Management of acute coronary syndromes

Recommendations

Major Recommendations

Notes from the National Guideline Clearinghouse (NGC)

• In March 2008, the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand released an addendum to their 2006 guidelines for the management of acute coronary syndrome, highlighting evidence "that strengthens the recommendations in the guidelines or provides alternatives to current recommended practice that should be considered based on the circumstances of the individual patient and setting." This new information is presented under the heading "2008 Addendum: Implications of the Findings."
• The National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand released an additional addendum in August 2011. This addendum "summarises clinical trial evidence published since 2007 that is relevant to the recommendations contained in the Heart Foundation's Guidelines for the management of acute coronary syndromes 2006 and 2007 addendum to the National Heart Foundation of Australia/Cardiac Society of Australia and New Zealand Guidelines for the management of acute coronary syndromes 2006. These recommendations are directed at the management of patients with spontaneous acute coronary syndromes, rather than those occurring as a result of other conditions (e.g., anaemia or thyrotoxicosis) where management may be directed at the underlying cause. This new information is presented under the heading "2011 Addendum."
• Definitions for the strength of recommendations and levels of evidence for the 2011 addendum are provided at the end of the "Major Recommendations" field.

2006 Guideline
The recommendations that follow are from the 2006 guideline's "Summary of Key Recommendations"; detailed graded recommendations can be found in the original guideline document.
Systems of Care for Patients with Acute Coronary Syndromes

• Effective systems of care are required to deliver optimal care for patients with acute coronary syndromes (ACS), particularly in rural and remote areas.
• Systems of care should be regionally based, and have formal links with specialist centres for consultation and acute interhospital transfer.
• Systems should include appropriate monitoring, feedback, and quality improvement components.
• Clinical decisions about care and transfer should take into account patients' cultural and personal beliefs and wishes.

New Acute Coronary Syndrome Terminology and Implications for Diagnosis

• It is important to establish an initial working diagnosis to guide clinical decision making.
• New definitions of myocardial infarction, based heavily on the presence of cardiac biomarkers, have implications for coding and epidemiological studies. However, clinically they do not influence the indications for ongoing prevention therapies.
• Use of the ACS Dataset (part of the National Health Data Dictionary) can facilitate the collection of data relating to the presentation and management of ACS that can be compared and collated within and between health care providers.

Acute Management of Chest Pain

• People experiencing symptoms of an ACS should seek help promptly and activate emergency medical services.
• The most important initial need is access to a defibrillator to avoid early cardiac death resulting from reversible arrhythmias.
• Aspirin should be given early (i.e., by emergency or ambulance personnel) unless already taken or contraindicated.
• Oxygen should be given, as well as glyceryl trinitrate and intravenous morphine as required.
• As a minimum, medical facilities receiving patients should be given warning of incoming patients in whom there is a high suspicion of an ACS—particularly ST-segment-elevation myocardial infarction (STEMI)—or whose condition is unstable.
• Where appropriate, a 12-lead electrocardiogram (ECG) should be taken en route and transmitted to a medical facility.
• Where formal protocols are in place, prehospital treatment (including fibrinolysis in appropriate cases) should be facilitated.

Investigations

• The ECG is the sole test required to select patients for emergency reperfusion (fibrinolytic therapy or direct percutaneous coronary intervention [PCI]).
• Patients with STEMI who present within 12 hours of the onset of ischaemic symptoms should have a reperfusion strategy implemented promptly.
• Patients with a suspected ACS without ST-segment elevation on ECG should undergo further observation and investigation to rule out other diagnoses, enable risk stratification, and determine the most appropriate treatment strategy.
• Patients whose ECG and cardiac marker levels are normal after a suitable period of observation should, where practicable, undergo provocative testing (e.g., stress test) before discharge.

Management of Patients with ST-Segment-Elevation Myocardial Infarction
Adjuvant Therapy in Association with Reperfusion

• All patients undergoing reperfusion therapy for STEMI (PCI or fibrinolysis) should be given aspirin and clopidogrel unless these are contraindicated.
• Antithrombin therapy should be given in combination with PCI or fibrinolytic therapy with fibrin-specific fibrinolytic agents, but antithrombin therapy in conjunction with streptokinase is optional.
• It is reasonable to use abciximab with primary PCI, but glycoprotein (GP) IIb/IIIa inhibitors should generally be avoided with full or reduced doses of fibrinolytic therapy.

