Aristeidis Katsanos

Hello everyone and welcome to our second session on secondary stroke prevention. In the previous webinar, we focused on identifying modifiable risk factors after stroke. Today we’re gonna take the next step. So we’re gonna be moving from what to target on how to actually reduce the risk in a meaningful and sustained way. I am delighted to be joined by an outstanding panel of experts, Dr’s Hanne Christensen, Joseph Kwan, and Jesse Dawson. Could I ask each one of you to briefly introduce yourself and just describe your main clinical or research focus in stroke care? Hanne?

Hanne Christensen

Yes, thank you very much Aristeidis. I am a vascular neurologist and I work as professor of neurology with the University of Copenhagen, and I work clinically as stroke consultant at Bispebjerg hospital in Copenhagen. And my interests are a bit too broad because it’s basically clinical stroke research and implementation.

Joseph Kwan

My name’s Jo Kwan, I work as a stroke physician at Charing Cross Hospital in London. My background is in general internal medicine and gerontology. My academic work is done at Imperial College London and I’m a senior lecturer there. I have a quite a diverse academic research portfolio, including acute stroke treatments and post-stroke complications. In the last decade or so I’ve veered into lifestyle medicine and lipid lowering. So my current focus is now stroke prevention, especially with lifestyle changes and lipid lowering. Thank you.

Jesse Dawson

I’m Jesse Dawson. I’m a professor of stroke medicine at the University of Glasgow in Scotland and work clinically as a stroke consultant in NHS Greater Glasgow and Clyde. And my background is a little different. I’m not actually a neurologist by training, although I I trained as a stroke specialist. My background was really in clinical pharmacology and in cardiovascular risk factor management. So one of the key areas of interest I had as a trainee and as an early consultant was actually in blood pressure and ran a large hypertension clinic in the west of Scotland. So very motivated to try and improve the way that we can we can prevent second strokes and recurrent strokes.

Aristeidis Katsanos

Thank you so much for all being here and sharing your expertise. I’m so glad to hear all this diversity in expertise. We’re gonna have a wonderful discussion. So let’s get started with the medical interventions that we actually use in our everyday clinical practice. We have stroke evidence supporting a wide range of pharmacological therapies for stroke prevention. One of the most important pillars is anti-thrombotic treatment. So we have antiplatelets, anticoagulants. And let’s start with that, Hanne. So can you give us an overview of the blood thinners we’re using for stroke prevention?

Hanne Christensen

Certainly, thank you. I think when you have a stroke patient and you need to decide how to continue with the anti-thrombotics, then the first thing you need to figure out is whether this is a cardioembolic or non-cardioembolic stroke. Of course, you may not know that it’s cardioembolic before having the Holter results, so you must go via what you know at the time, whether it’s cardioembolic or not cardioembolic. If it is cardioembolic, then it’s mainly about atrial fibrillation but there’s also a number of high-risk structural cardiac conditions that could lead to cardioembolic stroke, including more thrombi, mechanical waves, valves, et cetera. But the vast majority of these patients will have atrial fibrillation.

For anticoagulants, we have the DOACs, the direct oral anticoagulants, and there are three Factor Xa inhibitors, one direct thrombin inhibitor. And overall I would say they are all excellent drugs, very comparable as to benefits and harms. They have the advantage of fixed dosing. And for the majority of patients, the selection of the actual drug can be made based on priors and number of daily doses. And the dosing should be done as recommended by the manufacturer and will depend on things like age, weight, kidney function. But always look it up because there are four of them and nobody can remember everything.

So when can you start it off, start the OACs, after an ischemic stroke? You can start it within 48 hours after a minor or moderate stroke. Or on day six or seven after a major stroke. And you must be aware that in the older days we initiated the OAC pretty much later but based on newer data, there is probably, or there is, based on the ELAN study at least, a slight advantage as to the reduction of early events by initiating as early as that.

There is also warfarin which has been used for many many years and I think it’s important that we are aware that if the patient is kept at 70% of the time in therapeutic interval, then it is actually rather comparable as to both benefits and harms as to DOACs. And that can be achieved through self-monitored VKA, but overall this is extremely difficult, cumbersome, and takes a lot of resources to achieve while most clinicians prefer using DOACs. And also because of all these blood tests, because of course the dosing is based on the INR. But there are specific conditions like mechanical valves and antiphospholipid syndrome that must have VKA.

If we go to the non-cardioembolic stroke, which for most patients will simply mean they don’t have AFib. You have to look at short-term versus and long-term because these are two different issues. And I’m following very closely the ESO guidelines in what I’m saying and not just all guidelines, and I just want to recognise that Jesse Dawson was actually first author of both of these ESO guidelines. And as to the short-term when we’re talking about dual antiplatelet treatments, this is really about the balance of benefits and harms. That is the double, dual antiplatelets will inevitably reduce the risk of a thrombus but it will also increase the risk of a bleeding. Therefore the question is to reach the sweet spot of timing and stroke severity. So the recommendations are based on trials but pathophysiologically I think we can say that this is really based on the timing, reaching the sweet spot between thrombus and bleeding, with the risks going down in the days and weeks after the event. We end up having a recommendation, which is strong from ESO, that in minor stroke, which is very minor NIH below or at three, or high-risk TIA, dual antiplatelets with ASA and clopidogrel for 21 days, is recommended if initiated within 24 hours of onset. There is also a less strong recommendation for ticagrelor and ASA to be used in mild to moderate stroke, that is going up to five NIH and high-risk TIA, for 30 days but it must also be initiated within 24 hours. I think that the clopidogrel and ASA option is what is really mostly used.

