- Thank you very much, Ally. I don't know if it's more insulting to be told I work in London or that I'm English. I have no disclosures relating to this talk. I'm going to speak to you today about a subject where people have an awful lot of opinion, but it's based on very little evidence.
This is the 14 society guidelines on the management of restenosis after endarterectomy or stenting. And although it didn't actually publish a recommendation, it stated that it's benign, doesn't require revascularization, except where it leads to recurrent symptoms or preocclusive severity.
And in that situation, it's reasonable to intervene. But if you look at a meta-analysis of all the papers published on the management of restenosis, two-thirds were in patients who were asymptomatic, so clearly, there is a great deal of concern for surgeons and interventionists about
not treating recurrent stenosis. Our group addressed this in a systematic review and meta-analysis, and we used randomized, controlled data, not observational studies. We used four randomized trials comparing
stenting with surgery including CREST, EVA-3S, and Space, and four randomized trials of various different types of patch closure with endarterectomy, including three from Ally's group. The key things about this was that in addition to the normal data,
we asked for the stenosis severity before stroke onset, not after they'd had their stroke and then looking, and that's quite important. And we chose randomized trials because they're prospective, they're conducted with greater scientific vigor, selection bias is reduced, and most importantly,
there is independent scrutiny of the endpoint. Now, part of the study was to look at the incidence of restenosisa, and we had 11 randomized trials for that. And you can see, after any type of endarterectomy, the restenosis rate greater than 70% is 5.8% at four years, for patched, it's 4% at 32 months,
and for stenting, it's 10% at 5 years. But does this translate into increased stroke risks? Well, here's the CAS data, four randomized trials, nearly 2000 patients, four years of follow-up. And what's absolutely clear here is that if you develop an asymptomatic restenosis
after stenting, you'll virtually never suffer a late ipsilateral stroke. You are more likely to suffer late ipsilateral stroke if you do not have a restenosis. Conversely, here's seven randomized trials with nearly 3000 patients, three year follow-up.
There is a small but significant increase in the risk of late ipsilateral stroke in patients with a 70% to 99% recurrent stenosis, and although the odds ratio is approaching five, what you're dealing with is 5.2% with a restenosis versus 1.5% without a restenosis.
So for CAS patients with an asymptomatic restenosis greater than 70%, you're highly unlikely to ever get a recurrent stroke. And if you intervene on all of them, 97% of all ipsilateral strokes will still occur. But for the endarterectomy patients
with an asymptomatic restenosis, there is a small but significant risk. But you have to factor in the risks of retreatment, and this is a meta-analysis from Holland, showing that if you treat restenosis with stenting, the death stroke rate is 2.3% versus 2.7% with surgery.
So what does this mean? Well, 66% of endarterectomy patients will develop a restenosis. You need to screen 1700 in order to find 100 patients with a recurring stenosis, and if you intervene on all of these,
you might prevent five late strokes, although I think that's doubtful. But you will cause two to three. And if you treat all of them, 85% of all ipsilateral strokes will still occur, because they happen in patients
with restenosis less than 70%. So unless you can intervene with a death and stroke rate less than 1%, there's really no meaningful benefit. And this was taken on board as part of the evidence for
the recently published European guidelines. If you're symptomatic, then we definitely advocate redo surgery or stenting. We advise that reintervention may be considered in endarterectomy patients with an asymptomatic restenosis,
but following MDT review. And we advise that the CAS patients should be treated medically. There were two caveats, and these were patients who either developed neurological symptoms during carotid clamping
on the local anesthetic, or during balloon inflation during stenting, i.e. these patients will not tolerate progression to occlusion. And therefore, surveillance and reintervention is appropriate. And we also extended this to patients
who had EEG or SSEP evidence of changes with carotid clamping, or who had very low velocities under GA. And if you want all the evidence that we used to develop these recommendations, they're all in the latest carotid guidelines
from the European society. Thank you very much.
- Wonderful, thank you, Nick, thank you, Dr. Abourahma. So this is an update from the SAMMPRIS trial. This is a stenting versus aggressive medical management for patients with symptomatic intracranial atherosclerotic disease.
So we're not talking carotid disease. It's intracranial, and I want to acknowledge here Mark Chimowitz, who's the neurology PI for the trial, and Tanya Turan, who helped develop the medical regimen
that we used in the study. So what is good medical therapy? Essentially, for intracranial, lateral, and probably by extension, for carotid disease, it's antiplatelet agents,
dual for recent symptoms, at least for 30 days, if not 90. It's good systolic blood pressure, less than 130, less than 140, or 130 if you're diabetic. An LDL cholesterol less than 70.
Some modest physical activity, and smoking cessation, and again, this was the regimen for SAMMPRIS, and it's been the regimen that Tom Brott, who's here, has adopted for CREST 2 as well.
It can be done, and this is probably the most important slide for the first part of this nice complicated VEITH talk, with two subjects, and this is the tolerance here.
So this is the time on enrollment, and then this is after three years of followup, and you can see that for LDL control, we went from 20% to 60% or so. There's also a very nice benefit for physical activity.
People that started walking, and generally physical activity, was just walking once a week, if not three times a week, and compliance was defined as once a week, but we went from 30 to over 60.
Also, a good control of blood pressure as well. Not so good for diabetes, or for weight changes, or for smoking cessation. And these things really mattered. This is odds ratios
looking at risk factor control and the three year risk for stroke, MI, and vascular death, and the most powerful of all the risk factors really was physical activity. If people self reported that
they walked once a week for 30 minutes, they had a much stronger, a very dramatic benefit in terms of the risk of any of these vascular endpoints. Also significant in a multi-variable model was LDL, systolic blood pressure, and HDL.
Okay, so that's it for it can be done, and now let's talk a little bit about ISR, which follows nicely on Dr. Naylor's talk. So this is an angiogram, AP of the carotid, showing a tight symptomatic MCA stenosis before and after stenting,
with the wingspan stent, and here's the markers of the stent. And then sometime later, a few months later, we have a tight long segment knurling here, with some recurrent symptoms.
