Updated Guidelines for Acute Coronary Syndromes

The Heart Foundation and the Cardiac Society of Australia and New Zealand have released the new Australian clinical guideline for diagnosing and managing acute coronary syndromes 2025. This new guideline replaces National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Australian clinical guidelines for the management of acute coronary syndromes 2016.

Acute coronary syndrome (ACS) includes acute myocardial infarction (AMI) and unstable angina. Around 160 Australians experience an acute coronary event each day and these events remain a leading cause of morbidity and mortality.

The new guideline contains updated evidence-based recommendations and practical advice that is intended to improve patient outcomes overall and reduce disparities in care for people experiencing ACS across Australia.

Changes relating to pharmacotherapy include new recommendations and guidance on secondary prevention measures, as follows:

• More detailed advice on post-discharge care (e.g. medicines and adherence strategies, vaccinations, mental health screening);
• Treatment algorithms to enable more tailored prescribing of antiplatelet and anticoagulation therapies;
• A new recommended treatment target for low density lipoprotein cholesterol (LDL-C) of <1.4 mmol/L and a reduction of at least 50% from baseline; and
• New recommendations on select medicines, including beta blockers and the PCSK9 inhibitors, alirocumab and evolocumab.

Vaccinations

Viral respiratory infections are a well-documented trigger for AMI. Various mechanisms have been proposed for this increased risk. The systemic inflammatory response to a viral infection may destabilise atherosclerotic plaques. These plaques contain inflammatory cells that can be activated by several cytokines present in a pro-inflammatory state. This can lead to activation of the coagulation cascade, thereby increasing the risk of AMI. Hypoxaemia associated with severe respiratory infections can also increase the risk of AMI. The reduced oxygen supply, coupled with the increased metabolic needs during systemic inflammation, can create an imbalance in oxygen supply and demand.

One study conducted in patients with angiographically confirmed AMI found a 17-fold increased risk of AMI within seven days of a respiratory infection. Other studies looking at individual viruses found an elevated risk for influenza, respiratory syncytial virus, and COVID-19.

The relationship between viral infections and cardiovascular events suggests that vaccination could play a role in preventing AMI in patients with cardiovascular disease. Evidence for the benefits of vaccination in this setting is particularly strong for influenza. Vaccination against influenza has also been shown to reduce the risk of further cardiac complications following ACS. The evidence demonstrates that influenza vaccination is safe and effective when administered within 72 hours of an invasive coronary procedure or hospitalisation for AMI.

The benefits of vaccination in these patients likely go beyond prevention of cardiovascular events. People with cardiovascular disease are at higher risk of severe viral infection, making preventative measures particularly important.

The guidelines recommend:

• Annual influenza vaccination
• Pneumococcal vaccination per the immunisation schedule
• RSV vaccination for patients with coronary artery disease (CAD) who are 60 years of age or older.
• Consideration of additional doses of COVID-19 vaccine for all patients with chronic cardiac conditions.

Antiplatelet therapy

Some of the recommendations for antiplatelet therapy have been updated. The recommended duration for dual antiplatelet therapy (DAPT) in patients discharged following an ACS is now:

• High ischaemic and/or low bleeding risk
  • DAPT for 6-12 months.
  • P2Y₁₂ inhibitor preferred over aspirin for continuation of long-term therapy.
  • Long-term (>12 months) DAPT may be considered for patients who remain at high ischaemic and low bleeding risk.
• Low ischaemic risk and/or high bleeding risk
  • DAPT may be ceased at 1-3 months, with single antiplatelet therapy continued.
• Indication for long-term oral anticoagulant therapy (e.g. atrial fibrillation)
  • Continue anticoagulant and DAPT for 1-4 weeks, then cease aspirin.
  • Cease antiplatelet therapy at 6-12 months and continue anticoagulant alone.

Available P2Y₁₂ receptor inhibitors are:

• Clopidogrel;
• Prasugrel; and
• Ticagrelor.

The choice of P2Y₁₂ receptor inhibitor will depend on different patient factors. Ticagrelor and prasugrel are considered more potent than clopidogrel and are also associated with less interpatient variability. Clopidogrel is preferred for older adults with higher bleeding risk. Some patients may prefer the convenience of once daily dosing with clopidogrel and prasugrel, compared to ticagrelor which is taken twice a day.

Gastroprotection

A proton pump inhibitor (PPI) is recommended for patients receiving DAPT who have a high risk of gastrointestinal bleeding and for patients receiving triple antithrombotic therapy.

Available PPIs are:

• Esomeprazole;
• Lansoprazole;
• Omeprazole;
• Pantoprazole; and
• Rabeprazole.