Choice of Reperfusion Strategy

• Time delay (both to first medical contact and potential PCI or fibrinolytic therapy) plays a major role in determining best management of STEMI.
• In general, PCI is the treatment of choice, providing it can be performed promptly by a qualified interventional cardiologist in an appropriate facility.
• In general, the maximum acceptable delay from presentation to balloon inflation is:
  • 60 minutes if a patient presents within 1 hour of symptom onset; or
  • 90 minutes if a patient presents later
  Note: For patients who present late (between 3 and 12 hours after symptom onset) to a facility without PCI capability, it is appropriate to consider transfer for primary PCI if balloon inflation can be achieved within 2 hours (including transport time).
  
• All PCI facilities should be able to perform angioplasty within 90 minutes of patient presentation.
• Fibrinolysis should be considered early if PCI is not readily available, particularly in rural and remote areas.
• When there are major delays to hospitalisation (i.e., more than 30 minutes), prehospital fibrinolysis should be considered.
• Reperfusion is not routinely recommended in patients who present more than 12 hours after symptom onset and who are asymptomatic and haemodynamically stable.

Choice of Fibrinolytic Agent

• Second-generation fibrin-specific fibrinolytic agents that are available as a bolus (i.e., reteplase, tenecteplase) are the fibrinolytics of choice.
• These agents should be available at all centres where fibrinolysis may be required.
• Streptokinase is an inappropriate choice in Aboriginal and Torres Strait Islander patients, or in patients with previous exposure to the drug.

Transfer after STEMI

• Patients who have had STEMI should be considered for early transfer to a tertiary cardiac centre with PCI facilities and links to cardiac surgical facilities.
• If immediate transfer is not possible, patients should be transferred or referred as soon as is practicable for assessment of need for revascularisation (through PCI or coronary artery bypass grafting).

Management of Patients with Non-ST-Segment-Elevation Acute Coronary Syndromes

• All patients with non-ST-segment-elevation acute coronary syndromes (NSTEACS) should have their risk stratified to direct management decisions (see page 20 in the original guideline document for stratification criteria).
• All patients with NSTEACS should be given aspirin, unless contraindicated.
• High-risk patients with NSTEACS should be treated with aggressive medical management (including aspirin, clopidogrel, unfractionated heparin or subcutaneous enoxaparin, intravenous tirofiban or eptifibatide and a beta-blocker), and arrangements should be made for coronary angiography and revascularisation, except in those with severe comorbidities.
• Intermediate-risk patients with NSTEACS should undergo an accelerated diagnostic evaluation and further assessment to allow reclassification as low or high risk.
• Low-risk patients with NSTEACS, after an appropriate period of observation and assessment, may be discharged on upgraded medical therapy for outpatient follow up.

Long-term Management after Control of Myocardial Ischaemia

• Before discharge, patients with an ACS should be initiated on a medication regimen, including antiplatelet agent(s), beta-blocker, angiotensin-converting enzyme inhibitor, statin, and other therapies as appropriate.
• Implantable cardiac defibrillators should be considered in some patients who, despite optimal medical therapy, have persistently depressed left ventricular function more than 6 weeks after STEMI.
• Patients should be given advice on lifestyle changes that will reduce the risk of further coronary heart disease (CHD) events, including smoking cessation, nutrition, alcohol, physical activity, and weight management as relevant.
• All patients should have access to, and be actively referred to, comprehensive ongoing prevention and cardiac rehabilitation services.
• All patients should be provided with a written action plan for chest pain.
• Depression and CHD frequently coexist, and in patients with CHD, the presence of depression is more likely to lead to poorer outcomes. Social isolation and lack of social support are also associated with worse outcomes. All patients with CHD should be assessed for depression and level of social support.