The SAMMPRIS, we did not have surveillance for ISR, for in stent restenosis, but most of the patients that developed a stroke or ischemic symptoms underwent vascular imaging and we have that available. So of 224 patients that were randomized
to the stent arm, 183 had no 30 day endpoints, no peri-operative procedures. Of the 183, 27 of these had either a stroke, or a cerebral infarction with temporary signs, which was not an endpoint in the trial,
but essentially, this is a clinical TIA, with the diffusion weighted image abnormality. Of these patients, 24 had vascular imaging that was adequate to assess for ISR, and we found ISR in 67% of them.
Another 16 patients had TIAs during this followup, and 10 of those had adequate vascular imaging. Eight of the 10 had ISR. So these are annual rates for symptomatic ISR, not asymptomatic.
After intracranial angioplasty and stenting, and they are conservative because we didn't assess for ISR in all of these patients, and vascular imaging wasn't available. But at year one,
7% developed asymptomatic TIA, CITS, or stroke, 8.9 at two years, and at three years, 11%. In terms of what ISR was associated with, none of these are significant in multivariables,
but a trend for higher cholesterol, a trend for smaller vessel diameter baseline being associated with ISR. So in summary, for ISR, symptomatic ISR is a major barrier to the success of angioplasty and stenting
for intracranial athero disease in the SAMMPRIS population. The three year risk of recurrent stroke after peri-procedural events was about 10%, and this was essentially the same as that in the medical group.
So, even if the peri-operative complication rate had been zero, the outcomes in the two groups would've been about the same, which is a real concern for this procedure in this population.
And symptomatic ISR was not strongly associated with any baseline characteristics, and as I noted, the study underestimates ISR incidence. Thank you very much.
- Thank you so much. I want to thank Professor Veith for the kind invitation. We know from literature that cognitive disorder can be related to carotid occlusive disease. This is why, some years ago, we published this paper concerning results, and Mike Remblai observed more in CAS patients when compared CEA patient,
and demonstrating that in patients omitted to standing post-operative neuro psychometric had a drop immediately post-operative and at six and twelve months, more importantly when compared to carotid inner traction patient, we also observed a trend in increasing some
neuro biomarkers in CAS patient that was not observed in CEA patient and this is in line with what published by Professor Zhou and her group that found that Systemic biomarkers can be used to detect pts at risk of significant cognitive decline following a
carotid revascularization procedure. And Professor Zhou also demonstrated in CAS patient an increased load of microemboli when compared to carotid inatracme and she has the merry to have demonstrated that the impact of volume correlates negatively with cognitive decline.
This is in line with a finding with another study that I'm going to present later in this meeting In which we randomize 58 pts to corodistanding with Cgaurd or Wallstent and we found in those patience that those presenting more than 5 lesions at post-operative DWMRI has a drop in post-operative score
in both Mini-Mental State Examination test and MOCA test. On the contrary in literature we have some experiences that showed an improvement on the contrary in patient in cognitive in performance in patients emitted to standing when compared to endarterectomy. Although there's some group reporting no difference
and no significant difference in patients emitted to endarterectomy, transfem CAS or transcerv CAS in terms of cognitive performance, but in this paper they should a higher emboli load in transfem CAS when compared to the other procedure.
To summarize, the systematic review shows that nowadays we have no evidence and no significant cognitive difference was found between the two operations. Nevertheless cognitive tests, we have to remember that tests differ in function in areas into the brain and they can be effected by practice of course
this is why those eight others propose a correction factor to be applied when evaluating repeated tests in our patient in order to avoid a misinterpretation of posture revascularization scores in those patients. We also have to acknowledge that cognitive tests can be effected by brain connectivity,
what is the connectivity? That is the modularity of our brain, and the study of brain modularity can help identifying patient at risk of developing cognitive impairment. Something really happens into the brain
when you have micrambly going there. The problem is that we are not yet able to fully understand the significance of those micrambly. Maybe the definite answer can come from the CREST-H in which a sub group of patient will be studied by cognitive assessment following medical treatment or
carotid revascularization, but to conclude the effect of carotid revascularization and cognitive function have not been clearly established. Cerebra plasticity can account for different effects of carotid revascularization on cognitive performance, and perhaps metabolic imaging can help understand
relationship between perfusion and cortical functions in different brain areas. But for those who do not believe that micrambly can cause something, I'm going to show you this short video on a patient that had possibly DEMRI lession, she was a painter
and a poet but when asked there, you can see a perfect cube, a perfect circle but when asked to put the hands of the clock on 10 past 10 she was not able to put the hands on it and you can see the number that she draws.
So please bare that Neurocognitive decline can deeply effect the quality of life of our patients, so thank you for your attention.
- Thank you. Thank you, Mr. Chairman. Thank you, Franc. Franc propose me, suggest me to talk about that topic. Quite provocative, a little bit. No. First of all, what is a minor stroke definition? We can...
We all have in mind the vision of a stroke, classical stroke, a patient that fall hemiplegic with aphasia, but not all the stoke look the same. We can either define a small volume stroke, occurring in very functional area
that we call strategic small infarct. Or stroke without immediate clinical expression, but that impairs cognitive function with time. So, some few example of small strategic stoke: this is patient that has been treated of an Acom aneurysm. He awoke without any motor deficit, no sensory deficit.
However, when we spoke with him, he had loss all the recent memory. This is a Korsakoff syndrome, due to an infarct of a perforator feeding the trigon area, which is an area that participate to the (mumbles). Another strategic infarct in the anterior part
of the thalamus, leading to the same loss of recent memory. My first message is that the brain functionality, of course, is not limited to body muscle command. The memory, judgment participate, to what I could call, the honor of human being. And the cognition can be altered by infarct
of either strategic areas, or by bilateral multiple small infarct, whose best example in clinic is the small vessels disease of the brain. Small vessels disease of the brain is much more frequent that we believe, probably more frequent
than carotic diseases, due to lesions of arteries of the brain below 400 micron in diameter. It's done of narrowing or occlusion, not by arteriosclerosis, but by arteriolosclerosis. And it lead potentially to a status called vascular dementia.