And then long-term will be from 21 days and onwards, is monotherapy, anti-platelet monotherapy. In the ESO recommendation, we do not say that this should be aspirin or this should be clopidogrel. It is a monotherapy of anti-platelet therapy that is recommended, and this is a strong recommendation.I just also want to mention that there is also the option of aspirin plus dipyridamole, this is of course two drugs but dipyridamole itself does not increase the bleeding risk and it is well tested. It is also an option for some patients. It is more cumbersome, it’s more expensive in most countries, but it is certainly an option. And ESO also recommends directly against long-term use of antiplatelets due to the risk of harms, but longer-term treatment can be relevant in severe intracranial atherosclerosis as the main issue. There is also the option in specific patients after specific consideration, who have generalized atherosclerotic conditions including peripheral atherosclerosis, also ischemic heart disease and prior stroke and lesions in the carotid, we mainly use it in the patients that keep having strokes – to use ASA and low-dose rivaroxaban based on the COMPASS trial.

So these are basically the recommendations and the options. So what to do? Make the first work-up of the patient, find out is it cardioembolic or non-cardioembolic. Ensure that in the mild strokes, minor strokes and high-risk TIAs that you can actually start the treatment within 24 hours so that the patient has the option of having dual antiplatelet treatment. And then ensure that the ASA is stopped after 21 days, at least in Denmark, continuing aspirin for too long is one of the most common pharmacological accidents that happens and this does actually and significantly increase bleeding risk if stopping is forgotten. And often patients may feel that if this is good, it’s good to continue. So a lot of intention on that. We actually hand out tablets for three weeks to avoid this issue. And then ensure that patients are well aware that they should continue the monotherapy of antiplatelets life-long.

Aristeidis Katsanos

Thank you so much Hanne for presenting this wealth of evidence, summarizing very nicely into an algorithmic approach and also sharing your clinical experience. So we’re gonna move from the anti-thrombotics to another pillar which is the lipidemia management. So Jo, I’m coming to you and I would like to ask you what are the agents which we that we use and which targets should we aim for? And Hanne mentioned a lot about you know stroke subtyping, presumed etiology and timing of starting antithombotics. Is this something that we take into account when we start the agents to reduce the LDL or triglycerides? What are your thoughts on that?

Joseph Kwan

Yeah, thanks so much. It’s a great question. It’s taken quite a few years for LDL to be established as a major risk factor for ischemic stroke. Unlike acute MI or ischemic heart disease, their relationship is very, very solid, even four or five decades ago. But research in the last couple of decades have really consolidated the place of LDL lowering in prevention of acute ischemic stroke. So for example, we have the SPARCL study that, using atorvastatin at 18 milligram for patients who’ve had a stroke, the number needs to treat to prevent one stroke or TIA was only eleven. And the number needed to treat to prevent one major adverse cardiovascular event was only five. So when you use statins, high-dose, high intensity statins to treat a stroke patient, you’re not only reducing the risk of another stroke, you’re reducing the risk of ischemic heart disease, peripheral artery disease, aortic aneurysms, etc. So it is a very, very worthwhile treatment. For every millimole reduction in LDL, it equates to twenty percent relative risk reduction in stroke risk. So it is now a very important part of the armour of stroke prevention strategy.

In terms of targets, that’s a really good question. It’s really interesting how different countries have different targets. So if we follow, the first one I want to talk about is the European Atherosclerotic Society, or the European Society for Cardiology, the ESC, guidance, because that is the one that most European countries follow. In that they had an update in 2025 and they tend to go harder. They go quicker and harder with the statin and lipid lowering targets. So even with one event, and it doesn’t matter whether it’s cardiac event or cerebrovascular event, their target is already down to 1.4, even just with one event. With polyvascular events, so for example, someone who’s had a TIA or stroke and ischemic heart disease or acute coronary syndrome, with two things together, they go straight for a target of one. LDL target of one or below. So when you have a recurrent event, again the target is below one. So they go hard and strong. In the UK, we’re slightly different. So our national clinical guideline, the target is 1.8, which is the target they use for the treat-to-target trial. But in the NICE, which is the National Institute of Clinical Excellence that we have in the UK, they take into account the cost-effectiveness, and they have an LDL target of two or below. So we have this kind of slight discrepancy between guidelines and between countries. But the question is, is it safe to go well below that? And towards one, which is quite often found nowadays. And it’s really nice to see data coming out recently to show that LDL of one or below is not only safe, but also had clinical benefits.

So the general approach to lipid lowering after a stroke is strike early, strike hard. The first line that we use and most people use is hydostatin. So some people use atorvastatin, for example, in the UK as first line. Some people use rosuvastatin as their first line. And then we start adding other ones. The oral agents to add are ezetimibe and bempedoic acid. They’re the two main oral agents. There are combined tablets of ezetimibe and bempedoic acid in the UK. That is called Nustendi. That is an approved treatment. We also have the injectables, and they are the PCSK9 target injectables. One is the monoclonal antibodies, and there are two on the market. One is called evolocumab, one is called alirocumab. The other one is the small interfering RNA, and that is called inclisiran. And they differ mainly in the frequency of injections. So for example, inclisiran is twice a year, whereas the MABS are usually once a month. So the combination, if you use the EAS guideline, which combination you use depends on your baseline LDL at the time of the event and how much you want to reduce your LDL by. So as a rule of thumb, if you use high-intensity statin, such as atorvastatin, 80 milligram, you’re expecting about 50% LDL reduction. If you add every oral agent you add, the rule of thumb is you add another 10% reduction. So it goes 50%, 60 and then 70% if you have all three oral agents. The injectables are more potent. Each one reduces by about 50%. If you add it onto a statin, and the oral agents, you can reach above 75% or even 80% reduction from baseline. So that is how we target which oral and injectable agents to use, depending on how much you want to reduce it by.

