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

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You'd imagine that after a significant medical event like a heart attack, most people would want to do everything possible not to have another one. But over time, we do know that adherence to prevention strategies dwindles. And with the high risk of another event after an acute coronary syndrome, prevention really is key. And so today on the Australian Prescriber Podcast, we're going to cover part of the 2025 Australian Guideline on Acute Coronary Syndromes. We're going to focus on secondary prevention. We'll cover the recommendations and ways we as healthcare providers can improve the uptake and the maintenance of these measures with our patients. My guest is Professor David Brieger, the head of Department of Cardiology at Concord Hospital and a professor of cardiology at the University of Sydney. David was a co-chair of the guideline writing group. He, along with colleagues, have authored an article for Australian Prescriber, and it's great to have him here to discuss the recommendations. Thank you, David, so much for coming on the podcast today.

Thank you, Laura. It's an absolute pleasure.

Before we get into the nitty-gritty of anti-platelet drugs and other medications, can we take a step back and remind ourselves of why it's so important that we dedicate attention to comprehensive secondary prevention strategies?

I think what's known but not often thought about is that a lot of events following an acute coronary syndrome occur in the months after the event, and these can be very effectively prevented through secondary prevention therapies. Yet there is this tendency for our patients once they've had their event to regard themselves as being largely treated and often cured, and they tend to stop taking their medications. It's estimated that about 90% of patients are taking their guideline recommended medications at discharge, and that declines to just over 65% at 2 years. So the implications of this non-adherence is quite dramatic. It results in a number of preventable events. So we believe it's very important to prioritise post-discharge education and management to ensure these medications and other strategies continue.

And certainly when someone's had an acute event, you've got a captive and very motivated audience. And we definitely know in primary care and other healthcare providers who see people longitudinally, it's a great time to check, are these secondary prevention strategies still being maintained? And if not, why?

That's right.

It kind of segues into whose job is it to look after secondary prevention, what team members, what healthcare professionals should be listening to this article? Hope you are already, or if you're not, what colleagues should you send this link to?

Certainly the audience for this guideline was primarily medical professionals, but a lot of secondary prevention increasingly outside the hospitals falls on nursing staff, falls on allied health professionals, falls on those that offer secondary prevention rehabilitation services. But at the end of the day, it's generally the cardiologists in the hospital that are responsible with the initial prescription and the GPs that need to provide oversight and ongoing engagement with the patients post-discharge.

And hopefully in community medicine and general practice, we are still working with our allied health colleagues. We might not be as co-located as you might be in a hospital. One of the things that your article does mention in one of the really excellent pop-out boxes are all the secondary prevention strategies that are actually non-pharmacological. And so maybe we can just briefly list those before we deep dive into the pharmacological options, because I guess this is where we do involve the whole multidisciplinary team.

I mean, this has been an enormous focus of secondary prevention in recent times. There are a number of NHMRC [National Health and Medical Research Council] funded studies that are ongoing investigating ways of optimising this because we recognise it as being a limitation. So the box that you're referring to has a series of 5 points, which I'll briefly summarise now. The first is suggesting that all patients are referred to a multidisciplinary, ideally exercise-based, rehab programme following an ACS [acute coronary syndrome], if that's possible. The second important recommendation is that they are provided with advice and education on behavioural changes, such as healthy eating, regular activity, smoking cessation, limiting alcohol, and importantly, caring for their mental health. The third is a recognition that we need to think about strategies to optimise medication adherence, recognising the problems with adherence that we've described earlier, such as alerts, reminders, fixed-dose combination medications, which are easier for patients to take.

And this is proving to be quite a fruitful area of research in terms of optimising medication adherence. The fourth recommendation is to screen all people for depression and other mental health conditions, because that's something that's largely under-recognised. It became an enormous focus during COVID and has remained so, and this is a major driver of non-adherence. And finally, it's recommended that all patients know what to do should they have recurrence of their symptoms. So they should have a chest pain management plan, which includes the potential use of antianginal medications and guidance on when to seek urgent attention.