This is a review you can find in Lancet Neurology about this disease. So vascular dementia is the second most common cause of dementia after Alzheimer's disease. Symptoms include cognitive dysexecutive slowing, forgetfulness, dysarthria, mood change.
And the main risk factors of this disease are, first, the advanced age, hypertension, diabetes, smoking, probably genetic factor. At the beginning of the disease, the MRI show typically disseminated area of FLAIR hyperintensity, and the large vessel,
the large arteries, are normal. With time, the hyperintensity become confluent and can be associated, as you can see here, with true lacunar infarct. That, once again, the sign must be bilateral in this disease.
And the dementia with lacunar state is a multiple disseminated infarct, less than 15 millimeter in diameter, located in subcortical area, and once again, bilateral. And you can see here, in the deep area of the brain. Dementia mechanism of the unit cell is probably due to
disconnection of the fibers that connect the frontal cortex and the basal ganglia. By parenthesis, if you see in such a patient, if you discover a tight ICA stenosis, such an aspect of the brain is, to me,
a very poor indication for any kind of intervention on this stenosis, because it would not change the prognosis of this patient. So, whatever their mechanism, embolic or arteriolosclerotic, multiple small cerebral infarct can definitely
lead to cognitive decline and, therefore, are not benign. Thank you very much.
- So, we have some new data on this topic form the Journal of Vascular Surgery just this year. It's a retrospective review of 3382 patients with stroke single-center Mass General hospital, a cohort study. And so what they found is that 219 of the strokes occurred in previously asymptomatic patients with ipsilateral carotid stenosis greater than 50%.
They did not look at patients with less than 50% carotid stenosis which we'll mention a little bit later. The distribution of these strokes in these patients, as you can see, the largest percentage in patients with 70% carotid stenosis, 70% or greater. But a little bit of a surprise was that 43% of their
patients actually had carotid occlusion. 10% had 50%-70% but remember, they did not include patients with less than 50% and I can tell you now at Mayo clinic, when we have a patient who we can't figure out the etiology of the stroke, we're doing 3T Tesla imaging of the carotid plaque and just like
with atrial fibrillation when we do monitoring for atrial fibrillation over time, it may be that in this group of less that 50% carotid stenosis, we'll learn something over the next years to indicate that some of those patients are having their stroke from sub 50% carotid stenosis.
You would think that perhaps carotid occlusion would result in an infarcact like this, but we really don't know. And I think the Mass General group just has a gold mine with these 219 patients with regard to their imaging, brain imaging, with regard to their carotid angiograms and they had quite a few and their other vascular imaging
and I've already been in contact with them so that this talk, Frank, I see you down there, can have more meat as they mine this gold mine of information from these patients with bifurcation disease and stroke. Interestingly, this is about lipid lowering therapy and platelet, anti-platelet therapy
and those with anti-platelet therapy and lipid therapy were more likely to have a milder stroke. And that's important, but what's also important for me is you look a how these severe, how severe these strokes were and again, you can see almost 80% of those who were not on anti-platelet therapy and lipid lowering
therapy had a severe stroke. So these carotid occlusion patients said they didn't break it down by that, certainly had odds to have a severe stroke. The authors conclude "the results of the present study question whether medical therapy is sufficient stroke
risk-reduction strategy in asymptomatic patients." So this complements the data that we already have from ACST, you know it's been a long time since we had a medical group in a randomized trial. And in this study, we had 212 strokes and you could see about 6% were hemorrhagic, 12% roughly were
cardioembolic, 50% were other ischemic, and you could see that almost 25% were unknown. Well we've got technology today and so again for a talk like this, we hope that CREST-2 can help. We already have 605 medical-only patients with 625 more to come.
We've got 3T plaque imaging, you know how does this help? What is the role of hemorrhage within a plaque in cause of stroke? We have baseline perfusion imaging as already mentioned by one of our speakers, with MRI or CT perfusion. You know, what types of strokes occur in patients
with hemodynamic compromise? And then we'll have MRI on any suspected strokes or TIAs, which wasn't the case with ACST and it may be that some of the strokes that we call A or we call B or we call lacunes, aren't really those identities. We have end of study Brain MRI.
How many silent strokes are coming from the carotid bifurcation? What do they look like? What's the outcome? What's the outcome with regard to cognitive function? We have cognitive function measures on all of
our patients as well. In all of this new, we hope that 21st century data will have adjudication by skilled individuals. And with that I'd like to close and again, thanks again for the invitation and the opportunity to participate in this great conference.
- Thanks Nick and thank you Frank for the invitation. I'd like to the privilege to talk about the CREST-2 Registry on behalf of the B.K. Lal, Tom, and the entire CREST-2 management committee and the enrollers and the investigators. And it won't click. Left hand click, right?
Sorry. I can't make it move. - [Moderator] Advance the slide please. - You're taking my valuable time away. (men laugh) Okay, this is my conflicts of interest.
You have to advance it, 'cause the left hand clicker is not working here. All right, we all know that for the CREST-2 study, the primary aims are to look at patients with greater that 70% asymptomatic stenosis, to look at outcomes between intensive medical therapy alone
versus intensive medical therapy with revascularization either with carotid endarterectomy or carotid stenting and looking at stroke death out to four years. Next slide please, thank you. This is really two studies and one of those two studies
is the carotid artery stenting arm. This trial began enrolling back in 2014 with 150 enrolling centers and 2,500 patients. Next slide please. So what about the CREST-2 Registry? What is this and how did it come into being?