2008 Addendum: Implications of the Findings
Reperfusion and Revascularisation for ST-Segment Elevation Myocardial Infarction
Rescue PCI

• The evidence for rescue PCI has strengthened since the development of the 2006 guidelines.
• Patients who receive fibrinolytic therapy and have not reperfused by 90 minutes should be considered for rescue PCI, which optimally should be performed within 12 hours. Transfer between facilities may be necessary to achieve this, and systems need to be in place to facilitate transfer of appropriate patients. If it is not possible for transfer within the 12-hour window, then transfer can be delayed if the patient is asymptomatic.

Revascularisation
Patients in whom the infarct-related artery is completely occluded do not benefit from re-opening the artery routinely if this occurs more than 24 hours after the initial event. If patients are symptomatic, revascularisation may be considered.
Antiplatelet and Antithrombin Therapy
Recent evidence, while providing additional information on outcomes for individual agents, does not provide conclusive evidence of the superiority of one agent over another, nor of one combination of therapies over another. The risks and benefits of these therapies and strategies should be evaluated individually in each patient.
Antithrombin Therapy for Acute STEMI
Enoxaparin and fondaparinux are appropriate antithrombin agents and may be considered for use in patients with STEMI.
Antithrombin Therapy for NSTEACS

• Fondaparinux and bivalirudin, both currently not licensed for upstream therapy of NSTEACS, may be preferable alternatives to standard therapy with unfractionated heparin or low molecular weight heparin with a GP IIb/IIIa inhibitor for patients with high-risk NSTEACS, particularly where there is an increased risk of bleeding. The selection of the most appropriate upstream therapy may best be determined for any individual patient from their risk of ischaemia versus bleeding.
• Fondaparinux may be particularly useful in patients for whom invasive management is significantly delayed or those not suitable for invasive management.
• Bivalirudin has the advantage of monotherapy for both upstream and procedural administration at the time of PCI, and therefore may be particularly useful in patients planning to have an early invasive intervention.

Antiplatelet Therapy for NSTEACS

• GP IIb/IIIa inhibition with abciximab reduces adverse cardiac events in biomarker-positive NSTEACS patients undergoing PCI who have been pretreated with clopidogrel. Pretreatment with high-dose clopidogrel is not an adequate alternative to abciximab among biomarker-positive NSTEACS patients.
• A deferred in-lab initiation approach to the use of intravenous GP IIb/IIIa inhibitors (particularly with abciximab) may be preferable to short-term (median 4 hours) upstream administration in patients presenting with high-risk NSTEACS.

2011 Addendum
Investigation: Serum Troponin Measurement
Implications of the Findings
Previous Recommendations
The 2006 Guidelines advised that serum troponin levels be measured on admission to the emergency department (ED). This recommendation still applies.
The 2006 Guidelines recommended that, if the initial troponin test is negative, it should be repeated at least 8 hours after the last episode of pain or other symptoms of coronary insufficiency. (When used in this way, troponin assays have a high sensitivity for detecting myocardial infarction [MI], but levels may be normal in other presentations of ACS.) This recommendation still applies when using standard-sensitivity troponin assays.
New Recommendations

1. Where available, high sensitivity troponin assays should be used in preference to conventional assays. [Grade of recommendation N/A]
2. When using high sensitivity troponin assays for the identification of patients at increased risk (see Recommended protocol in the original guideline document):
   • A test should be interpreted as positive if level is ≥99th centile for reference population OR there is a change of >50% above an initial baseline level. A positive finding identifies patients at increased risk, but does not provide definitive evidence of MI. A positive troponin result should be followed up by a search for an alternative plausible diagnosis and/or cardiac consultation if ACS is suspected in the context of the clinical presentation. [Consensus recommendation]
   • At 3 hours after presentation, a test should be interpreted as negative if level is <99th percentile AND change from baseline is <50% (with at least one of these assays having been performed >6 hours from symptom onset). A negative test in this circumstance may be used in an "early rule-out ACS" strategy to enable earlier functional or anatomic testing for symptomatic coronary artery disease. [Grade C recommendation; Evidence level III]
3. If the local pathology laboratory cannot provide troponin results within 60 min, point-of-care testing should be performed. [Grade of recommendation N/A]

