 Welcome to Texas Heart Institute Educational Programs on Innovative Technologies and Techniques. The purpose of these presentations is to inform and educate the general public as well as physicians and medical personnel on the latest advances in cardiovascular medicine. I'm your host. My name is Vanmer Kraser. I'm an interventional cardiologist at Texas Heart Institute and Baylor CHI Medical Center. Our guest today is Dr. Anne Abbott. She's a neurologist and she's an associate professor at Central Clinical School in Monash University in Melbourne, Australia. Welcome to Texas Heart Institute, Dr. Abbott. Thank you, Dr. Kraser. So the topic today of our discussion and conversation is treatment of carotid stenosis and differences between men and women. Good. Now, I would like to ask you, Dr. Abbott, can you explain to the participants of this program what is the fact-cats? Because if not the founder, one of the essential individuals that made this happen. For those that do not know, this organization is very successful in flourishing and expanding and it has a very meaningful purpose. So can you talk a little bit about it? Well, thank you very much for bringing this topic up. Fact-Cats stands for faculty advocating collaborative and thoughtful carotid artery treatments. And this group started with, well, two people really, was myself and Frank Vieth, who's a vascular surgeon from New York. And we got together in 2011 and we were quite concerned about pressure to widen reimbursement indications for carotid artery stenting to people at average surgical risk, so symptomatic and asymptomatic people. We were concerned because we felt that the randomized trials had been misinterpreted because we felt the evidence showed that stenting is actually more dangerous than surgery. And guidelines were coming out, advocating for more carotid stenting, which we didn't agree with. So we started a campaign and we rallied 41 opinion leaders from around the world and we wrote, we published an evidence review and advised to US Medicare for them not to expand stenting reimbursement indications. They didn't. They didn't because they saw the evidence that really there's no current indication for any carotid procedure because of changes in advancements in medical treatment. That's simply lifestyle factors and medication. And also they saw that stenting was more dangerous. So from there we also published another evidence review 12 months later and endorsed their decision. We had 51 opinion leaders at that stage who had come together and these people formed the first fact cats. From there we've always communicated by joint email so we can share publications, we can debate fact versus fiction and we can also talk about our own cases if we're having trouble with a particular case. Someone can just put that on our emails and sort of de-identified, but immediately you might get half a dozen responses from anywhere around the world, surgeons, medical specialists helping you with your treatment decisions. So we've grown to over 300 members now and we have several purposes really and it's to improve academic standards, education and also we're still an action group. So if the need happened again we could rally and lobby for certain things to happen. So I understand your point of view and the purpose of fact cat that you want to bring the truth to life as far as publications are concerned and also analyze critically randomized and non-randomized clinical trials and maybe bring this information to the public awareness, but one thing what struck me in your comments is there is no indication for any carotid procedures so that means that we, interventional cardiologists and surgeons are doing a malpractice to patients, how can you say that with the techniques that have been actually in practice for decades with very rewarding results to a lot of our patients? Well maybe there are technical results which are good in certain places, other places they're not getting such good results actually, but there's no current proven indication because all the carotid procedures are done based on randomized trials of surgery in data rectomy versus just medical treatment. They were done up to patients recruited now up to 37 years ago so the studies were done roughly 20 to nearly 40 years ago they're all out of date so there's no current evidence of benefit so even though we're doing a lot of procedures in many countries around the world there's no evidence that we're actually benefiting these people in fact there's quite a lot of evidence that we've been harming them. So let me ask you a specific question, so you basically say that there is not a single patient that would benefit from either carotid and rectomy or stenting in any kind of scenario? Not proven. Okay in any kind of scenario so let me again mention a patient that has a 90% symptomatic carotid stenosis and needs a major cardiac surgery you would submit that patient to surgery without considering doing anything for the carotid stenosis? Well certainly they should be on medical treatment because all the medical treatments are dressing risk factors like blood pressure, smoking, cholesterol, alcohol, diet, exercise all those things. But you cannot smoke, you cannot smoke during the procedure. That's good. So that's good but what I'm trying to say there is clear cut evidence that open heart surgery one of the major risk factors of having complications is critical carotid stenosis. Are you talking about symptomatic people with carotid stenosis? Right, right, symptomatic so what would you do with a patient that has a 95% carotid stenosis and has to undergo heart surgery? Whether they have to undergo heart surgery or not I still advise people who are symptomatic and have an ipsilateral carotid stenosis of at least 50 to 70% depending whether they're male or female depending on the timing of when that last event was but for certain people who are symptomatic I would still recommend endarterectomy not stenting endarterectomy with medical treatment. But I have to explain to them still that the evidence for benefit over just the medical treatment is very old. Right so now you do accept that there are certain scenarios where it's not currently there's no