Well recognizing that there's a disconnect between FDA approval and payer coverage, the only pathway for carotid artery stenting for asymptomatic patients has been through studies like PMA studies and that has led to an operator experience gap if you will,
because of the lack of those studies. This presents a conundrum for that first study within the CREST trial. Next slide please. So as an example, when we first went to do the credentialing for carotid artery stenting in this trial
we set a standard for 100 lifetime cases, 25 cases within the past 12 calendar months. And in the first 25 candidates we looked at, zero were credentialed and in the first 50 only two fit that criteria. Next slide please.
So the primary objectives of the CREST-2 Registry were to enhance the enrollment in CREST-2 by credentialing high quality operators and giving them some experience. Next slide. Secondary objectives were to allow for accrual
of experience in existing and new operators and to help them to acquire standardized techniques to eliminate these variances in technique and in skill level and to look at the contemporary results from carotid artery stenting and outcomes from experienced operators
and establish benchmarks for quality. Next slide please. So here you see we have a site. This is the operational aspects of the CREST-2 Registry with operator selection by an interventional management committee,
carefully reviewing their data, collecting the data using a combination of the SVS VQI Registry and the NCDR-PVI Registry which is a nice merging of these two with supplemental data forms
so that they're actually identical. Collating the data and analyzing the data, both for operator credentialing and feeding back to the CREST-2 management committee to get randomized operators. Next slide please.
Here you can see on the right that a number of applicants to a number of operators who applied to be CREST-2 operators were actually denied based on the results that we obtained from the registry. Next slide.
So here we are as as of last month. Carotid stenting procedures in the CREST-2 Registry and we have a total of 4,064 of which 3,209 were CREST-2 Registry eligible. And of those 1,809 were asymptomatic and only 153 were actually eligible for randomization
within the trial. So most of the patients that are randomizable, are actually put in the trial. This is from 98 U.S. sites and 184 interventionalists and the typical comorbidities and so on. 34% female interestingly,
but otherwise pretty standard. Next slide please. So the data through 9/30/18 show that we have used that operators are using the full range of FDA approved stents and embolic protection devices. Filters in 86% and flow reversal in 14%.
The outcomes are to be presented at the International Stroke Conference in February. Next slide please. Next slide please. As predicted, the CREST-2 Registry has helped enhance CREST-2 enrollment,
by getting appropriately credentialed operators. You can see that about half, 49% of the enrollment in CREST-2 is from the carotid artery stenting group and this would never have happened without the CREST-2 Registry.
Next slide. In summary, the challenges addressed by CREST-2 Registry are to help with the declining procedure rate and to augment the procedure volume, to generate a generation, develop a generation of operators with adequate expertise and maintaining this,
and ultimately to help the CREST-2 enrollment to answer the question. Next slide. What we've learned is that there's great variation in experience and technique still. There are significant deviations,
remarkably from standards of care and standard technical expertise. You would be surprised at some of things that we're seeing as we review these people's experience. And CREST-2 Registry will provide a platform from which to educate, inform,
and train operators in a positive non-threatening way. Next slide. And our future plans are to maintain this registry throughout the conduct of the trial until the trial is published, to analyze and publish the data
and it will help us report the contemporary outcomes for carotid artery stenting, analyze the variations in technique and outcomes and so on. Next slide. Hopefully this will provide a segue to a new coverage decision.
We believe that this is a template for a monitored registry if you will, well we can actually look at the operators on an ongoing basis and also have some degree of oversight and a require for data submission which I think should be a prerequisite
for any carotid stenting.
- I might start by asking Ross, if I heard you right, it sounds like restenosis after carotid stenting is potentially a less dangerous thing than restenosis after endarterectomy. And I'm wondering if you would tell us what you think is why, number one? And number two, does that tend to make you think
that carotid stenting is just as good as carotid endarterectomy, overall? - Okay, there's two questions there, Nick. The first is, why? I can't answer that. This meta-analysis we did was the first real
quality data to be able to come out to suggest that once you'd undergone a successful stenting procedure, the risks of late ipsilateral stroke are very low indeed. So I can't answer specifically why. The second issue is, is stenting now as good as surgery?
If you go from 30 days onwards, yes it is. It's just the same. As Gerrick de Borst and I wrote in an editorial in the European Journal, in the end it all comes down to the beginning. And it's all about the 30 day risks that determine
which is the best intervention in individual patients. And it will vary according to individual patients. And the key thing for the future is getting the risk, 30 day risk of death and stroke down, in stented patients. I've no doubt in the future, yes it will, will all the technology.
That's what's happening in every vascular bed. But right now I don't think it is. - Ross, follow up with the same. Does this mean we really don't need to do any surveillance after CAS since, literally, we are not getting any benefit at all?
And it's unfortunately both European guidelines and our SVS guidelines recommending surveillance with frequent monitoring and ultrasound. - Well ours don't. The European Society guidelines do not recommend serial surveillance.
There was a heated debate within the writing group and the consensus based on evidence was that it could be justified in surgery patients 'cause of the increase risk of stroke. But the differences are small and you have to have really low complication rates
in order for it to be beneficial. But I must admit in my own practice, and that's the way I interpret literature to act in my practice, we've stopped putting the stent patients in surveillance, whereas we always did beforehand.
And we've never surveyed the carotid patients anyway but we now put it in those who have very low flow rates during carotid clamping, because they will not tolerate progression to occlusion. So it has made us change our practice but perhaps not in the way people anticipated.
- We have a colleague from New Orleans here. - Thank you. Professor Anieder Hernan Berzant from New Orleans Clinic. There's some thought, and we have some clinical evidence, there's some thought that perhaps the pathogenesis required at stenting restenosis is not really
atherosclerosis but it's really perhaps patients aren't maintain or aren't compliant or are resistance to Dollente platelets. Maybe they're clopidogrel resistant. Their restenosis is really from platelet aggregates and not really atherosclerotic disease that advances
like perhaps for late carotid endarterectomy that we see three, four years progression of atherosclerosis. Do you have any evidence from looking in your data set if the carotid stent patients that restenosed, were not compliant on Dollente platelets?
Or any of them clopidogrel resistant and that was really the mechanism for restenosis, versus progression of atherosclerotic disease? - Unfortunately I couldn't. The acoustics are a bit dodgy here. - I apologize.