And many of these patients are coming through our general practice doors, our pharmacy doors. We do have opportunities to see them. And while a lot of our focus might be on the medications, it is a good opportunity to remember these really potent non-pharmacological strategies. Let's move on to medications. And look, antiplatelet medications are well established in secondary prevention, and the new guidelines have emphasised tailoring the duration of dual antiplatelets depending on patient groups, both their ischemic and their bleeding risk. Can you talk us through this new approach and how the recommendations have changed?

I think this is quite an interesting area. We recognise once we started putting drug eluting stents in that there was a risk of stent thrombosis, which was prevented by prolonged use of dual antiplatelet therapy. And what's happened in more recent times is evolution of stents, recognition of more potent lipid lowering therapies and the impact that that has on recurrent events, and we now understand that we probably don't need to be quite as aggressive with our dual antiplatelet therapies [as] we used to be. Whilst they're very effective at preventing thrombosis, a lot of these potent drugs we've been using are associated with bleeding risk, and that bleeding risk is recognised as having major adverse consequences and implications, particularly increasing mortality.

So sometimes if you're too aggressive with your antiplatelets, you're throwing a baby out with a bathwater causing a bleeding event that undoes all the good work you've done. So the default duration for a dual antiplatelet therapy following an ACS was traditionally 12 months and is now modified to being between 6 and 12 months. And then within that, there is a recognition that you tally your duration depending on the patient's individual bleeding and ischemic risk. So if a patient is at high bleeding risk, then we have a number of trials that show that it's quite safe to stop the second antiplatelet as early as one month after their coronary event if their bleeding risk is particularly high, but certainly at 3 months, it's often safe to stop the second antiplatelet if your bleeding risk is high. The other thing to recognise in that context is that traditionally when we stopped our second antiplatelet, you'll be aware that the 2 antiplatelets we recognise are aspirin and generally a potent ADP [adenosine diphosphate] receptor antagonist like Clopidogrel or Ticagrelor or less commonly now Prasugrel.

It's now been recognised that if you are continuing a single agent longer term, then Clopidogrel in particular is a more effective and comparably safe agent to aspirin. So that tends to be our recommendation once we have stopped our dual antiplatelets. Moving to the other side of the patient spectrum, the patients at high ischemic risk, but relatively low bleeding risk. These are patients that might have very complex stenting or proximal LAD [Left Anterior Descending artery] disease with large thrombus burdens that in the context of STEMI [ST-segment elevation myocardial infarction] concern us as cardiologists in the intermediate to longer term. For those patients, you may choose to continue your dual antiplatelet therapy for 12 months and sometimes for longer.

And you do put in a practise point for us prescribers that the PBS [Pharmaceutical Benefits Scheme] only lists Clopidogrel as a single antiplatelet agent, even though you could use Prasugrel or Ticagrelor [non-PBS as monotherapy].

Yes, and that is important. Clopidogrel, it's a good agent. There are some concerns or there were concerns in the past about Clopidogrel resistance and patients that didn't metabolise that drug into its active form because it's given as a pro-drug and then needs to be activated. And there is a small proportion of the population, about 4%, who don't actually activate the drug. But it hasn't yet proven possible to show that measuring metaboliser status in these patients is associated with improved prognosis. So we don't actually recommend that in the guideline. And it's also fair to say without getting too much into the weeds that aspirin also has a long history of resistance, as many of listeners I'm sure will be aware, and we haven't found that to be associated with adverse clinical events. So essentially at the moment, we tend to just prescribe these drugs without looking for resistance.

Another specific patient group that you focus on a lot in the article, people who've had an acute coronary syndrome, but also have AF [atrial fibrillation]. And so they need anticoagulation for the AF. And again, the new guideline does some risk stratification and we'll talk through it. Although I will remind our listeners, if you're a visual person, there's some actually really helpful clear decision trees and flow charts that you can follow in the article. So David, for AF and acute coronary syndromes, we're actually looking at a short period of time of triple therapy.