it's out of date evidence but still it's the only evidence we have in that situation it's not current but for asymptomatic people it's a bit different because we have measured their stroke rate with just medical treatment over time we haven't done that with the symptomatic people so we now have evidence that actually for the asymptomatic people that they do better with just medical treatment. So do you think of course you're a neurologist you are noninvasive and you treat medical patients do you think that the great majority of vascular surgeons would accept your point of view that the great majority of patients with critical carotid stenosis were symptomatic symptomatic that have to undergo surgery of some kind do not need an intervention on that carotid? Well firstly I didn't say that so whether they need a surgery on their heart or somewhere else or not if you just look at the carotid if it's on the same side of the symptoms of the stroke and the TA the same side of the brain affected I would still recommend endarterectomy with medical treatment telling the patient that data was you know was collected years ago decades ago and but yeah I would still recommend that. And then then if they've got an indication for heart surgery like if they've got unstable angina right you really have to weigh up one thing against the other what is more urgent like if the stroke or the TA occurred months ago if it was female patient if it was less than 70 percent stenosis those people in general are less likely to benefit even from endarterectomy so you weigh that up against the risk of their heart so sometimes you would go ahead still and do the heart procedure if that is indicated and not worry about the carotid it depends on the situation the details. Well I understand your point of view and let me try to be simplistic because some of the audience might be lay people that do not understand the concepts and the details and randomized trials and so on but the point is that if you go to a barber you get a hair cut if you go to a surgeon you get endarterectomy if you go to international cardiologist or radiologist you get carotid artery stenting if you go to a neurologist you get cholesterol lowering medications to simplify it in a way so it means are we are we trying to promote what we know what we can do or is it just a fair to say that there is such a preponderance of evidence available that medical treatment is the only treatment that's reasonable everything else is not reasonable. I think medical treatment is still the only treatment that there's current evidence that it benefits the patient and it's worthwhile it's still worthwhile treating blood pressure cholesterol helping them stop smoking and not drinking too much alcohol and having a good diet and exercise there's still evidence for that but unfortunately there's no current evidence for the benefit from a carotid procedure that's just the way it is. Can you tell me for the last few decades what are the latest advances and the most appropriate treatment as far as medications are concerned and changing lifestyle for patients with cerebral vascular disease? Well over the last three decades to four decades we can look at people with asymptomatic advanced carotid stenosis so these are people with at least 60% or 50% narrowing of their carotid with no previous symptoms of stroke or TIA involving the same side of the brain and we've measured as I mentioned their stroke rates have been measured reliably over time since the first reliable estimates were made in the mid-1980s and since the ACAS trial was done for instance and overall there's been at least a 65% fall in the average annual rate of same-sided stroke so the most recent measurements from reliable studies approximate a rate of about 0.8% per year, it's less than 1%. But what I wanted to ask you actually look at the three decades in the back, medical treatment three decades ago and medical treatment now this is what I wanted you to mention because some of the participants in this. What does it consist of? Right well that's very interesting question like in those studies over time the nature of the medical treatment given to the patients was usually very poorly if it all described. Right. That's because for all these years we've taken for granted the importance of medical treatment it is and the effect it has on stroke rates and therefore the importance to document it but overall what they were given reflected what was usual at the time in practice with respect to diagnosing and treating those risk factors I mentioned before and over time we know that the definition of those risk factors high blood pressure high cholesterol diabetes they've all changed they've all become more sensitive so we're treating people earlier with drugs and also the drugs to treat those risk factors have improved a lot so of course the statins were introduced but they've only had an impact relatively recently so they only became more widely used people especially in people with coronary disease from about 2000 by then the fall had already started so it's not just statins also blood pressure tablets are better well tolerated as well and generally more effective and people have generally stopped smoking as well they've tended to stop smoking so the public health campaigns are working over that time that graph there's been at least 15% fall in the number of baseline smokers in those studies they're also getting older at baseline across those studies that meta-analysis so that means these people are living longer stroke free lives longer healthier lives with just medical treatment that's very important it is very important yes and those are great achievements as far as a medical treatment is concerned there is no doubt about it more public awareness better recognition of problems risk factors and better medical treatment options particularly now with advances in cholesterol lowering medications with PCSK9 inhibitors which can dramatically reduce the cholesterol levels and hopefully even reverse to a certain degree not only karate disease but cardiac and other everywhere so Dr. Abbott can you tell us a little bit about the information available on asymptomatic carotid stenosis patients okay