- I think the first comment I heard you say was that restenosis was associated with anti-platelet therapies. - Well there's some thought that for carotid stenting. - I would dispute that. I'm not sure there's any compelling evidence that mode of anti-platelet therapy is predictive of
whether or not you going to get a restenosis. If it was, then life would be an awful lot easier. With regard to clopidogrel resistance, I think it's well accepted that about 10% are resistant to clopidogrel. But I've not seen any work showing that that
increases the risk of restenosis. If you're aware of it then I'd be very interested to know. Unfortunately I couldn't make out the other question because of the acoustics. Could you make it out? - Actually I have the same trouble as you do.
Do you want to try again maybe with the. - The question is, so you have no evidence that, you think carotid stent restenosis is similar, it's a similar pathogenesis to carotid endarterectomy restenosis. - Okay. We didn't look at that because
one of the things is that virtually, well nobody had any interventions done. That was the whole point of it, that these were randomized trials where there was no re-intervention. And therefore nobody knows what the lesions were like. I can't answer therefore whether restenosis after
endarterectomy is the same as restenosis after stenting. - While we have nobody from the audience, Laura. Do you think with your findings should the subclinical MRI Bay lesion be considered as a primary influence when you compare stenting versus endarterectomy. - Really, I think so.
I think we have to consider the possible effect of those subclinical lesions on cognitive performance. I think in fact must try, we should test this. - I'd love to hear the panel's thoughts on cognitive function in general. I think, how many people in the audience
have done an endarterectomy and then noticed from the patient or his family that the patient has gotten significantly better in your first post operative visit? I usually ask about crossword puzzles. And sometimes there's no effect.
But every now and then you have a patient who comes in and, oh yeah, my god, he's doing things now that he couldn't do before. How many people in the audience have seen that phenomenon? We don't have any data but I think it's obviously anecdotal.
- Can I just mention, you got to be careful with that. Of course, as we all know, in the TPA randomized trial I took care of 150 of those patients. And almost all of the patients that improved, they and their family concluded that they got TPA. So when you get a meta-center, you get an operation,
you go back to see the surgeon, how you doing at crossword puzzles? Well, since you did my operation I'm terrible. I mean, you know that's, that's. You got to be careful of that. - Well, that was the first part.
The second part was if you look at the data, I mean it's all over the map. There are some studies that show improvement in cognitive function. Others, probably the majority, that show a worsening in cognitive function.
And one of the big problems, I think, is the fact that we still don't have a really well standardized set of tests to evaluate cognitive function after these procedures. And so, Tom, where are we going from here? - Well, in the Cress trial, we have
a cognitive battery that was put together by Ron Lazar and other neuro-psychologists. And it take about 25 minutes. And Ron would be the one to tell you about, that it's validated, that the results are normal, that the Z-scores work, and we're debating that right now.
So we're looking. And then CREST-H, about 20% of patients with carotid disease on perfusion or CT perfusion, MRI perfused CT perfusion, will have a deficit of perfusion. And we're doing cognitive testing on those patients before and after, to help there.
So hopefully we'll learn some things, 'cause we've got of course, two groups, and everything's blind which helps for you and me who are optimists. - Yeah, the fascinating thing is if you, Ron Lazar did all the studies for the Claret trial as well. And they really couldn't come to a significant conclusion.
Even though 98% of the filters in that trial had debris in them, which is interesting. - I think, so and Ron also did it for Recon, for the cost trial, the BCIC bypass trial. And we were unable to show an improvement. We were unable to show a difference of improvement
between the surgical and the medical group for the cost trial, in terms of neuro cognitive outcomes. Probably because both of them improved at the same rate in terms of improvement in collateral flow. I think it really comes down to,
and it came out in your talk a little bit, about how we have these competing impulses of microscopic injury and in some sub-group of patients, almost certainly hemodynamic improvement. But they compete and it's, and we don't have it teased out yet.
- You think it's because we're not looking out far enough, maybe? It may take years, 10 years before we. - Well that, that gets tricky because of course the patients come in at age 70. And they come in to your office of course
with a bag of medications and a history of 10 different problems. So, over time, from 70 to 80, a lot of other things are happening. So it may actually get harder to see, the further out you go.
- You know, I was asked to give a talk about this at VIVA last week. And it was a new topic for me. And my hat's off to BK Lau who's done a lot of work on this. But as you explore the topic,
if you have ischemia and other beds from diminished flow, you have effects. In the heart you can get cardiomyopathies. In kidneys you can get renal dysfunction. And so why should that not be the case with the brain. We've always assumed it's only artery to artery
embolization that causes cognitive deficits. But I think it's much more than that and this story is untold. It's really interesting. - Yeah. Thank you very much.
- Ladies and gentlemen, it is a privilege to be here. Thank you Frank, for the invitation. I'm starting the debate for my opponent. You can see here, Professor Eckstein, for his distinguished and prominent member of the European Society of Vascular Surgery. But he has a difficult task to do.
Look at recommendation number 39 of the European Society of Vascular Surgery that was published a few months ago. Carotid endarterectomy or carotid stenting are not recommended in symptomatic patients with a chronic internal carotid near-occlusion,
unless associated with recurrent ipsilateral symptoms despite optimal medical therapy and following multidisciplinary team review. This last sentence, a small concession to my opponent. Reduction of flow across a near total occlusion may decrease the shear stress on the plaque
and the risk of embolization. TCD has shown a significant reduction of microemboli from the internal carotid artery stenosis, if it is more than 90%. The hypothesis he used is the clinical behavior of near total occlusion may be significantly different
from lesser degrees of severe carotid artery stenosis, hence there is a need for closer scrutiny of this group of patients. And the diagnosis of near total occlusion is not a deniable test, you can see criteria set down by Fox and colleagues many years ago.
