weight.
Treatment includes antithrombotic treatment, as well as coronary angiography followed by revascularisation if appropriate. The treatment of patients with NSTE-ACS is directed to alleviate pain and anxiety, prevent recurrences of ischaemia and prevent or limit progression to acute myocardial infarction.
- Compared to a conservative strategy, an invasive strategy (PCI or CABG surgery) is associated with reduced rates of refractory angina and rehospitalisation in the shorter term and myocardial infarction in the longer term. An invasive strategy is associated with a doubled risk of procedure-related heart attack and increased risk of bleeding and procedural biomarker leaks.
- Available evidence suggests that an invasive strategy may be particularly useful in those at high risk for recurrent events.
- However, in lower-risk patients, conservative management (initial intensive medical treatment followed by non-invasive risk assessment - eg, by exercise ECG) has been found to be as effective as early invasive management.
Immediate management of a suspected ACS
- Arrange urgent hospital admission (phone 999/112/911).
- Resuscitation as required.
- Pain relief: GTN and/or an intravenous opioid (use an antiemetic with opioids).
- Single loading dose of 300 mg aspirin unless the person is allergic.
- A resting 12-lead ECG - but don't delay transfer to hospital.
- Assess oxygen saturation, using pulse oximetry before hospital admission if possible. Give oxygen if oxygen saturation (SpO2) is less than 94% with no risk of hypercapnic respiratory failure; aim for SpO2 of 94-98% (aim for 88-92% for people with chronic obstructive pulmonary disease).
- Antiplatelet and anticoagulant therapy
- In the presence of ischaemic ECG changes or elevation of cardiac troponin, patients with an ACS should be treated immediately with both aspirin (300 mg loading dose) and ticagrelor (180 mg loading dose).
- Consider clopidogrel monotherapy for patients with aspirin hypersensitivity.
- Clopidogrel can also be used in combination with low-dose aspirin for up to 12 months following ACS.
- Prasugrel in combination with aspirin is recommended by NICE as an option for preventing atherothrombotic events in adults with ACS having primary or delayed PCI.
- Ticagrelor in combination with low-dose aspirin is recommended for up to 12 months as a treatment option in adults with ACS with:[3, 13]
- STEMI that cardiologists intend to treat with primary PCI; or
- NSTEMI; or
- Admission to hospital with unstable angina.
- Glycoprotein IIb/IIIa inhibitors:
- Consider eptifibatide or tirofiban for patients at intermediate or higher risk if angiography is scheduled within 96 hours of admission.
- Consider abciximab as an adjunct to PCI for patients at intermediate or higher risk who are not already receiving a glycoprotein inhibitor (GPI).
- Antithrombin therapy: anticoagulants are used in the treatment of NSTE-ACS to inhibit thrombin generation and/or activity, thereby reducing thrombus-related events.
- Offer fondaparinux to patients without a high bleeding risk unless angiography is planned within 24 hours of admission. Offer unfractionated heparin as an alternative to fondaparinux if angiography is likely within 24 hours of admission.
- Carefully consider the choice and dose of antithrombin in patients with a high bleeding risk.
- Consider unfractionated heparin, with dose adjusted to clotting function, for patients with creatinine above 265 μmol/L.
- Offer systemic unfractionated heparin (50-100 units/kg) in the cardiac catheter laboratory to patients on fondaparinux who are undergoing PCI.
- As an alternative to the combination of a heparin plus a GPI, consider bivalirudin for patients who are at intermediate or higher risk, who are not already receiving a GPI or fondaparinux and are scheduled for angiography within 24 hours of admission.
- As an alternative to the combination of a heparin plus a GPI, consider bivalirudin for patients undergoing PCI who are at intermediate or higher risk and are not already on a GPI or fondaparinux.
- Patients with NSTE-ACS should be assessed for risk (using the GRACE scoring system, as above) of cardiovascular event. If they are at medium to high risk they should be offered early in-hospital coronary angiography, possibly with GPIIb/IIIa inhibitor.
- If the patient is at low risk but symptoms are recurring, they should also be offered coronary angiography.
- The proportion of patients with NSTE-ACS undergoing CABG surgery during initial hospitalisation is about 10%. The benefit from bypass surgery is greatest when patients can be operated on after several days of medical stabilisation, depending on the individual risk.
- Other treatments:
- Nitrates (sublingual, oral or intravenous): for ongoing pain whilst waiting for more definitive procedures, and may overcome superimposed coronary artery spasm.
- Beta-blockers improve outcome and can reduce the severity and frequency of attacks.
- Calcium antagonists (eg, diltiazem, verapamil) are used for patients who cannot tolerate a beta-blocker, or are used in addition to a beta-blocker. Verapamil should not be combined with a beta-blocker.
- Angiotensin-converting enzyme (ACE) inhibitors reduce mortality and should be started when the patient is an inpatient unless contra-indicated.
- A Cochrane review found that initiation of statin therapy within 14 days following ACS does not reduce death, myocardial infarction, or stroke up to four months; however, it does reduce the occurrence of unstable angina at four months following ACS.
- Hyperglycaemia in patients admitted to hospital for an ACS should be managed by keeping blood glucose levels below 11.0 mmol/L while avoiding hypoglycaemia. A dose-adjusted insulin infusion with regular monitoring of blood glucose levels should be considered.
- All patients with hyperglycaemia after ACS and without known diabetes should be tested for HbA1c levels before discharge and fasting blood glucose levels no earlier than four days after the onset of ACS.