Triglyceride, you mentioned, it’s another emerging really important risk factor. How do we know someone has high triglyceride or not? That is determined by a fasting triglyceride of 1.7 or a non-fasting triglyceride of above two. That is what we mean by high triglyceride. Interestingly enough, triglyceride is mainly from a high-fat diet or insulin resistance as part of a metabolic syndrome. So the first line of treatment is to change their lifestyle and diet. And then afterwards, if they’re still high, there are medications such as the fibrates, such as fenofibrates, but also there’s a new medication called icosapent ethyl. And that is a highly purified form of omega-3 EPA. But importantly, only icosapent trial has been shown to reduce mace outcomes.

Coming to the last thing, which is to do with stroke etiology. Although LDL is a predictor for all stroke subtypes, including with cardioembolic strokes, but all the trials show that statin-based treatments are only effective for those strokes caused by atherosclerotic disease. If you have a stroke caused by dissection and some genetic disorder, statin has no proven benefit in those patients and there is no, then if they have a high LDL at that point, that is regarded as a primary prevention. We use scores like Q risk three or score two in Europe to predict whether we use a statin or not. So that’s a summary of the lipid lowering aspects.

Aristeidis Katsanos

Thank you so much, Jo, for this absolutely stunning and great overview. So now let’s talk about blood pressure management. So I did hear that Jo mentioned that when you’re dealing with lipids, you strike early, you strike hard. Is it the approach that we should be taking in the management of hypertension, Jesse? What is your approach in treating high blood pressure?

Jesse Dawson

Yeah, thank you very much. So I think we need to tease out some of the issues around acute management of blood pressure in the context of acute endovascular therapy and thrombolytic therapy, for example, and prevention of stroke thereafter. And I’m not going to focus on the acute treatments, but really just deal with when we think about starting preventative treatments for blood pressure and why. And although, it’s certainly nice to hear about the changes in lipid management. The blood pressure field has been less dynamic, I think, before, but that doesn’t you know, in recent years, but that doesn’t mean it doesn’t remain probably the most important risk factor for stroke in terms of population attributable risk. And we know that blood pressure level has a log-linear relationship with risk of stroke, so a 20 over 10 increase in blood pressure is associated with a doubling of the risk of stroke, and that’s also the case for risk of recurrence. So it’s a hugely, hugely important risk factor. And we know that lowering the blood pressure works. When we performed the meta-analysis for the ESO secondary prevention guideline of blood pressure reduction, there was roughly a 20% reduction in the odds, in the risk of recurrent stroke in people with ischemic stroke when blood pressure was lowered. So at the most simple level, we know that lowering the blood pressure is a hugely effective treatment. And we also know that the benefit is greater in intracerebral haemorrhage in terms of the risk reduction that it affords. So the obvious question is: should we use blood pressure-lowering drugs? Of course we should.

There becomes a much more difficult question, an important question around the targets that we should aim for. And this has in the past been complex where there were different targets for stroke, for myocardial infarction, for CKD, for diabetes, for example. But there has been a general coalescence around a more intensive approach to more blood pressure reduction. And indeed, if you look at the stroke-specific data, you see that across three studies that we looked at when we did the secondary prevention guideline, SPS3, PAST-BP and the RESPECT study, comparing a more aggressive approach to aiming for a blood pressure of less than 130 over 80 was associated with a significant reduction in the risk of recurrent vascular events compared to a target of 140 over 90. So intensive control in people with stroke is better. And again, that risk was particularly, or that benefit rather, was particularly great in people with intercerebral hemorrhage, or sorry with regard to hemorrhage as an outcome, where the risk of a hemorrhage was almost halved. And that was in people with an ischemic stroke. So it’s a hugely effective approach to lower the blood pressure. And generally speaking, we should be aggressive aiming for a target of of 130 over 80. So I think that’s our starting point when we think about blood pressure is aim for a target of 130 over 80 unless there is a specific reason not to. And it is important to note that there are concerns in some groups of patients about more intensive blood pressure reduction. And I think the obvious one to highlight would be carotid disease. If you look at data from the endarterectomy studies such as NASCET and ECST, there does appear to be a relationship between a higher stroke risk and a lower blood pressure in those with bilateral severe disease, but that’s a small group of patients that we see.
And I think perhaps the more clinically important nuance that we have to consider is age. As we’ll all know, the average age of patients in a clinical trial is far less than the average age of the patients that we treat, and they tend to be much cleaner populations in terms of frailty and comorbidities. And it’s certainly true that we do not have good data on how low we should go with blood pressure in a frail population. And again, some studies have shown that intensive treatment can be associated with adverse outcomes in people who are extremely frail. So we do need to have that nuance in our mind. And also we know that the treatment effect of lowering the blood pressure in an older, frail person is less in terms of the number needed to treat for important outcomes such as mortality, because of those competing risks of other outcomes.
And another subpopulation of interest is people with renal disease. And we think about that, I think, for two reasons. One is many of our people with stroke that we manage will have renal disease, and lowering the blood pressure is important to reduce the risk of renal disease progression and other cardiovascular outcomes. But we did see in subanalysis of the SPS3 trial and also in post-hoc analysis of the SPRINT trial that intensive blood pressure reduction has been associated with a reduction in EGFR and some adverse renal events, but that was greatly outweighed by cardiovascular and all-cause mortality benefits.

So again, just to summarize that so far, obviously we should lower the blood pressure. In principle we should be more aggressive, we should be aiming for 130 over 80 millimeters of mercury as our starting point, and then taking a step back in saying are there any high-risk features that would make that blood pressure target inappropriate for this patient, such as bilateral carotid disease, such as advanced frailty at advanced age, and risk of renal complications.