And this is an example of how this criteria apply. You can see delayed arrival of contrast in the internal carotid artery on a patient with near total occlusion. The diameter of the internal carotid artery is smaller than the diameter of the ipsilateral external
carotid artery and on the second picture on the right you can see dilution of the intracranial contrast ipsilateral to the near total occlusion from contrast that arrives from the contralateral side. Analysis of pooled data from randomized controlled trials for symptomatic carotid patients was performed
by Rothwell and published in Lancet 2003. Pooled data from ECST, NASCET and Veteran Administrations trial were analyzed. Pre-randomization of carotid angiograms from ECST study were re-measured by methods used by the other two trials. 6092 patients were included,
with 35 patient-years of followup. There was a non-significant trend towards benefit from surgery in patients with near occlusion at two years follow up and the P-value here was 0.19. But no benefit at five years. The absolute risk reduction I draw your attention,
was minus 1.7% and look at the graphs here with the thick line we denote the surgical-treated patients and thin line, medical treatment. You see the lines are identical for all outcomes measured.
Any stroke or operative death, ipsilateral stroke and any operative stroke or operative death, disabling or fatal ipsilateral, ischemic, or operative stroke and operative death. The lower risk for cerebrovascular events in patients with near total occlusion
is probably related to the presence of a good collateral circulation. And you can see in this study that that shows that as the degree of internal carotid artery stenosis increases, so is the collateral circulation with the best collateral circulation on patients who have
near total occlusion. For patients who are symptomatic and they have 70-99% stenosis, the collateral circulation protects both the medical and the surgical group. And the risk reduction is more than 50% with the green color would denote patients
who had good collateral circulation. Yellow, patients who have poor collateral circulation. And that applies for all outcome measures that were investigated, such as disabling or fatal stroke, any stroke, and TIA. Ladies and gentlemen, best medical treatment has
vastly improved over the last years and the risk of stroke and death has declined. Therefore, the benefit of the conservative treatment for near total occlusion shown on historical trials performed more than 20 years ago is likely to be much greater today.
And this is a graph from one of the publications from Professor Naylor, that shows a dramatic decrease of the ipsilateral risk of annual stroke on patients with symptomatic carotid stenosis. In conclusion, Mr. Chairman, ladies and gentlemen, patients with near total occlusion are distinct
from patients with 70-99% stenosis and have a lower risk of stroke on medical treatment. There is no level one evidence to support that a carotid endarterectomy is beneficial for this group of patients. Thank you.
- Chairwoman, Chairman, dear colleagues. I've no financial disclosures related to this talk. As you have heard already, the recommendation number 39 in the recently published ESVS
and ESC guideline on carotid disease tells you that CEA or stenting is not recommended in symptomatic patients with a chronic internal carotid near occlusion. It's a strong recommendation against the level of evidence
is however all we see. And actually, this is based, and George mentioned that already, this recommendation is based on a pooled data analysis from the ECST and the NASCET data
published 15 years ago by Peter Rothwell and the PIs of the major trials. And as George already mentioned, that there was a trend towards benefit from surgery after two years, but not after five years,
and the ITT analysis, however, might have underestimated the benefit of surgery for patients with near occlusions, because of the high rate of CEA during followup in the best medical treatment group,
and I'll come back to that later. There's a plethora of synonyms for near occlusions. Currently, the accepted that carotid near occlusion has to be defined as a distal luminal collapse of the ICA
beyond a tight stenosis. We have to differentiate between a lumen collapse, or a synonym, a string sign, has been seen here, and patients with a collapsed,
partly collapsed distal ICA, as in this example, and this again has to be differentiated from a very tight cyanosis. So let's have a look in the literature about natural history data
of near occlusion of the internal carotid artery. This is a paper from 2010 from a Serbian group, a prospective registry of 250 patients who were operated on,
and 50 patients who refused surgery for their near total occluded carotid artery. And after 12 months, the TIA rate was five versus 24%, and the stroke rate was 1.5 versus 14%, in favor of surgery,
and in addition, more than a third of the patients with a near total occlusion had progressed to a total occlusion. Another paper more recently published in 2015 from a Swedish group,
again, a prospective registry, looked at the natural history within only 90 days, and they found a very high risk of stroke occurrence in patients with a full collapse,
and the numbers were 43%, so they concluded that surgery could be considered for these patients. And more recently, from last year, a Spanish registry included also
83 medically treated patients with carotid near occlusion, and they concluded that patients with symptomatic near occlusion seemed to have an increased risk of 10.6% within 90 days
to suffer a secondary stroke. So, how are the results of stenting in surgery? Meta-analysis published a couple of years ago from a Greek group, and they also found that the stroke incidence rates
in the conservatively treated groups with a near occlusion was significantly higher than the interventional groups. So why do the pooled data from ECST and NASCET differ so much? We have to take a look
in the original papers. This is the paper from 2005, from Michael Fox and Peter Rothwell, and these are the NASCET data. This is the line of the surgical treated patients.
After three years, the rate of ipsilateral stroke was a little bit more than 10%. Best medical treatment, 18%, and if you look only at the patients who stayed on medical treatment,
the rate was more than 27%. In contrast, no such effect was detectable in the ECST trial, so why is that? We have to realize that only 16 patients in that sub group analysis
had a near occlusion with a full lumen collapse, 14 of them in NASCET. Patient selection, and more likely also the uncertainly principle in ECST
played a role in that. The carotid near occlusion data were analyzed post-hoc, statistically completely underpowered. Lower prevalence of old age, diabetes, and other risk factors in ECST,
and most importantly, more than 30% of the best medical treat arm received surgery during followup. So the ITT analysis might have underestimated the benefit of CEA. And even more important,
more than 50% of the patients with carotid near occlusion were randomized after four weeks after the index event, so recurrent events may have take place before. So the strong recommendation against surgery and CAS is invalid
from my point of view. There is lack of level one evidence for surgery and stenting, but also for best medical treatment. Natural history indicate a significant early and late stroke risk,
and some, if not all, symptomatic patients with a string sign need invasive treatment. George debated that issue in January in Paris already, and was a tact that I think that
should take place today also. Thank you very much.