All PPIs have similar safety and efficacy. However, there are some differences in their potential to cause drug interactions. For example, esomeprazole and omeprazole inhibit CYP2C19 and may increase the plasma levels of medications that are substrates of this enzyme (e.g. warfarin, citalopram, diazepam).

Lipid-modifying therapy

A reduction in LDL-C of 1.0 mmol/L can reduce the risk of AMI, stroke, coronary revascularisation and vascular death. Statins are the first-line lipid-modifying agents. They have established efficacy and a low rate of serious adverse effects.

The guidelines recommend the initiation of statin therapy prior to hospital discharge following ACS. If the patient was already on lipid-lowering therapy, this should be reviewed with consideration of intensifying therapy. Statin therapy should be continued indefinitely at the highest tolerated dose, unless contraindicated or the patient is not tolerant.

Available statins are:

• Atorvastatin;
• Fluvastatin;
• Pravastatin;
• Rosuvastatin; and
• Simvastatin.

All statins are associated with a reduced risk of cardiovascular events. However, it is the extent of LDL-C reduction that is important, and this is determined by the potency of the statin and the dose used. High-potency statins, such as atorvastatin and rosuvastatin, are preferred following an ACS.

One other consideration when selecting a statin is the potential for drug interactions. Fluvastatin, pravastatin and rosuvastatin are associated with fewer interactions compared to atorvastatin and simvastatin.

Additional non-statin therapies are often required to achieve target lipid levels. Medications that may be added to statin therapy include:

• Ezetimibe;
• PCSK9 inhibitors. This class includes alirocumab, evolocumab, and inclisiran. These medications are administered by subcutaneous injection every 2-4 weeks (alirocumab and evolocumab) or up to six-monthly (inclisiran); or
• Icosapent ethyl (for elevated triglyceride levels).

Beta blocker therapy

The guidelines recommend the use of a beta blocker for patients with ACS and left ventricular (LV) impairment. In this cohort, they are associated with a reduced risk of recurrent AMI. Their efficacy in patients with preserved ejection fraction is less clear.

For patients with confirmed LV impairment, the guidelines recommend use of a beta blocker with proven benefit in heart failure with reduced ejection fraction. This includes bisoprolol, carvedilol, metoprolol, and nebivolol.

Renin-angiotensin antagonist therapies

Angiotensin converting enzyme (ACE) inhibitors are associated with a reduced risk of early mortality and further cardiovascular events following AMI. Angiotensin receptor blockers (also known as sartans) exhibit similar effects to ACE inhibitors. However, angiotensin receptor–neprilysin inhibitors (i.e. sacubitril + valsartan) have not demonstrated any benefit in this population.

Adjunct medications

The new version of the guidelines also contains recommendations regarding colchicine and semaglutide. These medications were not included in the previous version of the guidelines.

Colchicine

Colchicine may reduce the risk of recurrent ischaemic events in ACS by reducing the persistent inflammation that occurs in these patients. Studies have evaluated doses ranging from 0.5 mg to 1.0 mg per day. A recent meta-analysis suggests that doses at the lower end of this range may be effective in reducing recurrent ischaemic events. Higher doses are associated with an increased risk of gastrointestinal adverse events and may not offer any additional benefits. However, colchicine was not associated with a significant reduction in all-cause mortality or cardiovascular death. Further research is required to clarify the role of colchicine post-ACS.

The most common side effects are gastrointestinal, e.g. diarrhoea, nausea, vomiting, and abdominal pain. Colchicine is metabolised by CYP3A4 and is a substrate of P‑glycoprotein. Therefore, combination with CYP3A4 inhibitors (e.g. amiodarone, ciclosporin, ticagrelor, grapefruit juice) or P‑ glycoprotein inhibitors (e.g. carvedilol, clarithromycin, verapamil) may increase colchicine concentration. This can lead to increased adverse effects and is particularly important to consider in patients with renal impairment.

Semaglutide

For people with ACS who are overweight or obese, a glucagon-like peptide-1 (GLP-1) receptor agonist may improve outcomes. The SELECT trial demonstrated that the cardiovascular benefits associated with semaglutide in people with diabetes were also seen in patients without diabetes.

The SELECT trial enrolled people without diabetes who were overweight or obese and had pre-existing cardiovascular disease (defined as previous AMI or stroke, or symptomatic peripheral arterial disease). Participants were randomly assigned to receive weekly semaglutide or placebo. Semaglutide was found to be superior to placebo in reducing the incidence of non-fatal AMI and stroke as well as death from cardiovascular causes.

Semaglutide is not currently subsidised on the Pharmaceutical Benefits Scheme (PBS) for people without diabetes.

Further information

The Heart Foundation provides a range of useful resources for healthcare professionals and free access to the MyHeart MyLife support program for patients.