And then the more difficult questions and where I think it does get a bit more fun is well, how do I do it, and what do I use? My approach is certainly just to follow the British Hypertension Society and the NICE UK guidance for blood pressure lowering, because it has a very simple framework of ABC and then fourth-line treatments. So you start with either an ACE inhibitor or an angiotensin receptor blocker or a calcium channel blocker or a thiazide diuretic, more appropriate for stroke patients to consider thiazides as a first-line treatment, dependent on age, dependent on other factors such as comorbidities. So we start on one of those drugs dependent on which is most suitable, and guidance often suggests to use a thiazide or calcium channel blocker in older patients, above the age of 55 or ACE inhibitors in lower patients where they may have a high renin state underpinning their hypertension. And then if you need a second drug, you pick one from the opposite side. So you would add in an ACE inhibitor to the thiazide or you’d add a thiazide into the ACE inhibitor. And if you need to move to third-line therapy, you could use those three groups together, an ACE inhibitor or angiotensin receptor blocker alongside a calcium channel blocker and a thiazide. And then we have fourth-line agents and the choices of that it becomes more complex, but options might be things like spironolactone, alpha blockers or beta blockers, dependent on what the potassium levels are, for example, and dependent on whether there are other comorbidities.

So that’s quite a nice simple framework to follow. But one of the questions that I think is of more contemporary interest is should you start with just one drug or should you start with two drugs? And again that there’s rationale for starting with two drugs as opposed to one. One is there’s some evidence that two low doses of one medication is as efficacious and associated with fewer side effects and is easier generally to use in terms of not having to have multiple dose titration steps for a single therapy. There’s no definitive evidence that using two drugs is better than one in in terms of outcomes, but it was interesting to see just a few weeks ago at ESOC, and this is in the intracerebral haemorrhage space, the results of TRIDENT that showed that using a polypool of three drugs was associated with a significant reduction in events thereafter. So I think using multiple therapies early after stroke will become an increasing question of interest. And certainly I’m beginning personally to move in that direction. Particularly, for example, if somebody’s blood pressure is 172 over 90. Starting an ACE inhibitor at a dose of ramipril 2.5 BD or perindopril 4 milligrams is not going to achieve the required reduction to get that patient down to 130 over 80 in all probability. So perhaps starting them on a dose of amlodipine at five milligrams and a dose of an ACE inhibitor, a starting dose of that will be more efficacious and make it easier for the GP to take on subsequent dose titrations by just doubling up the perindopril, doubling up the amlodipine. You might actually make the whole landscape a lot easier for the future management of the patient. But I’d be very interested to hear what agents other people use, because I don’t think this is an evidence-based area which agents we select after stroke, with the exception of the PROGRESS trial obviously showed us that using perindopril and indapamide in combination was highly efficacious. But which one you pick first and whether these are just class effects is an area of debate, I think.

Aristeidis Katsanos

Indeed, Jesse, I would also like to hear what other people are doing. I’ll have to confess that I’m still doing the old school approach, starting one agent and going up slowly. And the reason I’m doing that is because that’s what how I was trained, right? So but I would like to hear you know, Jo and and Hanne. What is your practice regarding agents and if you’re using if you’re starting with a combination or a single a blood pressure regime. So Jo, do you want to start with your practice?

Joseph Kwan

Yeah, it’s very personalized, isn’t it? It’s, as you say, it depends on so many things. So if they already have swollen ankles and they’re, you know they have postural blood pressure drop, then you know that might determine which agents you use. I mean, thanks, Jesse. I mean that’s a really nice summary and in my head I was thinking what about this group? What about this group? You know, older people with significant postural hypotension, recurrent falls, people with diabetic renal disease, you know, who who need renal protection, for example. So I mean I tend to start with a calcium channel blocker first if it’s rather mild. Like Jesse, I’m starting to do two agents quite often combining an ACE inhibition with a calcium antagonist or a thiazide with a calcium antagonist. So, yeah, it’s definitely a moving field. In the UK we don’t tend to have many combined tablets, whereas in the US and maybe in Europe they have more kind of combined agents, which patients find it easier to take, don’t they?

Aristeidis Katsanos

Thank you so much, Jo. And Hanne, what is the experience?

Hanne Christensen

Well actually we’re doing pretty much as Jesse said. And it’s also because we have a close collaboration with the GP so we see them once perhaps twice, and then they are returned to the GPs for blood pressure control. And usually that’s the way we go because it’s fast, efficient and patients do not complain too much.

Aristeidis Katsanos

As nicely presented by all of you, we’re very fortunate that we have a plethora of effective evidence-based interventions and you nicely outlined them all in your discussion. But unfortunately we still see big gaps between the evidence and real-world implementation. So Hanne, I would like to ask you to share your experience and and also your involvement with international stroke organizations on how we can actually make sure that we deliver intensive secondary stroke prevention strategies to our patients. We detect and treat post-stroke complications, but at the same time we increase patient self-empowerment. So what is your experience and what is the pathway we are taking and what is the pathway we should be taking?

Hanne Christensen

Well this is a difficult horizon but what we are all working in every day. But we have to be aware that at the moment about one in five strokes in Europe is actually a recurrent stroke, so there is something to work with. Of course, we all know that whatever we do it will not be zero, but one in five is probably too much. And if we look at the organisations over the European countries, very very few countries actually provide comprehensive and systematic follow-up, or even any kind of follow-up after stroke. That is in contrast to what is offered to people with cardiac conditions in most countries. And I think that is very much the basis of why we have these issues with the follow-up. And I think it is very interesting also based on the fact that patients after stroke do not only have the issue of secondary prevention to optimize treatment but also to ensure risk factor control or to those not treated pharmacologically, but there’s a lot of other issues and gaps.