Yeah, so we recognised that dual antiplatelet therapy alone is not as effective as anticoagulation for preventing stroke in patients with AF. So initially before we had any randomised trial data to advisors, we would often put these patients who had AF and required anticoagulation, we would put them on what we call triple therapy, which was the combination of anticoagulation plus dual antiplatelets. That was associated in observational studies with a very, very large bleeding risk and bleeding penalty. We've subsequently had the evolution of the DOAC [direct-acting oral anticoagulant] drugs with which the audience will be very familiar. And we know that those drugs are far more easy to use than Warfarin and associated with an improved safety profile. And there have been a series of recent studies that have specifically taken the AF cohort for whom DOACs are generally recommended in general AF guidelines, and then studied the addition of antiplatelet therapy and looked at the impact on outcomes.

And the end result has been that we've arrived at what we regard as an optimal strategy, which consists of DOAC rather than warfarin, combined with a brief period of triple therapy of dual antiplatelet, that period ranges from one week to one month, depending on the patient's ischemic risk. And this is primarily driven by whether they've had high risk acute coronary syndrome or not. And if they have, then we may recommend it for a month. And if they haven't, then a week will be sufficient. And after that time, one of the antiplatelets is stopped and the best outcomes seem to occur when the antiplatelets you stop is aspirin. So, the longer-term therapy then becomes clopidogrel plus a DOAC, whichever one you select.

And then at the back end of that timeframe, which is generally between 6 to 12 months, again, recognising the penalty associated with bleeding. And the risk of bleeding is continuous. It remains as long as you're on dual therapy with anticoagulation plus an antiplatelet. At the end of that time period, we recommend that the antiplatelet be stopped, which again is quite a new strategy and not one that's widely recognised. And what you wind up with then is a patient with atrial fibrillation often with stents, but definitely coronary disease as well. But in a stable clinical scenario, they are managed with a single anticoagulant alone, just a DOAC, without a requirement for an antiplatelet.

That will be a shift for some of our listeners from previous practise.

Absolutely.

Of course, something that is not a shift at all is the fact that people for secondary prevention, if they weren't already on lipid modifying therapy, they definitely should be after their first acute coronary syndrome. But the new guidelines have an even tighter recommendation of an LDL [low-density lipoprotein] less than 1.4, which is now internationally recognised, and we've tightened our recommendation to meet international guidance. Is that right?

Yeah, this was a decision to which we gave a good deal of thought. And it stems from the fact that we've now got quite compelling data that shows that if you get your LDL down to a level of 1.4, you have a very potent impact on recurrent events. And in fact, in some studies of regression using intravascular imaging, you can see small amounts of regression when you get your levels down that low. And we're able to get there with the subcutaneous PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors with which we'll all be familiar and recognising that it's possible to achieve this and that if you do so, your outcomes are better. We've made a recommendation that we target an LDL as low as this. We've suggested that we do this with potent statins in hospital. That's not actually a new recommendation. That's one that's been recognised for some time. There's also the option if your high dose statin doesn't get you down to where you need to go, to add ezetimibe as the second line, a drug which is now available off authority, so it can be prescribed very efficiently without needing an authority prescription.

And if you're unable to get down to the levels that you like, you in some settings have the option of adding a PCSK9 inhibitor, although the threshold for addition is an LDL of 1.8, not 1.4. So the PBS hasn't quite kept up with the adding of a PCSK9 inhibitor in that setting. The key issues are that lower is better, potent statins should be initiated after an ACS, and there should be a low threshold for complementing that with Ezetimibe.

And David, we talked quite a lot around really clear guidance around the duration of time for antiplatelets. I'm actually quite curious, how quickly do you want this LDL to be under 1.4? How aggressively do you think we should be trying first potent statin and Ezetimibe, then asking a specialist colleague to help us with one of the new PCSK9 inhibitors?