Choice of Reperfusion Therapy for STEMI
Implications of the Findings
Previous Recommendations
The 2006 Guidelines indicated that undertaking immediate PCI after full-dose fibrinolysis, regardless of reperfusion status (also known as facilitated PCI) could not be recommended at the time of writing.
New Recommendations

1. Consider early routine angiography and revascularisation amongst patients receiving fibrinolysis, regardless of the success of pharmacologic reperfusion. [Grade A recommendation, Evidence level I]
2. Antiplatelet therapies should be continued for 12 months for all stented patients. [Grade A recommendation, Evidence level II]
3. The use of mechanical thrombectomy techniques to reduce thrombus burden during primary PCI should be considered. [Grade A recommendation, Evidence level I]

Antithrombotic Therapy for STEMI
Implications of the Findings
Previous Recommendations
The 2006 Guidelines recommended that:

• Antithrombin therapy with unfractionated (UF) heparin should be used in conjunction with PCI and fibrinolysis for patients with STEMI.
• It is reasonable to use abciximab with primary PCI.
• GP IIb/IIIa inhibitors should not be used with full or reduced doses of fibrinolytic therapy.

The 2007 Addendum recommended that enoxaparin and fondaparinux were appropriate antithrombin agents for use in patients with STEMI.
New Recommendations

1. Amongst patients with STEMI undergoing primary PCI, the use of bivalirudin can be considered as an alternative to heparin and GP IIb/IIIa inhibitors. [Grade B recommendation; Evidence level II]
2. Amongst patients undergoing primary PCI for reperfusion for STEMI or revascularisation for ACS, a high-dose clopidogrel regimen (600 mg oral bolus and 150 mg daily for 7 days, then 75 mg/day for at least 12 months) should be considered. [Grade B recommendation, Evidence level II]
3. In patients undergoing PCI, the use of an oral antiplatelet agent (prasugrel and ticagrelor) should be considered as an alternative to clopidogrel for subgroups at high risk of recurrent ischaemic events (e.g., those with diabetes, stent thrombosis, recurrent events on clopidogrel or a high burden of disease on angiography). Careful assessment of bleeding risk should be undertaken before using these agents. [Grade B recommendation; Evidence level II]

Antithrombotic Therapy for NSTEACS
Implications of the Findings
Previous Recommendations
The 2006 Guidelines recommended use of heparin or subcutaneous enoxaparin until angiography, or for 48–72 hours, for those with high-risk NSTEACS.
The 2007 addendum indicated that fondaparinux and/or bivalirudin (both of which were then unlicensed for upstream therapy for NSTEACS), may be preferable alternatives to standard therapy with UF heparin or low-molecular-weight heparin (LMWH) with a GPIIb/IIIa inhibitor for patients with high-risk NSTEACS, particularly in patients with an increased risk of bleeding.
New Recommendations
A new paradigm for the management of patients with high-risk NSTEACS is now recommended. Management decisions must take into consideration the balance between ischaemic and bleeding risk for the individual patient.

1. For all patients with high-risk NSTEACS, consider methods to reduce bleeding risk. [Grade A recommendation, Evidence level I]
   • Titrate antithrombotic agents to optimal dose for weight and renal function. [Grade A recommendation, Evidence level I]
   • Avoid upstream GP IIb/IIIa inhibitors unless there is recurrent ischaemia on standard medical therapy. [Grade B recommendation, Evidence level II]
   • Consider radial access in preference to femoral access for PCI, but be mindful that this may be used as a conduit for surgery (coronary artery bypass graft [CABG]). [Grade B recommendation, Evidence level III]
   • During PCI, avoid right heart catheterisation and intra-aortic balloon pulsation unless indicated, and avoid prolonged procedure times. [Grade C recommendation, Evidence level III]
2. For all patients with high-risk NSTEACS, assess bleeding risk individually according to the number and severity of bleeding risk factors (see Bleeding risk in ACS, below). [Grade A recommendation, Evidence level II]
3. Assign a management strategy according to assessed individual bleeding risk: Use a "standard" strategy for patients at low risk of bleeding:
   