Often they have mental and cognitive issues, resulting from the stroke. They have later drops in functioning and they may need to be returned to some kind of rehab. They have issues that may be very significant with participation, and they may be in family, that may be in society. They may develop pains, spasticity, that needs treatment or could at least benefit from treatment. There may be the carer situation, there may be the returning to work or not returning to work situation. So there is really a lot of issues that are pretty stroke-specific and that are often lost.
In the Action Plan for Stroke in Europe, our rather simple approach on what to do is to use the post-stroke checklist, which is actually a World Stroke Organisation tool, which is well validated. And also develop the nurse consultations and very practical because it includes defined actions for what to do if everything is not okay. And this post-stroke checklist includes all of the above. And that pretty much goes around what are the issues for most patients. Because what we see if we do not follow up on the pharmacological treatment is that patients may not have understood this is lifelong treatment. They might feel something uncomfortable and they may think this is a side effect. Often side effects are not real side effects like the muscle pain that is also very frequent in control groups in statin trials. There’s a lot of issues that need some kind of professional advice to support the patient in actually following up on the secondary prevention but also simply to have the blood pressure, the lipids controlled.

There are also other models of doing this. I mentioned the post-stroke checklist which is kind of a very simple thing that can be implemented in most countries. But there’s also an excellent case model is the Austrian one, the Stroke Card, which is kind of the deluxe version of the post-stroke checklist. This has also been tested in a very nice trial, also called Stroke Card Trial published in Lancet a few years ago. And this consists of a, during the admission patients are given access to certain tools including access to the MyStroke website which includes a lot of education and potential empowering elements. And then this is followed up at three months by a multi-disciplinary two- or three-hour consultation including re-assessment of stroke cause and follow up on secondary prevention as well as education, and carers are also included in this consultation. And the actual benefit from the Stroke Card Intervention Trial was rather impressive, and very impressive taking into account that this has not been implemented, to my knowledge, elsewhere other than Austria. That the intervention reduced the risk of major recurrent events by one third and it significantly both improved self-reported health-related quality of life and independence. So this may be a deluxe model but still if we look at giving access to a website and a bit of information during the admission, of course, on top of the other things that we do or should do, including lifestyle counselling, and one long consultation after three months, I think this will be cost-effective. I looked if I could find any calculations on it but I couldn’t. So I think that we need basically to set up and implement some kind of systems to follow up on patients after stroke. And I think the problem about just having one last consultation after three months, I think that may not be enough because follow-up after stroke might need some kind of long-term lifelong follow-up as to both the mentioned needs, but also to the secondary prevention. And I think that this could be looked at as some kind of opportunistic screening if the patient has been lost before. And at the moment there’s a lot of interest in health screening in Europe and I think this is really a wonderful business case for this.

So I think that we need to not only think about what drugs to give, exactly what advice to give, but also to ensure there’s a system and organisation that catches the patients and their carers and actually gives them the opportunity of receiving and using the given advice and also taking care of their other needs. So this is something that we really must discuss in the future.

Aristeidis Katsanos

This is very insightful Hanne, thank you for bringing up and highlighting the really high risk of stroke recurrence and also overlooked entities such as cognitive impairment in our patients. And as you said, that the risk doesn’t stop at three months but is a continuous, unfortunately for most individuals, a lifetime risk. So there is a growing interest in more specialized roles such as the stroke lipid specialist. Jo I would like to ask you if you can share your experience with this kind of model. And let us know whether it has improved patient outcomes or workflow in your center. And taking a step forward whether you think a model like that or similar models, can help tackle some of the challenges that were nicely presented by Hanne.

Joseph Kwan

Yeah, thanks very much. And it leads on very nicely actually from what Hanne was saying, which is the importance of empowering and educating the patient to know what they should or should not be doing, how they should or should not take medications and be compliant, etc. And there are certain aspects of stroke prevention which are very well done. So for example, anticoagulation for AF, blood pressure control. People know the routine pretty well, especially in the hyperacute stroke setting, in the hospital setting in the secondary care. And the primary care are also now very well versed in anticoagulating for AF and BP control.

One thing which I feel, and I think that is backed up by a lot of observational data is lipid lowering is not as closely monitored after the acute stroke event. It’s very common to find that when patients are discharged from the hyperacute stroke unit, there is this fire and forget approach. Starting, for example, atorvastatin 80 milligram and then discharge. No one tends to be taking responsibility to repeating the blood tests, escalating the medication dosage, maybe adding or changing the medication in order to reach the treatment target. So depending on which country you come from, maybe your primary care is much better developed. But in the UK, we are finding that no one is really taking responsibility in repeating the bloods, checking whether they are taking the statins and the other medications or titrating up towards the target. There is also, as you know, a lot of social media negative posts about statins. So that is what the patient and the family are seeing probably on a daily basis. On Instagram or Facebook telling them not to take statins or the very high risk of taking statins, which are not true, and then not telling them the real benefit of taking statins and lipid-lowering.