There's really two reasons for being as aggressive as you can as early as you can. The first is when you've got the patient in the hospital or soon after their ACS event, you've got a captive audience and they're most likely to be compliant and most likely to be receptive to additional therapies. That I think is the strongest indication for starting early. In terms of objective data showing that very aggressive treatment very early on reduces events, there are small studies that suggest that that may happen, but in my view, I haven't seen larger, adequately powered studies that confirm the benefit of early therapies as dramatically as it might be suggested in another fora. But traditionally with lipid lowing therapies, we've seen the event curve start to separate at around about 6 months or so. But there is a hot inflammatory environment associated with an acute coronary syndrome that responds to more potent antithrombotic and more potent anti-inflammatory therapies.

And there is some argument that some of the lipid lowering therapies have anti-inflammatory effects as well. So there's a good theoretical reason as to why aggressive treatment earlier may be more effective than later, but I think the primary motivation and indication is just a pragmatic one to get people onto these therapies which you know are going to benefit them in the longer term.

I was also interested to read in the article that not everybody after an acute coronary syndrome is necessarily going to be prescribed or recommended a beta-blocker.

So this is an area that's been actively investigated over the last few years. We've suspected for quite a long period of time that the benefit of beta-blockers following MI was restricted to patients in whom there was left ventricular impairment. There is unequivocal evidence of the benefit of beta-blockers in patients with HFrEF [heart failure with reduced ejection fraction]. And that translated into the acute coronary syndrome arena also. We had recognised with the widespread availability of prompt reperfusion and also prompt access to the cath lab [catheterization laboratory]. We were often seeing patients who emerged from their acute coronary event with relatively well-preserved left ventricular function.

And it appeared that beta-blocker therapy didn't really impact favourably on their outcomes, really didn't have the effect that it had in the heart failure group. Those data were observational, but have now been confirmed by a number of prospective studies that have looked at patients following an ACS and pretty conclusively shown that in the absence of LV [left ventricular] dysfunction, there's no benefit of long-term beta-blocker therapy or even initiation of beta-blocker therapy in the initial post ACS phase. So these are new recommendations which have also been adopted internationally.

And it is still strongly recommended that an ACE [angiotensin-converting enzyme inhibitor] or an ARB [angiotensin II receptor blocker] are included post ACS, but you also include some new recommendations for specific groups of patients in these guidelines.

Well, ACE and the ARB have a long history of evidence of benefit and they're particularly beneficial in patients with diabetes or LV impairment or hypertension. The additional things that you allude to are a recognition that the MRAs, mineralocorticoid receptor antagonists like Eplerenone or Aldactone provide additional benefit beyond that provided by ACE or ARB in the AMI [acute myocardial infarction] setting, particularly in patients who have big infarcts, have a reduced ejection fraction and some evidence of heart failure. That's been known for some years and has been recommended, but that's been reinforced again in the guideline.

And the other related therapy that has been investigated in the post-AMI setting is the ARNI drugs, the angiotensin receptor-neprilysin inhibitor therapies, that have a firm place in the management of heart failure with reduced ejection fraction. But in the one study in which they were investigated in the post MI setting, they weren't associated with the benefit. So whilst there is a tendency to start these drugs in heart failure patients relatively early, we don't make the same recommendation in the post MI setting. Although once they've stabilised following their infarction, if they have LV impairment, they would benefit from these therapies as all patients with stable chronic heart failure do.

That's helpful to remember. And you did mention that immediately at the time of an acute coronary syndrome and afterwards, there is a really pro-inflammatory environment going along in these vessels. And colchicine, an old drug, has a good going anti-inflammatory effect. In your practise, how often are you reaching for colchicine as an addition?

I personally am not using it terribly often. The jury is still out. We've had some evidence of benefit through a series of trials over the last 10 years or so. Many of these trials have been led out of Australia, and we've been at the Vanguard of recommending these therapies, and certainly the anti-inflammatory benefit of these therapies are well known, but there are more recent data that call into question the evidence of benefit in the ACS setting. And as a result, in the guideline, we've only made a weak recommendation to consider initiating this therapy following an ACS. There are ongoing trials, both in Australia and elsewhere, focusing on patients with evidence of inflammation following their ACS, for example, to try and better tease out the subpopulation in whom the benefit is more apparent. But until those trials are awaited, you will find a variation in practise around the country.