well well using that information that we know about medical treatment and how stroke rates have fallen over over the decades for asymptomatic carotid stenosis we can now estimate that only about 4% at the most of people with asymptomatic carotid stenosis of at least 50 to 60% could possibly benefit from a carotid procedure during their lifetime now that's not many and it's the best case scenario so I'll just go through the reasoning behind that so from that meta-analysis we saw that the average annual ipsi-lateral stroke rate in the most recent studies was only about 0.8% and the average age of diagnosing the lesion advanced asymptomatic carotid stenosis was about was 70 years in those studies and the average survival of those people was 10 years and about half the strokes occurring in the distribution of the lesion are not actually due to the lesion so there are other causes of stroke in these people like atrial fibrillation and intracranial disease so that 4% figure also assumes that that the 30-day procedural stroke or death rate is always and always is always and everywhere going to be zero so based on those simple calculations you can work out that only about 4% of the most of people could benefit and you can't always have a procedural stroke or death rate of zero so overall to me this means that we have passed the era where a carotid procedure is likely to provide overall benefit for people with asymptomatic carotid stenosis very interesting so what do you think about recent guidelines from Europe that recommend that carotid endoterectomy for asymptomatic carotid artery stenosis if certain stroke risk markers are present such as transcranial Doppler micro emboli plaque progression over a period of time bulky and homogeneous what is your opinion on it I don't think these are good markers to identify people who should have surgery or even stenting if they're asymptomatic with carotid stenosis because most of those markers that are mentioned in those guidelines have not even been shown to identify people at higher risk of intellectual stroke than those people without the marker and where they have been shown to identify those at higher risk of same-sided stroke the annualized stroke rates in the presence of those markers are still quite low a too low to justify surgery or stenting for that matter and none of the markers have been tested using current optimal medical treatment so that means all those rates are artificially high compared to what we can do now the trial their risk stratification studies are out of date and also we haven't done randomized trial to show that those markers identify people who do overall benefit from the carotid procedures and also you'll find that just about all asymptomatic people with carotid stenosis will have at least one of those markers so it's another way of encouraging us to operate or stand all of all the people with asymptomatic carotid stenosis and of course we know that's inappropriate so for many reasons I I would say that these markers should not be used to justify the routine use of carotid artery surgery or stenting for these people one of the burning issues that we have to discuss and very important one is differences between men and women in respect to presentation of symptoms and indications if any for a carotid endoterectomy or carotid artery stenting so we have a certain information available from the literature even though the information is limited as far as women are concerned because they are not represented to the same degree in the clinical trials as men have been that's right and so on and there is a also evidence that there women are more likely to be harmed with surgery or stenting for that particular reason yeah so so you do agree that the future studies are needed to look at this particular issue more in detail so I want you to maybe mention briefly your personal opinion on it because I'm sure you analyzed this in the past as well what is your understanding as far as women versus men and incidents of reverse cerebral vascular disease and complications related to it well men and women are different that's the first point to make and quite often they're treated as the same in trials and in guidelines but this is wrong because women tend to present later in life with carotid artery disease than men and in general they present later in life with arterial disease so you have to adjust for that difference in age at presentation and also women with carotid artery disease if they're just on medical treatment they tend to their risk of stroke falls off quicker than men and women tend to have less aggressive disease to its surgery the surgical specimens show that their plaques are usually smaller and less aggressive so there are differences and then of course there are differences with respect to treatment effects surgery and stenting very good well that is true for all kind of conditions related to women I know in particular as far as abdominal aortic aneurysm is concerned typically the women have will have more challenging anatomy as far as axis vessels or infravenal neck smaller vessels more diffuse disease and the outcomes have not been in the past as good as as for men in many other conditions as well so we certainly need more information to be able to better treat women with this type of a condition let's let's talk about women and clinical trials and I want you to elucidate a little bit more what is what is available particularly related to carotid enteroterectomy trials for symptomatic and asymptomatic patients considering women we're going to go through the symptomatic women first so these are women or men for that matter symptomatic patients they've had they've had a stroke or a TAA involving the same side of the brain as the carotid artery disease the narrowing is situated so when it comes to trials of endarterectomy versus just medical treatment randomized trials symptomatic patients the only women to actually receive an overall statistically significant benefit from endarterectomy compared to just medical treatment were those with 70 to 99 percent stenosis using the NASA measurement method and they had to have endarterectomy within two to three weeks from their last same-sided stroke or