So we audited our pathway with a hundred patients coming through a hyperacute stroke unit. And we found that only 7% of our patients at follow-up reached LDL treatment target. 7% out of a hundred people. And the follow-up is at about six to eight weeks. So one thing that we did was to redesign our pathway and redesign our approach, which is to use allied health professionals, and not just relying on doctors changing practice or the primary care. So we employed a stroke lipid nurse to oversee the education of every new stroke patient coming through the hyperacute stroke unit, doing lifestyle education, explaining about what statins do. And not worry about the side effects too much, explaining about not just lipid lowering, but all the other important aspects of lifestyle education, such as giving up smoking and weight optimization. And then we added lipid clinic associated with our stroke follow-up clinic. So the nurse had his own clinic. And also I added a stroke lipid clinic, which is separate, especially to give the injectable therapy according to guideline. We also used a point-of-care machine to do a finger-prick test for lipid blood test. So we get the LDL, the total cholesterol and the triglyceride within one or two minutes of testing the point-of-care machine in the clinic. So we have instant feedback for the patient. Ah, look, the tablet you’re taking is really working well. Please carry on with it. And they feel this empowerment. Or look, you’re taking this medication and it’s not quite getting towards the lipid target. So we need to add another one. Because we are trying to get down to say 1.8 or 1.4. The patient feels much more involved in that because they see that finger-prick test result straight away. And the consultant or the medical person can make that immediate decision which is useful, rather than writing a letter to the GP that hopefully gets read in the next few weeks, and then hopefully something happens with a change of medication. What we found with this kind of pathway redesign using a new stroke lipid specialist nurse, our target, the patient reaching LDL target at follow-up went up tenfold to 72% at follow-up. That is actually comparable to some of the PCSK9 inhibitor trials, 70-odd % reaching LDL target. That is just by adding a nurse to improve the education, improve the pathway, and to add the point-of-care machine.

So I think what Hanne said was really, really good, which is to have a system, it’s a systematic way of making sure the patient knows what they’re doing. So, for example, even just getting a blood pressure machine at home, doing the blood pressure measurements at home, to know their numbers, to know their lipid numbers, know their BMI, know the the blood pressure, the fluctuations during the day. And the importance of that compliance with medication. Because as we know, a lot of patients we give them medication, we say, take it, receive it in three months. And we know that a lot of them their compliance drops off over time. So I think a systematic way of reminding them the importance of carrying on and reducing the risk of stroke, not just in the first few weeks, months, but years and years later, is really, really valuable. Yeah. Thank you.

Aristeidis Katsanos

And as you mentioned, in clinical practice stroke patients can be quite diverse. It’s not the patients we always see in clinical trials. So Jesse, I would like to ask you how you deal with competing risks, frailty, or complex comorbidities in your patients. would it be possible that you provide, a few clinical scenarios and how you deal with the targets, the agents, and how you approach those individuals.

Jesse Dawson

Yeah, absolutely. So it obviously is a huge area. And I think we have a number of different things when we think about personalized secondary stroke prevention to consider. One is that stroke is very heterogeneous and even within the subtypes of stroke, we then have very heterogeneous patients, as you say, and the very elderly and and frail are really, really, really important examples. And I think at the heart of this debate really or this question it is the risk of harm, isn’t it? You know, we know that an anti-thrombotic will have a similar effect in terms of thinning somebody’s blood and reducing the risk of a thrombus, but it may come with greater risk if somebody is very elderly and frail, for example, and have increased bleeding risk. And it’s the same with blood pressure reduction, as I mentioned before, and one of the key areas to consider is that the efficacy of some of these drugs when we talk about a 30% relative risk reduction. That might mean something very different in a patient who has a limited life expectancy because they’re old and frail and are likely to sadly die or succumb to other conditions such as dementia and neurodegenerative disorders that might not be receptive to the effects of blood pressure lowering, for example. And the same with lipid lowering. So I think we definitely need to take these things into account and consider the risks of the approaches that we’re considering for patients. So while we have the narrative that we want to be more aggressive and do more, and we’ve heard lots of good examples of why we might want to do that, be sure that we’re not putting specific groups of people at unnecessary risk and making sure that we treat them well.

So I think with the elderly and frail, it’s relatively straightforward. We need to be sensible. We need to think of the benefits for that individual person and interpret the clinical evidence in that light. And I think the other really important clinical scenario that I think we’re getting much better at in stroke is remember that people with stroke have other conditions too. You know, these are people with a high risk of recurrent vascular disease, often because they have comorbidities such as diabetes, comorbidities such as heart failure, atrial fibrillation, and ischemic heart disease. And sometimes those conditions might lead us to do slightly different things within the core pillars of secondary prevention that we routinely do. So, for example, if you have a patient who’s already on an antiplatelet, who comes in with a recurrent stroke, and who also has ischemic heart disease, we could begin to ask ourselves questions like, well, does the fact they have ischemic heart disease allow me, empower me to do more for this person in terms of prevention? So as Jo has very elegantly outlined, is there a case now, can I access more aggressive lipid-lowering treatments? Should I be going for an LDL of less than 1.4 as opposed to to 1.8 and thinking about add-on therapy? Or could I use the COMPASS regimen? Could I use an antiplatelet plus a low dose of an anticoagulant, for example, in a person who has ischemic heart disease and cerebrovascular disease as well.

And I think a really hot topic with regard to other patient groups are now people with diabetes and people with excess weight. You know, these are really high-risk individuals. And why should we leave a risk factor like poor metabolic health or excess weight on the table these days when we can perhaps access GLP-1 agonists or other approved therapies to improve that person’s, or reduce that person’s risk of having further events.
And I think just to highlight one final area which I think is really, really interesting and I think we don’t have the evidence base that we need, and that is what do we do when somebody comes in with a vascular event whilst taking what we think is good preventative therapy on the surface. So they’re on an antiplatelet, for example, they’re on clopidogrel and they come in and have another event. What should we do in that setting? And I’m not advocating there’s a particular answer with regard to switch or continue those sorts of things. But we should always use that as an opportunity to think about why might that treatment not be working for an individual person? You know, are they forgetting because of the drug regimen or is there a drug interaction that’s minimizing efficacy of one drug, or do they have some other untapped, unidentified risk factors such as paroxysmal atrial fibrillation that we could look for, screen for, and thereby treat them?