- So my academic work has been funded only by independent grants and family subsidies. Firstly, endarterectomy. The only subgroup of patients with asymptomatic carotid stenosis to benefit from endarterectomy in randomized trials were average surgical risk men,
aged less than 75 to 80, with at least 60% stenosis. And they also had to satisfy a number of other criteria to fit within this group that had an overall benefit from endarterectomy. So why do we operate on so many other subgroups of asymptomatic patients as well
in the absence of any evidence of benefit? When it comes to trans-femoral or trans-aortic CAS, well, this is out as a routine practice procedure, because it causes about twice as many strokes or deaths as endarterectomy
within the peri-procedural period, and that excess risk is also measurable, carries over to the long run. And that excess risk of stroke with stenting is not compensated by the 30-day risk of peri-procedural clinically defined heart attack. This is a list of all the randomized trials
of endarterectomy versus stenting, where the 30-day rate of stroke and the 30-day rate of clinically defined heart attack was published. It involves both symptomatic and asymptomatic patients. And overall, stenting was associated with 1.6 times more strokes, clinically defined
heart attacks, or deaths compared to endarterectomy. This doesn't look good. Plus, we know that these procedures, the outcomes in routine practice are often worse than in trials. This has been shown in multiple registries,
including this meta-analysis of registries from Munster et al., showing that it took years for the average 30-day rate of stroke or death in routine practice for endarterectomy in asymptomatic patients to catch up with ACAS. And even worse, the ACAS procedural standards
have been increasingly outdated and excessive since they were published in 1995. What about TCAR? As far as I can tell, it's only being assessed in registries, and compared only with endarterectomy or trans-aortic CAS.
So with this investigational approach, we're not going to establish that it has a procedural benefit over current best medical treatment. So again, another procedure that has no established proven role in routine practice. So there's no evidence of procedural benefit
for any subgroup of asymptomatic patients anymore, due to improvements in medical revascularization. So the average annual ipsilateral stroke rate in the best-quality prospective studies now comes down to about 0.08% per year. This is 56% lower than ACAS patients
who just had medical treatment, and it's lower than patients that had stenting or endarterectomy in CREST1. At most, only about 4% of persons with asymptomatic carotid stenosis will now have a stroke caused by the lesion during their lifetime.
This is based on the observation that the average annual ipsilateral stroke rate is now 0.08%, and I'm sure we can do better than that with medical treatment alone. The average age of diagnosing the lesion is 70. The average survival after that is 10 years.
This is from past studies of this condition. About half the strokes occurring in the distribution of the lesion are not due to the stenosis. And this 4% figure also assumes a 30-day procedural stroke or death rate of zero, which is not possible all the time.
4% is not many, and keep that figure in mind. None of these should have routine endarterectomy, and certainly not stenting, until we know who this 4% are. This also includes protecting the elderly and the frail from these procedures, who have unacceptably high 30-day stroke and death rates.
Risk stratification of asymptomatic carotid stenosis is currently unable to identify those likely to benefit from endarterectomy, despite what some say. The European Society for Vascular Surgery published a guideline last year giving endorsements for endarterectomy or stenting for the average
surgical risk person with 50-99% asymptomatic carotid stenosis if at least one of these characteristics or other undefined features existed. But we know that all of these in isolation are inadequate. They lack sufficient specificity, being very common, usually much over 4%
of the asymptomatic population, with average annual ipsilateral stroke rates low. Even lower, we would expect, with current medical treatment. We shouldn't use these criteria to select patients for surgery. Combined markers are better.
No risk stratification studies have been done with current best medical treatment, and none of these markers have been established in trials. It's very important to reduce waste in any health service. This particularly applies to the Americans, it seems, because they have the highest
expenditure per person on health services, but the lowest average life expectancy compared to other developed countries. So stopping inappropriate procedures on the carotid is very important, will save lots of money and lots of lives.
After all, it is an industry built on waste and accumulating misconceptions. Thank you.
- Thank you, thank you, Dr. Veith for the kind invitation. I have no disclosures. While we continue to hear the argument that today asymptomatic carotid disease is no different from diabetes mellitus, a medically manageable disease in all, or almost all, of those patients with no role for surgery. And the rational for this argument
is quite logical and I agree with it. Today we have far better medical therapy than what was available when the ACAS and ACST trials were conducted, especially STATIN medications. And it argued, that if the medically managed patients in those trials
had received contemporary medical therapy there would have been no benefit for surgery. What they don't factor in is that the fact that today the outcome of carotid endarterectomy is dramatically better than what was observed in those trials. If you just look at the CREST trial,
nearly 1,200 asymptomatic patients undergoing endarterectomy with a perioperative stroke and death rate less than 1/2 of what was observed in ACAS and ACST, and that was all surgeons, among vascular surgeons, the stroke and death rate was about 1%. Now while these were highly selected surgeons,
these results reflect what's going on in community practice in the United States today as documented in multiple population based studies, and ironically, I would argue that this improved surgical outcome to a large degree reflects the same improvements in medical management.
We looked at the influence of STATINS in series of nearly 1,600 patients undergoing carotid endarterectomy and through multivariable analysis, showed that STATINS were associated with a 3-Fold reduced risk of stroke
and a 5-Fold reduced risk of morality. So I don't think you can so merely throw out Level I evidence from well conducted trials because you assume the medical patients would have done better if they had gotten different medical therapy, because clearly the surgical patients
would have done dramatically better as well. And you don't need to assume anything, we have real world data. This is a series of 115 asymptomatic patients with a greater than 70% stenosis at the Mass. General Manage Medically.
86% are on STATINS, 79% on STATINS and Asprin followed for a mean of a little over five years. 31 patients suffered ischemic neurological events 3/4 within the first year, nearly 1/2 were strokes, and as you can see,
there was no difference in the stroke incidents among patient who were or were not on STATINS. And the one year stroke rate was not .8%, it was nearly 20%. The second point to keep in mind is that when asymptomatic patients become symptomatic, the overhauling majority have a stroke as the first symptom.