TIA but they also had to satisfy other criteria they had to have a life expectancy of at least three to five years and they had to satisfy all the trial inclusion and exclusion criteria and they also had to have no distal lumen collapse beyond the degree of narrowing and also the 30-day stroke or death rate from the procedure had to be less than about 6% to benefit so that's only one very select group of symptomatic women right so for instance no other subgroups of women benefited including the people in the trials women in the trials with with high-grade stenosis 70 to 99 percent NASA measurement stenosis who had endarterectomy after two to three weeks from the last same-sided stroke or TIA they didn't benefit and also women with moderate stenosis 50 to 69 percent narrowing no matter what the timing was for their last same-sided ischemic event TIA or stroke so the symptomatic men in those trials they had they overall more likely to benefit were basically talking about pooled data from NASA and ECST for the women but for the men there was an additional study the Veterans Affairs study so overall for men in those trials using pooled data they still received a statistically significant benefit from surgery compared to just medical treatment if they had moderate stenosis so 50 to 69 percent again using NASA criteria and as long as they had the endarterectomy within two to three weeks from the last same-sided stroke or TIA and interestingly the symptomatic men with very high-grade stenosis so 70 to 99 percent again using NASA criteria they also had a benefit from endarterectomy performed up to about three months after their last same-sided stroke or TIA so they're much more likely to benefit than women and these men in particular that that second group most of the benefit occurred in the first two to three weeks after their last same-sided stroke or TIA and fell rapidly over time but nevertheless after three months they still had a benefit they also had to satisfy all the study inclusion exclusion criteria no distal lumen collapse and the 30-day stroke or death rate from the surgery had to be less than about 6% 6% yeah so was there a benefit for asymptomatic women from the criteria endarterectomy trials no overall there was no clearly statistically significant benefit for women so can you mention some of those trials so the ACES trial has really been the only randomized trial of surgery versus medical treatment alone for people with asymptomatic rod stenosis so just to get that up out there in the front so up there at first so then other trial is mentioned the ACES T trial is mentioned sometimes but that wasn't a trial of surgery with versus just medical treatment because that was a study of delayed versus immediate surgery endarterectomy and by the time the trial finished about 20% of their patients in the deferred arm delayed surgery arm had had surgery and they also included people with remote who are remotely symptomatic so you'd had stroke or TIA in relation to the same carotid artery they were studying more than about three months ago so that the trials weren't the same so ACES is still the dominant trial in terms of justifying endarterectomy for asymptomatic rod stenosis so women did not receive a statistically significant benefit from endarterectomy in ACES and then if you want to consider ACES T the women in that study that came closest to benefiting from endarterectomy they were aged less than 75 so the younger ones and that was only a borderline statistically significant result I see men were more likely to benefit in the trials if they were asymptomatic with carotid stenosis but still not many men benefited they had to be less than 75 to 80 years of age and they had to have at least 60 percent asymptomatic carotid stenosis using the NASA criteria for measurement they had to have a life expectancy of at least three to five years and again they had to satisfy all the trial inclusion and exclusion criteria and the the surgical stroke or death rate had to be less than about we could debate this but it could have to be certainly less than 1.7 to 3% so the 1.7% comes from ACES without the angiographic risk and we probably should have been using that standard all along because we don't do right angiography anymore and the 3% figure comes from the ACES T trial and you could also argue for a 2.3% risk because that was the risk in ACES with angiography what is the risk of carotid endarterectomy for women compared to men well overall overall in all the trials randomized trials of surgery versus medical treatment doesn't matter whether you're symptomatic people or asymptomatic people with stenosis women did worse worse they had a higher procedural risk of stroke or death compared to men and that is repeated basically in all of the trials so this is pretty convincing yeah because there have been other studies that not randomized just observational studies and there's been a meta-analysis for example by Bond et al published in 2005 and it was consistent with what was seen in the randomized trials that women still had a higher rate of stroke or death than men with endarterectomy what about now carotid endarterectomy yes can you mention a little bit about that yes that is for you is definitely controversial so can you all right mention a few of them that have been completed and at least give us some information whether there are any benefits or not they have been lots of randomized trials stenting versus endarterectomy mostly for symptomatic people with carotid stenosis but in all of those trials pretty much and certainly overall stenting has been shown to be worse than endarterectomy it causes about twice as many 30-day periprocedural strokes or deaths than endarterectomy and that risk of stroke or death is not compensated by the risk of heart attack associated with endarterectomy so that's a sort of a common furphy that furphy term that I like to use a misunderstanding or a mistruth it's certainly not true that the risk of heart attack with endarterectomy compensates for the risk of stroke with stenting because if you look at all those randomized trials of surgery versus stenting periprocedural stroke was about four and a half times more common than