Secondary prevention of acute coronary syndromes: a summary of the new 2025 Australian guideline

SUMMARY

Acute coronary syndromes (ACS) remain a significant cause of disability and death in Australia. Following an initial acute coronary event, there is a significant risk of recurrence, particularly in the first 90 days.

In April 2025, the National Heart Foundation of Australia and the Cardiac Society of Australia and New Zealand launched a new Australian clinical guideline for diagnosing and managing ACS The guideline includes recommendations for the secondary prevention of ACS.

Pharmacotherapies for secondary prevention of ACS include antiplatelet and anticoagulant drugs, lipid-modifying therapy, beta blockers and renin–angiotensin antagonist therapies, plus – in select groups – colchicine and other therapies. Vaccination against influenza and other respiratory pathogens is recommended.

Nonpharmacological interventions include cardiac rehabilitation, healthy behaviour changes and screening for mental health conditions. The importance of providing strategies to support adherence to long-term therapies is also emphasised.

 

Introduction

The risk of recurrence and cardiovascular mortality following an acute coronary syndrome (ACS) has been estimated at 12.6% at 1 year, with half of these events occurring within 90 days following the first myocardial infarction (MI).¹ Implementation of effective secondary prevention measures is critical to reducing the risk of repeat events and improving cardiovascular outcomes.²

Despite the clear benefits, uptake of secondary prevention measures post-ACS is suboptimal, with persistence diminishing over time. While it is estimated that 89% of Australians with ACS are taking most of the guideline-recommended drugs at hospital discharge, this declines to 78% at 6 months and 66% at 2 years.³ The implications of nonadherence to prescribed drugs following an ACS are significant, including an increased risk of unplanned readmission.⁴ Likewise, at 6 months post-ACS, only 38% of people have attended cardiac rehabilitation,³ despite these programs having consistently been shown to reduce the risk of MI recurrence and improve quality of life.⁵

General practitioners (GPs) play a critical role in optimising secondary prevention following an ACS, in conjunction with cardiologists, allied health and cardiac rehabilitation health professionals. Implementation of strategies available to general practice are also central to this, such as GP chronic condition management plans and home medicines reviews.

A new Australian clinical guideline for diagnosing and managing ACS was launched in April 2025, developed by the National Heart Foundation of Australia in collaboration with the Cardiac Society of Australia and New Zealand.⁶ This article describes key recommendations from the recovery and secondary prevention section of the guideline, with a focus on pharmacotherapies.

 

Pharmacotherapies for secondary prevention of acute coronary syndrome

Antiplatelet therapy

Antiplatelet therapy is a well-established evidence-based secondary prevention strategy. Following an ACS, treatment starts with dual antiplatelet therapy (DAPT) for a period, before switching to single antiplatelet therapy. The 2025 guideline emphasises tailoring the duration of DAPT based on the individual's ischaemic and bleeding risks (Figure 1). Ischaemic risk is determined by factors including age, presentation with ST-elevation myocardial infarction (STEMI), complexity of percutaneous coronary intervention and coronary disease location. Bleeding risk is based on criteria established by the Academic Research Consortium.⁷

The preferred choice of P2Y₁₂ inhibitor when starting DAPT (with aspirin) is ticagrelor or prasugrel, rather than clopidogrel, due to the increased efficacy of these medicines.^8,9

Following completion of the recommended course of DAPT, people should be prescribed long-term single antiplatelet therapy. Switching to single antiplatelet therapy with a P2Y₁₂ inhibitor can reduce bleeding risk, compared with long-term DAPT, while offering similar protection against recurrent MI.¹⁰ P2Y₁₂ inhibitor monotherapy is preferred over aspirin as these medicines confer superior protection against MI and major cardiac events, with a similar risk of major bleeding.^10-12

Clopidogrel is currently the only P2Y₁₂ inhibitor available as single antiplatelet therapy on the Australian Pharmaceutical Benefits Scheme (PBS). While some evidence suggests that genotype-guided selection of P2Y₁₂ inhibitor therapy may offer an optimal balance between safety and efficacy, genotyping is not routinely available in Australia and further research is needed to determine its role.