- After stabilisation, secondary risk reduction measures should be implemented. These measures include stopping smoking, continued aspirin therapy, management of hypertension if present, statins, ACE inhibitors and beta-blockers. If a patient was stabilised with medical treatment then it is likely they will undergo treadmill exercise testing.
- To detect and quantify inducible ischaemia, consider ischaemia testing before discharge for patients whose condition has been managed conservatively and who have not had coronary angiography.
- Assess left ventricular function in all patients who have had a myocardial infarction and consider assessing left ventricular function in all patients with unstable angina.
- Cardiac rehabilitation: rehabilitation and discharge planning.
- Secondary prevention: management of cardiovascular risk factors with lifestyle changes and drug therapy as indicated.
- Acute myocardial infarction.
- Cardiogenic shock.
- Ischaemic mitral regurgitation.
- Supraventricular arrhythmias: rare complication of ischaemia.
- Ventricular arrhythmias: simple and complex premature ventricular contractions and non-sustained ventricular tachycardia
- Atrioventricular nodal blockade: usually transient in setting of reversible ischaemia (treatment is guided by location of block and haemodynamic stability).
People with NSTE-ACS have a high incidence of recurrent myocardial ischaemia, a similar long-term outcome to those with STEMI, and a worse outcome than for people with unstable angina.
In-hospital death and re-infarction affect 5-10%. Despite optimal treatment with anti-ischaemic and antithrombotic drugs, death and recurrent myocardial infarction occur in another 5-10% of patients in the month after an acute episode. Factors associated with a poorer prognosis include:
- Advancing age.
- Presence and severity of ECG changes of ischaemia.
- Magnitude of rise in biomarkers of myocardial injury (eg, serum troponin).
- Left ventricular dysfunction, cardiogenic shock.
- Increased heart rate, arrhythmias (ventricular fibrillation, atrial fibrillation).
- Renal impairment.
- Diabetes mellitus.
- Cerebrovascular disease, peripheral arterial disease.
Any delay in arranging angiography for high-risk patients is associated with increased mortality and adverse outcomes.
- Smoking cessation.
- Dietary and exercise advice.
- Blood pressure, hyperlipidaemia and diabetes control.
- Compliance with medications, particularly aspirin.
- Comprehensive risk assessment, including exercise tolerance test for those at high risk and identification of structural heart disease (eg, left ventricular hypertrophy, aortic stenosis).
Further reading and references
2014 ESC/EACTS Guidelines on myocardial revascularization; The Task Force on Myocardial Revascularization of the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery (Aug 2014)
Acute coronary syndromes (including myocardial infarction); NICE Quality Standard, Sept 2014
Peters RJ, Mehta S, Yusuf S; Acute coronary syndromes without ST segment elevation. BMJ. 2007 Jun 16334(7606):1265-9.
2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation; European Society of Cardiology (August 2015)
Acute coronary syndrome; Scottish Intercollegiate Guidelines Network - SIGN (2016)
Chest pain of recent onset; NICE Clinical Guideline (March 2010, updated Nov 2016)
Hyperglycaemia in acute coronary syndromes; NICE Clinical Guideline (October 2011)
Unstable angina and NSTEMI; NICE Clinical Guideline (March 2010 - last updated November 2013)
Global Registry of Acute Cardiac Events (GRACE) ACS Risk Model; Center for Outcomes Research
TIMI Risk Scores; Cardiology.org
D'Ascenzo F, Biondi-Zoccai G, Moretti C, et al; TIMI, GRACE and alternative risk scores in Acute Coronary Syndromes: a meta-analysis of 40 derivation studies on 216,552 patients and of 42 validation studies on 31,625 patients. Contemp Clin Trials. 2012 May33(3):507-14. doi: 10.1016/j.cct.2012.01.001. Epub 2012 Jan 11.
Hoenig MR, Aroney CN, Scott IA; Early invasive versus conservative strategies for unstable angina and non-ST elevation myocardial infarction in the stent era. Cochrane Database Syst Rev. 2010 Mar 17(3):CD004815. doi: 10.1002/14651858.CD004815.pub3.
Conway Morris A, Caesar D, Gray S, et al; TIMI risk score accurately risk stratifies patients with undifferentiated chest pain presenting to an emergency department. Heart. 2006 Sep92(9):1333-4.
Prasugrel with percutaneous coronary intervention for treating acute coronary syndromes; NICE Technology Appraisal Guidance, July 2014
Ticagrelor for the treatment of acute coronary syndromes; NICE Technology Appraisal Guidance, October 2011
Vale N, Nordmann AJ, Schwartz GG, et al; Statins for acute coronary syndrome. Cochrane Database Syst Rev. 2014 Sep 19:CD006870. doi: 10.1002/14651858.CD006870.pub3.
Cohen M, Diez JE, Levine GN, et al; Pharmacoinvasive management of acute coronary syndrome: incorporating the 2007 ACC/AHA guidelines: the CATH (cardiac catheterization and antithrombotic therapy in the hospital) Clinical Consensus Panel Report--III. J Invasive Cardiol. 2007 Dec19(12):525-38
Swanson N, Montalescot G, Eagle KA, et al; Delay to angiography and outcomes following presentation with high-risk, non-ST-elevation acute coronary syndromes: results from the Global Registry of Acute Coronary Events. S Heart. 2009 Mar95(3):211-5. Epub 2008 Sep 18.
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