   • Choose the most effective anti-platelet regimen (e.g., prasugrel or ticagrelor). [Grade A recommendation, Evidence level I], and use fast-acting agents or multiple agents, as required, to control ischaemia rapidly. [Grade B recommendation, Evidence level II]

Use a "priority low-bleeding" strategy in patients at high risk of bleeding:

• Use antithrombotic agents with a lower bleeding risk, e.g.:
  • Clopidogrel in preference to prasugrel. [Grade B recommendation, Evidence level II]
  • (In the context of a non-invasive strategy) fondaparinux in preference to enoxaparin. [Grade B recommendation, Evidence level II]
  • (In the context of an invasive strategy) bivalirudin in preference to enoxaparin. [Grade B recommendation, Evidence level II]
• Minimise the number of agents used. [Grade B recommendation, Evidence level II]
• When additional agents are needed, consider substituting rather than adding them. [Grade B recommendation, Evidence level II]
• Consider shorter-acting or reversible agents, e.g., bivalirudin. [Grade B recommendation, Evidence level II]
• Avoid the use of GP IIb/IIIa inhibitors, if possible. [Grade B recommendation, Evidence level II]

Bleeding Risk in ACS
Implications of the Findings
Previous Recommendations
The 2006 Guidelines specify the following contraindications to fibrinolysis based on bleeding risk:

• Full-dose GP IIb/IIIa inhibitors with fibrinolytic therapy, particularly in the elderly
• Active bleeding or bleeding diathesis (excluding menses)
• Significant closed head or facial trauma within 3 months
• Suspected aortic dissection (including new neurological symptoms)
• Current use of anticoagulants (risk of bleeding is positively correlated with international normalised ratio)
• Non-compressible vascular punctures
• Recent major surgery (<3 weeks)
• Traumatic or prolonged (>10 min) cardiopulmonary resuscitation
• Recent (within 4 weeks) internal bleeding (for example, gastrointestinal or urinary tract haemorrhage)
• Active peptic ulcer

These recommendations still apply in addition to new recommendations.
New Recommendations

1. The following risk factors should be considered when assessing bleeding risk and when choosing anti-thrombotic therapies in patients with ACS [Grade B recommendation, Evidence level II]:
   • Age >75 years
   • Female sex
   • History of bleeding
   • History of stroke or transient ischaemic attack (TIA)
   • Creatinine clearance rate <60 mL/min
   • Diabetes
   • Heart failure
   • Tachycardia
   • Blood pressure <120 mmHg or >180 mmHg
   • Peripheral vascular disease
   • Anaemia
   • Concomitant use of a GP IIb/IIIa inhibitor
   • Administration of enoxaparin 48 hours prior to intervention
   • Switching between UF heparin and enoxaparin
   • Procedural factors associated with increased risk (femoral artery versus radial artery access, prolonged procedure, intra-aortic balloon pulsation, right heart catheterisation)

Oxygen Therapy for Patients with ACS
Implications of the Findings
Previous Recommendation
The 2006 Guidelines recommended administration of oxygen in transit and on arrival to hospital for patients with suspected ACS. This recommendation has been superseded.
New Recommendation

1. The routine use of supplemental oxygen is not recommended. [Grade C recommendation, Evidence level I]
2. Oxygen therapy is indicated for patients with hypoxia (oxygen saturation <93%) and those with evidence of shock, to correct tissue hypoxia. In the absence of hypoxia, the benefit of oxygen therapy is uncertain, and in some cases oxygen therapy may be harmful. [Consensus recommendation]

System Factors
Implications of the Findings
Timely reperfusion remains a key treatment objective in the management of STEMI.
Previous Recommendation
The 2006 Guidelines stated that local approaches to reperfusion depend on the specific local resources available for assessment, transfer, and delivery of care.
New Recommendations

1. System-based approaches to deliver timely reperfusion should be undertaken at local level. Establishment of clinical networks and efficient protocols to maximise the proportion of patients receiving timely reperfusion should be considered. [Grade B recommendation; Evidence level III-1]
2. Routine audit should be integrated into all clinical services that provide care to patients with ACS. [Grade B recommendation; Evidence level III]
3. In the absence of ready access to primary PCI services, systems should be developed to train local general practitioners and other health workers to initiate fibrinolysis in patients with STEMI, to maintain practitioners' skills, and to ensure practitioners are supported by ready access to expert cardiology consultation. [Recommendation grade N/A]