So again to surmise that, I think that the key patient groups to think about where things can be difficult and where we might need to personalize are the very elderly and frail, as you said. Remember the comorbidities and use them as a means to empower you to access better preventative treatments for your patients. And also just think about patients who come in with recurrent events despite being on what we think is good treatment and think really hard about whether there’s a reason why that regimen hasn’t had the effect that you would you would like it to have had.

Aristeidis Katsanos

Thank you so much, Jesse. All the points are excellent and thank you for sharing how you approach those very high-risk patient populations.

Aristeidis Katsanos

So the thing with those people is that they are not only at a very high risk of stroke and cardiovascular events, also medication compliance and adherence is a big challenge. And Hanne, I’d like to ask you how do you balance the intensity of the treatment, the tolerability of the treatment and adherence to it? Do you perceive that those goals are actually competitive, independent, or they are synergistic?

Hanne Christensen

Well basically I think this is a lot about communication. And I think it was very important what Jesse just said about reassessing why did this person have a recurrent stroke. And I think that we should always keep our minds open that we may not have reached the right result when working up patients. And I also think perhaps even more importantly that most of our patients they have signs of more than one stroke pathology. Often they have both small vessel disease and large vessel disease, or they have atrial fibrillation and atherosclerosis, and so this means that sometimes we may have to think a little bit pathophysiological which I otherwise do not like, to identify exactly how to cope with this patient.

But the thing about compliance, I think this is about information. It is about motivating patients beyond the fear of the acute event, because the fear will not last forever. Most people are optimistic, and most people will not be able to keep up the fear for more than two or three months. So you need to find your own motivation to go to somewhere where your risk is lower and they might even keep up their functioning, because that is what people fear whatsoever, everyone wants to be able to walk and talk. So I usually tell people about what the benefits will be, I usually talk about the risk reduction, I usually say, and this is based on some kind of evidence but of course not completely precise, that if they do exactly as they are told they will have about 80% reduction of the risk they would otherwise have for another stroke. And this bears the optimisation of saying, look you can do a lot of things. Because at least Danish people have kind of a feeling that stroke is something that happens and then it will continue happening no matter what you do, and this is what you have to deflate.

A lot of people are concerned about medication, side effects, but they are also very concerned about things which will inevitably happen. If you give people a diuretic, there will be a peeing problem and they might feel they have to stay indoors all morning because they have the diuretic in the morning. And you need to discuss these things otherwise they will stop taking the diuretic at least in these days when they have to do something. And the beta-blockers and the sexual functioning, especially in males, is another issue you need to discuss otherwise the patient will simply stop taking the medications. And you need to listen also to their impressions of what happens from side effects because if you don’t listen the patient will not feel that they’re taken seriously and that their complaints are actually evaluated, which is very very reasonable even if we do not have their complaints on our list. And then I think you need also to be willing to attack the overall medical chart, because polypharmacy is always a problem, and even though all three of us agree that the pills we are advertising at the moment are really really important, and that’s what I feel too, patients may end up with medical charts with 14 or 16 different medications. And that is never healthy because the patient may end up with something that is uncontrollable. So you must, as a stroke physician seeing these patients who usually have comorbidities, at least start looking at the medications and reducing the list, because that will often make patients much more willing to start another pill if you can take one out.

Then I think that these combined pills we use losartan and diuretic in one pill a lot in Denmark, and this really works very well because it’s simpler. Also the thing that we need to give two or three daily dosing is not always really needed, it may be optimal but having the medications may be better than having it at the optimal timing. So sometimes it’s about giving the medications once daily, all of them in one block in the morning, which is often possible even though statins are better in the evening but still in the SPARCL trial there was not a defined timing of the dosing. May be very helpful. And then always check for interactions because if you give the patient a side effect because of an interaction that you have not thought of, you will not be popular and you will not be listened to. And then there is also the interactions of natural medicines, at least in Denmark a lot of people are using so-called natural medicines like perikon for depression or John’s wort for sleeping. And these have a lot of interactions, also to the drugs that we are using a lot. So talk to the patients, listen to them, find out what they are using because the patients must live with their medications and they actually have the chance of forgetting every day.

Aristeidis Katsanos

Thank you so much, Hanne. These are all excellent points. And in fact, you did bring up two major things. One is communication with the patient and also is lifestyle changes, both very important but unfortunately overlooked. So Jo I would like to ask your strategies. What have you found to be the most effective in actually communicating to patients lifestyle changes, diet, exercise, smoking cessation? But more importantly making sure that those changes are going to be sustained for the patients and the individuals.