periprocedural heart attack and most of those strokes occurred with stenting and overall in those trials the 30-day rate of stroke heart attack and death was about 1.6 times higher with stenting so it's quite conclusive from the randomized trials and also from registry data that stenting is much more harmful to patients than endarterectomy. So you know some of the critics of this particular assessment of your or interpretation of this would say well a lot of those trials were poorly designed poorly done and they were actually aborted because of a suboptimal performance of the operators or poor design or trial and I can mention few of them such as space trial that had terrible outcomes because the operators were doing procedures they should not be doing the procedures Eva 3S similar so cavities is totally outdated there was actually a carotid artery angioplasty performed in certain scenarios in this particular trial so we cannot lump all of those trials together and say in general that all of them are bad as far as carotid artery stenting is concerned because some of them were just not well and properly designed. Nevertheless we haven't shown that stenting benefits any patient with carotid artery disease right on the basis of this information that's all the information we have suboptimal trial that's all we have right so there's there's still no there's no establishment of a routine practice role for carotid stenting so for instance another criticism might be crestar trial was pretty reasonably carried on in experience centers by experienced operators even though there were little trends and differences as far as complications and morbidity is concerned and mortality between carotid artery stenting versus endoterectomy this was not statistically significant and yet you claim that there was a significant difference but the p-values were not significant. In the Cress trial it was certainly statistically significant that stenting causes more 30-day strokes or deaths than endoterectomy for symptomatic people and then when it comes to the asymptomatic people or the people with asymptomatic carotid stenosis no statistically significant difference but the study was underpowered the confidence intervals overlap one but the trend was still towards nearly twice so there is a trend but no statistically significant difference if you had have had a larger sample size it's highly likely that you would have shown that stenting causes a nearly twice as many strokes or deaths in 30 days of the procedure compared to endoterectomy if but there wasn't so that information is not there it's just a speculation that it would happen right well that's why you need larger sample size before you can establish a routine practice role for this procedure so you could say that it's inconclusive you could say but I've understood that recently Ross Nailer published a meta-analysis there is evidence now that with the largest samples all pulled together just asymptomatic people that they're showing that stenting is more dangerous than endoterectomy statistically significantly and the other studies that you would like to mention related to this particular issue well I haven't mentioned that endoterectomy stenting of course has not been compared to current optimal medical treatment so that's the other thing so there's no there's no basis for saying that stenting should be done as a routine practice treatment for anyone with coronatory disease a lot of people are at particularly high risk of stenting too like if you've just recently had your ipsilateral stroke or TIA you're many times higher at higher risk of having a procedural stroke than compared to endoterectomy and women are particularly susceptible and there are quite a few other thing markers that put you at higher risk from stenting so there are some newer trials in the ongoing at the present time mm-hmm and one of them is crest too yeah that wanted to address this particular issue of advances in medical treatment of karate artery disease and comparing medical treatment to surgery and medical treatment to karate artist stenting can you mention briefly your opinion on whether crest two is going to give us some of the answers and what are the positive things about crest and what are the negative things about crest in your personal opinion well I think though the biggest positive thing about crest two is that after a long time of just having randomized trials of stenting is versus endoterectomy they're finally having medical treatment considered as a standalone effective treatment and it's it's a it's an arm on its own in this trial whereas the other we've not been doing that in previous trials anyway so it's actually a study of two randomized trials running in parallel mm-hmm so they're comparing endoterectomy versus medical treatment on its own both procedural arms have medical treatment as well and then the other trial is stenting with medical treatment versus medical treatment alone unfortunately I think though the overall the trial is both randomized trials are going to be underpowered because what they're doing is they're taking average surgical risk people with asymptomatic coron stenosis of at least 70% and they're randomizing them to medical treatment versus a procedure but we already know we already know from what we've just discussed and the studies have been done since a cast that these people are unlikely to benefit from a carotid procedure overall mentioned that 4% figure at the moment at most 4% are likely to benefit from a carotid procedure during their lifetime as long with the procedural stroke or death rate is always zero which is not possible so in other words I feel that we've passed the era where a carotid procedure is likely to provide overall benefit for a generally fit person or any person for that matter with advanced asymptomatic coron stenosis right well thank you very much for visiting our institution Texas Heart Institute it's a special pleasure to have you as a guest at our institution and we greatly appreciate your expertise and knowledge and information provided to us related to carotid artery disease carotid intervention medical therapy what works and what doesn't work thank you very much thank you very much