Definitions:
2011 Addendum Grades of Recommendations
A. Body of evidence can be trusted to guide practice
B. Body of evidence can be trusted to guide practice in most situations
C. Body of evidence provides some support for recommendation(s) but care should be taken in its application
D. Body of evidence is weak and recommendation must be applied with caution
N/A. Not applicable—recommendation cannot be graded
2011 Addendum Levels of Evidence
Levels of evidence were rated according to current National Health and Medical Research Council classifications, available at the National Health and Medical Research Council Web site.

Clinical Algorithm(s)

2006 Guideline
Clinical algorithms are provided in the original 2006 guideline document for the following:

• Defining acute coronary syndromes over time: presentation to final diagnosis
• Hospital management of ST-segment-elevation myocardial infarction (STEMI)
• Prehospital management of STEMI
• Treatment strategies for patients with non-ST-segment elevation acute coronary syndromes (NSTEACS), based on risk stratification
• Implantable cardiac defibrillator (ICD) implantation after STEMI: proposed management
• Emergency department/cardiac care unit (CCU) guidelines for the management of acute coronary syndromes

2011 Addendum
An algorithm for incorporating a high sensitivity troponin into the work-up of patients with suspected acute coronary syndrome (ACS) is provided in the 2011 addendum document.

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of evidence supporting the recommendations is specifically stated for selected recommendations in the original guideline document and for all recommendations in the 2011 addendum.

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Accurate diagnosis and appropriate management of acute coronary syndromes

Potential Harms

2006 Guideline

• Enoxaparin may be used in conjunction with fibrin-specific fibrinolytic agents, but care should be taken in patients who are aged over 75 years or who have renal dysfunction, as dose adjustment is necessary. Also, in patients receiving fibrinolysis for ST-segment-elevation myocardial infarction (STEMI), the use of enoxaparin is associated with an increase in episodes of major bleeding.
• Full-dose glycoprotein (GP) IIb/IIIa inhibitors should be avoided with fibrinolytic therapy as there is evidence of excessive bleeding (including intracranial haemorrhage) with this combination.
• Streptokinase should not be given to patients with previous exposure (more than 5 days ago) to the drug. There is also evidence that streptokinase may be less effective in Aboriginal and Torres Strait Islander peoples because of the high levels of skin infection (and thus streptococcal antibodies), particularly in remote populations.
• Side effects associated with streptokinase include hypotension and allergy.

Contraindications

Contraindications

Contraindications and Cautions for Fibrinolysis Use in ST-segment-elevation Myocardial Infarction
Absolute Contraindications
Risk of Bleeding

• Active bleeding or bleeding diathesis (excluding menses)
• Significant closed head or facial trauma within 3 months
• Suspected aortic dissection (including new neurological symptoms)

Risk of Intracranial Haemorrhage

• Any prior intracranial haemorrhage
• Ischaemic stroke within 3 months
• Known structural cerebral vascular lesion (e.g., arteriovenous malformation)
• Known malignant intracranial neoplasm (primary or metastatic)

Relative Contraindications
Risk of Bleeding

• Current use of anticoagulants: the higher the international normalised ratio (INR), the higher the risk of bleeding
• Non-compressible vascular punctures
• Recent major surgery (<3 weeks)
• Traumatic or prolonged (>10 minutes) cardiopulmonary resuscitation
• Recent (within 4 weeks) internal bleeding (e.g., gastrointestinal or urinary tract haemorrhage)
• Active peptic ulcer

Risk of Intracranial Haemorrhage

• History of chronic, severe, poorly controlled hypertension
• Severe uncontrolled hypertension on presentation (>180 mmHg systolic or >110 mmHg diastolic)
• Ischaemic stroke more than 3 months ago, dementia, or known intracranial abnormality not covered in contraindications

Other
Pregnancy