Definitely one of those 'watch those spaces'. And thinking about some spaces that are being carefully looked at these days, the GLP-1s [glucagon-like peptide-1] and SGLT2s [sodium-glucose cotransporter-2], while they're not formally covered in the guidelines, many people who have had acute coronary syndrome may have comorbidities. It makes sense that actually they could get blood sugar benefits, cardiac benefits from these drugs. Are there select groups that you really think these drugs should be considered on after an event?

We should probably talk about them each individually. You're quite right. There's been an enormous amount of work done on these drugs and enormous amount of interest, and they've really revolutionised the obesity space and the heart failure space in recent times. The GLP-1s to start with are very, very effective for weight reduction, as we know. They're life-changing. And we as cardiologists have always recognised the burden that obesity places on people in their general life in terms of lifestyle, but also as a risk marker and contributor to acute coronary events. There has been a large 17,000 patient trial in patients with established coronary disease who were also overweight, but not diabetic, and it found a significant reduction in recurrent ischemic events, hard ischemic events, cardiovascular death, heart attack or stroke in patients who are randomised to the high dose of Ozempic. My understanding is that this recommendation is being considered by the PBS, and it may well be that the drug is funded for that group.

Now, these are not an acute coronary syndrome group, but many patients who recover from their ACS will fall into this cohort, and this is a therapy that will be available and I think will have a major impact on outcomes. The SGLT2s are the second class of agents that also was developed in the diabetes space. And among diabetics, SGLT2 inhibition has been associated with a reduction in cardiovascular events, but they've also leapt the bridge between diabetes and non-diabetes and found to be beneficial in patients with heart failure. So we do know that these drugs now form one of the core pillars of patients with heart failure. And in addition to that, they've shown effectiveness in patients with renal impairment. In terms of the ACS cohort, we haven't got evidence of benefit in starting these patients on these drugs in the ACS setting, so there is no objective trial yet that's shown benefit, but that may come. But at the moment, they're certainly recommended in patients with heart failure, but also in patients with type two diabetes who have evidence of foreign disease.

It is an evolving space. And as we are following up these patients over the long term, it's prudent for us to keep an eye on when these medications are listed on the PBS for certain indications, because currently we are in a tricky situation often as we find ourselves where something might be recommended, but not funded.

Yeah, that's true.

And finally, as we wrap up the recommendations in this article, and firmly back in the realm of general practise. I do want to remind everybody that everyone after having had their acute coronary event is recommended to be vaccinated against respiratory pathogens. It may seem completely left field for a patient saying, 'Why are you recommending this after your event?' But having a severe respiratory pathogen does put a lot of stress in the cardiovascular system, so it is excellent to vaccinate these people whenever you can see them.

Well, that's right. And more specifically, we recognise that vaccinating patients following an acute coronary event does improve their outcomes. It reduces the likelihood of them having further respiratory events, which in the peri ACS setting is associated with recurrent coronary events also. And interestingly, there is a moderate size study that suggests an impact on mortality following an ACS with vaccination. So in keeping with the principle that vaccination for respiratory pathogens is associated with the very favourable risk benefit ratio. And if it's not done in the hospital setting, it's often not done at all. There is a push to initiate vaccination as early as possible. I think that's an area that is underappreciated by both patients and also clinicians treating an ACS cohort and one that we've addressed in the guideline, and I expect will get more traction in the near future.

A bit of a call-out to all of the practitioners out there who are seeing people, if not at their immediate event, post-discharge, returning for their repeat scripts to really consider all of these strategies and not just advise and educate, but really assist them and think about what are these barriers to continuing prevention strategies that are probably recommended in the hospital. So I hope all of our listeners have got a lot out of our discussion today. I certainly have. Thanks very much, David, and to all the guideline authors and for putting together this article that summarises a very lengthy guideline into some salient points for us.

It's a pleasure, Laura. Thanks very much.

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The views of the hosts and the guests on this podcast are their own and may not represent Australian Prescriber or therapeutic guidelines. David Brieger contributed to the authorship of the Acute Coronary Syndrome Guideline 2025.

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