Anticoagulation therapy in people with atrial fibrillation

In people with an ACS requiring anticoagulation for atrial fibrillation, direct oral anticoagulants (DOACs) are preferred over warfarin (due to a lower risk of bleeding), with the exception of people with rheumatic mitral stenosis or a mechanical heart valve.¹³

The 2025 guideline provides a strategy for people taking DOACs (rivaroxaban, dabigatran and apixaban) for atrial fibrillation to step down from combined DOAC and DAPT (triple therapy) to DOAC and single antiplatelet therapy, based on the person's ischaemic risk (Figure 2).

People at high ischaemic risk (with low bleeding risk) should continue DOAC plus DAPT (aspirin and clopidogrel preferred) for up to 1 month. This recommendation is based on results from the AUGUSTUS trial, which found that, in people taking an oral anticoagulant and a P2Y₁₂ inhibitor, continuing aspirin beyond 30 days increased bleeding risk without reducing ischaemic events.¹⁴

The guideline recommends that the DOAC and single antiplatelet therapy (clopidogrel preferred) continue for 6 to 12 months (depending on bleeding and ischaemic risks). Of note, lower bleeding rates are observed with a DOAC and clopidogrel compared with warfarin and clopidogrel.¹⁵

People prescribed triple therapy (anticoagulant plus DAPT) should also be prescribed a proton pump inhibitor to reduce the risk of gastrointestinal bleeding.⁶

Lipid-modifying therapy

The 2025 guideline offers a new recommended treatment target for low-density lipoprotein cholesterol (LDL‑C) of less than 1.4 mmol/L, with at least a 50% reduction from baseline following an ACS. This is a more stringent target than in the previous guideline and brings Australia in line with international guidance.¹⁶ The updated recommendation also acknowledges that people can gain further benefit from treating LDL‑C to the lowest attainable level.

People with an ACS should be initiated (or continued) on a high-potency statin (atorvastatin or rosuvastatin) at the highest tolerated dose as early as possible during their hospital admission, irrespective of baseline LDL‑C, unless contraindicated or completely statin-intolerant. Therapy should continue long term. If statin therapy is not tolerated or is not effective in reaching the LDL‑C target, ezetimibe may be added.

Addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor is recommended if LDL‑C remains elevated on oral therapies. PCSK9 inhibitors currently available in Australia are evolocumab and inclisiran. Both are listed on the PBS as a treatment for familial and non-familial hypercholesterolaemia (the latter in people with symptomatic atherosclerotic cardiovascular disease) and can be initiated by a GP in consultation with a specialist physician. These medicines are administered via subcutaneous injection; fortnightly to monthly for evolocumab, and 6-monthly for inclisiran (after initial loading doses at baseline and 3 months).¹⁷

Beta-blocker therapy

In people with an ACS and confirmed left ventricular systolic dysfunction, long-term use of a beta blocker with proven benefit in heart failure with reduced ejection fraction is recommended (specifically bisoprolol, carvedilol, metoprolol [controlled or extended release] or nebivolol). See the 2018 Australian heart failure prevention guidelines for further details including other recommended therapies.^18,19

However, for people with preserved ejection fraction post-ACS, recent evidence suggests that the benefits of beta-blocker therapy are limited. In a 2024 randomised clinical trial, over 5000 people post-MI with preserved ejection fraction were randomised to receive long-term beta-blocker therapy or no therapy.²⁰ For the primary composite endpoint of death from any cause or new MI, there was no significant difference in risk between the 2 groups (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.79 to 1.16, p=0.64). Therefore, the guideline makes a weak recommendation that healthcare professionals can consider not starting a beta blocker in people with preserved left ventricular function who have undergone coronary revascularisation and are otherwise receiving optimal medical therapy.