Joseph Kwan

Do you know what, in general, I don’t think doctors are very well prepared for discussing lifestyle and in terms of education support. Right from medical school, we’re not really taught about nutrition. We’re not taught well even during medical training, whether you are internal medicine or surgical training, there isn’t that comprehensive coverage of nutrition, physical activity, exercise, sleep, etc. And the WHO last year, the global stroke fact sheet said that up to 84% of strokes can be preventable by optimizing modifiable risk factors. Obviously it doesn’t always mean that we can really prevent 84% of strokes. But I think it just emphasizes the importance of lifestyle education and support for the patients, for that empowerment. Lifestyle medicine has now actually taken momentum to be a separate specialty altogether now. And for stroke patients, I think we are really talking about adopting a Mediterranean-style diet because it has polyphenols, it has antioxidants, it has plenty of fiber, and it promotes avoidance of ultra-processed food, high saturated fat, and also red meat. So that is kind of one of the pillars of lifestyle medicine. Another one is increasing your physical activity and exercise. And people often mix those two things together. Physical activity is what you do during your waking hours. So whether you are standing up or sitting down in the office, walking up and down the stairs in the house or just you know, cycling to work, for example. Whereas exercise is your defined period of higher-intensity physical activity with a clear goal of improving fitness. And then getting enough sleep, seven, eight hours a night of good quality, deep sleep, avoiding cigarettes and alcohol, managing your stress and staying socially connected. Those are your six pillars of lifestyle medicine that doctors often don’t have time or the knowledge to talk about during follow-up. And as Hanne already said about the WSO/WHO checklist, it has all you know have these things within it to talk about during your consultation. My mantra is it is everybody’s business. It is not just to do with the nurse, you know, go and talk to the patient, is not just to do with a physiotherapist. Can you talk about physical activity and exercise when you’re walking them? It is everybody’s business. And the doctor is quite often the person they look to with the highest respect to say, do this, don’t do that.

And I have six tips, if that’s okay, six tips of effective education for lifestyle. The first one is setting realistic goals rather than saying, cut out all the cigarettes and cut out all your alcohol, or you know, reduce your weight by, I don’t know, 10 kilogram. You know, we have to set more realistic goals. And you have to move towards those goals in a stable, steady way. Another one is involving their families and friends. Because by doing it together in a household, it is much easier to give up, for example, high saturated fats and ultra-processed food when it’s not, just not in the house to eat. You can’t see it in the cupboard. Don’t buy it for the whole family. So involving your family and friends in these lifestyle changes. Another one is reading your food labels. Always read your food labels. The amount of salt, the amount of saturated fat, the amount of sugar that you take in those foods. And deconstruct the food if you pick something up to buy. You just deconstruct that and say, is it what I’m putting in my mouth good for me or not? What is it that’s doing for me? And then another one is making it fun. You make it fun for the lifestyle changes. So trying new recipes, going dancing and ice skating for your exercise is much more fun than, you know, burning ninety minutes in a gym. Making it a routine. So for example, I tell my patients, just after each meal, go for a walk for twenty minutes. Then in a day you’ve walked for an hour, and that probably equates to about ten thousand steps a day, making a routine and making it a daily thing. And then lastly, to keep track on progress. There is now more and more apps and AI that is letting you keep track on your steps, on your percent fat, on your muscle mass, especially if you use those scales that you can get, probably very cheap nowadays, you can get one on online for about thirty pounds, about thirty Euros to these scales that give you the percentage fat and muscle mass rather than just your weight or your BMI. Lastly, I think it’s really interesting the move towards GLP-1 that Jesse talked about. You know optimizing your weight. It’s so important now. And people reach for that easy option of injecting themselves. I give a bit of a word of caution to my patients about very rapid weight loss, because afterwards there is some evidence coming out now that you put it back on quite quickly when you stop the injection. But also another thing is, when you lose weight, about thirty to forty percent of that weight is lean muscle mass. So you’re not just losing weight, you’re losing proper lean muscle that you use to run and to walk. ⁓ So, you know, when you use GLP-1, you have to pair it with resistance exercise and really focus on the amount of protein that you eat. Probably at least 1.2 gram per kilogram body weight per day, in order not to lose all that muscle mass. And my aim for them is to get fitter, not just get thinner. When you get fitter, physically fitter, you automatically optimize your weight, but it’s also good for your mood and your psychology as well.

Aristeidis Katsanos

Thank you so much, Jo, for summarizing all the important aspects of lifestyle changes and also sharing your tips on how we can communicate better with our patients and achieve the goals for our patients again. So as we’re reaching to the end of this webinar, Jesse, I would like to kindly ask you to summarize the three most important takeaway messages for our audience.

Jesse Dawson

Yeah, thank you very much. Now I’m gonna take a liberty here and I’m gonna give you four because Jo spoke so passionately there about lifestyle. So I’m gonna come back to that, which I think is great and really important. So I think my three takeaway messages would be number one, I think be appropriately aggressive. So aim for the targets. The targets exist for a reason and if somebody isn’t hitting those targets, act. But remember, and this is number two, that we do need to be specific and personalized. We need to consider the whole patient, think about their comorbidities, think about frailty and other things. And the third one would be that we need to all think about our structures to ensure adherence to the medications and follow up with targets and take some ownership of what happens in the longer term with our patients and with control of their cardiovascular risk factors. So they were my three. But I think it is worth mentioning after what you’ve heard about lifestyle, you know, a fourth one. Don’t forget about lifestyle measures. Don’t forget about giving people access to smoking cessation. You know, simple things that might just make a difference. They won’t make a difference to everybody, but even if you do it ten times and one person starts the journey to stop smoking, it could be tremendously impactful.

Aristeidis Katsanos

Thank you, Jesse, thank you, Hanne, and thank you, Jo. In today’s discussion, experts have highlighted that secondary stroke prevention is not just about prescribing the right medications. It’s more about integration, how we combine evidence-based therapies, lifestyle support, personalized care and multidisciplinary collaboration. Thanks again to our panelists for this insightful discussion and thank you all for joining us.

Aristeidis Katsanos: Research Grants from HSFC, CIHR, Brain Canada, HHS, HAHSO; Consulting fees for Diamedica Therapeutic Inc and Bayer Inc.

Hanne Christensen: Speaker’s Honoraria from Bayer.

Joseph Kwan: Honoraria from Boehringer-Ingelheim, Bayer and Novartis.

Jesse Dawson: Advisory Board for Bayer; Consultancy Fees from BMS and Janssen.