Renin–angiotensin antagonist therapies

Angiotensin converting enzyme (ACE) inhibitors (or angiotensin receptor blockers [ARBs] if ACE inhibitors are not tolerated) remain a cornerstone of post-ACS pharmacotherapy in the 2025 guideline.⁶ The guideline, however, makes 2 new recommendations regarding the use of other renin–angiotensin–aldosterone antagonist therapies:

• a strong recommendation for starting a mineralocorticoid receptor antagonist (e.g. eplerenone), in addition to an ACE inhibitor or ARB, in people with ACS, left ventricular ejection fraction less than or equal to 40% and heart failure with or without diabetes, because this drug class has been shown to reduce mortality and cardiovascular hospitalisations²¹
• a strong recommendation against starting an angiotensin receptor–neprilysin inhibitor (ARNI), as there is no clear benefit in people with reduced left ventricular ejection fraction after an ACS, and there is increased risk of adverse events.²²

Colchicine therapy

Colchicine is a well-established treatment for inflammatory conditions including gout and acute pericarditis.²³ Evidence previously suggested colchicine may be beneficial post-ACS by treating residual inflammation.²⁴ However, a more recent randomised controlled trial involving approximately 7000 people post-MI found no benefit from colchicine compared with placebo over a median follow-up of 3 years.²⁵ Given the mixed evidence, the ACS guideline makes a weak recommendation to consider initiating colchicine at a dose of 0.5 mg daily and continuing long term, unless contraindicated or not tolerated. Troublesome gastrointestinal adverse effects are common with colchicine.

GLP-1 analogues and SGLT2 inhibitors

The 2025 guideline acknowledges the emerging role of glucagon-like peptide-1 (GLP-1) analogues in secondary prevention of ACS, but does not make a formal recommendation for their use. In the landmark SELECT trial, around 17,000 adults with established cardiovascular disease and overweight or obesity (without diabetes) received either 2.4 mg subcutaneous semaglutide weekly or placebo. In the semaglutide group, there was a statistically significant reduction in the combined incidence of cardiovascular death, non-fatal MI and non-fatal stroke (HR 0.80; 95% CI 0.72 to 0.90).²⁶ At the time of writing, these medicines are not available via the PBS for any indication other than type 2 diabetes.

In the context of coexisting coronary heart disease and type 2 diabetes, GLP-1 analogues and sodium-glucose co-transporter 2 (SGLT2) inhibitors have cardioprotective effects that are independent of blood glucose levels. Both drug classes have been shown to reduce the risk of recurrent cardiovascular events and mortality, with SGLT2 inhibitors also showing beneficial effects for heart failure hospitalisation and in worsening renal disease, and GLP-1 analogues showing significant weight loss effects.^27-30 Although not formally covered in the guideline, as a reduction in recurrent ischaemic events has not been proven in the immediate post-ACS setting, these drugs should be considered by prescribers for people with type 2 diabetes and stable coronary heart disease.

 

Vaccination against respiratory pathogens

The 2025 guideline makes a consensus recommendation for vaccination against respiratory pathogens in people with ACS. Evidence shows that vaccination against influenza and other respiratory pathogens (e.g. respiratory syncytial virus, COVID-19 and pneumococcal disease) can reduce the risk of adverse outcomes in people with ACS or established cardiovascular disease.^31-33

 

Nonpharmacological secondary prevention

The 2025 guideline emphasises the ongoing critical role of nonpharmacological interventions for secondary prevention of ACS, in conjunction with pharmacological therapies (Box 1).⁶

 

Conclusion

Secondary prevention of ACS improves cardiovascular outcomes and reduces the risk of recurrent events and death. The 2025 Australian ACS guideline provides new and updated recommendations for secondary prevention. It emphasises the importance of combining pharmacotherapies with nonpharmacological interventions including cardiac rehabilitation and education about healthy behaviours; and ensuring adherence to long-term drug therapies.

This article was finalised on 12 December 2025.

Conflicts of interest: Jasmine Just is an employee of the Heart Foundation and was a member of the working group for the acute coronary syndrome guideline 2025. Jasmine Just, David Brieger, Alexandra (Sasha) Bennett and Tom Briffa all contributed to the authorship of the guideline. Tom Briffa has received research funding from Abbott Australasia.

This article is peer reviewed.

 

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