That is, it is a tiny minority of asymptomatic patients who've suffered a stroke, who actually suffered a recognized TIA before that stroke occurred. Now I was asked to also address this issue in the elderly, and I think an epidemic prob. We're going to face with
the growth of the elderly population moving forward is cognitive impairment. If you actually test people, a quarter of individuals over the age of 65, 2/3 of those over 85 suffer cognitive disfunction. And while it's not the only etiology, we're learning that silent strokes
are an increasingly important etiology. As the neurologists pointed out in this editorial in the journal, Stroke, silent strokes occur five times as often as clinical strokes, and they affect thinking. So our asymptomatic patients may look great,
and we may think we are winning with medical therapy, but if they are experiencing microemboli, we're sowing the seed for trouble down the line. It was pointed out, even the Europeans who have been fairly conservative in this issue, have identified an number of clinical and plaque morphologic
features which identify patients they believe should be considered for endarterectomy. I certainly agree we need to be selective. I was specifically asked to address the issue of whether the percentage of asymptomatic patients who need surgery is at least 20% percent, and it clearly is.
And to support that position, I'm going to borrow from the data Dr. Abbott herself has published. With colleagues, they looked at 1,100 patients with asymptomatic at least 50% stenosis and identified clinical and plaque morphologic features, upon which they developed a risk profile.
And as you can see, while there may be some patients who had an annual stroke risk of .8%, there were many patients who had a two to three to four to five percent annual stroke risk, her own data. How man were those patients?
Those are the patients who could benefit from endarterectomy. How many? Well out of the 1,100 patients there were 923 with at least a 70% stenosis, 142 of them had a two to four percent annual stroke risk, and 84 had a greater than 4% annual stroke risk.
If you assume a perioperative stroke and death rate of 1 1/2 percent for endarterectomy, those 226 patients would have benefited from endarterectomy. My math said 226 divided by 923, at least 25%, clearly exceeding that 20% threshold. So in closing, I would simply share with you
the words of Dr. Abbott herself, who has said in her own paper: surgery may be clearly preferable for some patients if we could identify the patients at risk. Essentially, agreeing with my position in this debate. Dr. Abbott, thank you for your support.
We clearly when we see a patient who's got a bad plaque, and I would argue a patient like this is better served by endarterectomy and STATINS rather than STATINS alone. Thank you for your attention. (applause)
- I would like to thank Dr. Veith for inviting us again to this meeting and for giving the opportunity to participate in his mega debate. I have no conflicts of interest. Now, as we heard before from Dr. Abbott, which is stop operating on asymptomatic patients, and because of advancements in the best medical treatment,
stroke rates are currently way, way lower. Well, let's see about that. Now I'm sure many of you will be familiar with this slide. It is from an editorial published in 2011 circulation showing that because of reductions in smoking, there has been a parallel reductions
in abdominal aortic aneurysm-related deaths in the last few years. Let's see about strokes. We see this paper reporting that in 1998, there were 770,000 strokes in the United States. There were also 11 million silent strokes,
but I'll get to that later. So 20 years later, in 2016, we'll see that the number of strokes is 795,000, so apparently, the best medical treatment has not reduced the number of strokes, and about 610,000 of these were first and new strokes.
We have this paper from the Netherlands showing that over 10 years, there has been a massive improvement in atherosclerotic plaque composition. However, this did not translate in the reduction of strokes in TAAs. What has actually happened is that the same strokes occur
just a bit later, so there's a shift towards the right. So best medical treatment actually delays the strokes, but they actually occur as well. And of course, we have the 2017 ESVS guidelines showing that in Europe, there are about 1.4 million strokes annually,
causing about 1.1 million deaths, and that's the most important thing, actually, that overall, about 10 to 15% of all strokes follow thromboembolism from a previously asymptomatic internal carotid artery stenosis greater than 50%.
So it may be, actually, that in randomized control trials, there's been a reduction of strokes, but in reality, patients are not happy to go ahead with the best medical treatment and they want an intervention. That's why SPACE-2 was terminated.
Now do we have proof that best medical treatment alone is not adequate for all patients? Yes, we do. This is a study from Boston. It was shown again earlier, and it shows, well, 918 medical retirees follow up for 3.6 years.
Plaque progression occurred in 262 carotid arteries, and 13.7% of those developed symptoms. We also have an independent study where, actually, Dr. Abbott was co-author of the ACSRS. Again, 1100 patients, follow-up four years, and 130 ipsilateral cerebral or retinal ischemic events.
That's about 40% again as well, so the same percent. So in fact, medical treatment alone is not adequate for stroke prevention in all asymptomatic patients. Not all patients carry the same stroke risk, so one-size-fits-all approach was not really recommended. And are there ways to identify which patients
will benefit from intervention? Yes, there are, and these are summarized in the review article we published a couple of years ago. And we can see that the ESVS guidelines suggest that patients with asymptomatic 60 to 99% stenosis with one or more imaging characteristics
and a reasonable life expectancy should be considered for a prophylactic carotid intervention so that they do not become asymptomatic, and this is a list of all these characteristics, including transcranial Doppler-detected emboli or intraplaque hemorrhage or MR and others,
and as we support in the commentary we published last month in JVS, there is a need to identify risk factors and appropriate stroke risk education models to selectively guide carotid intervention procedures. All of them should get best medical treatment, obviously, but some of them would benefit
from a prophylactic carotid endarterectomy. So in conclusion, ladies and gentlemen, BMT alone is not adequate for all asymptomatic patients. Stroke rates have not decreased despite vast improvements in PMT. That includes registries, not just randomized control trials
where everything is strictly supervised, and as the guidelines say, 10 to 15% of strokes occur as a result of thromboembolism from previously asymptomatic internal carotid artery stenosis. Plus there is the silent strokes that we,
that talked before. So a patient, for example, suffering a TIA in his sleep will still be considered as asymptomatic the next day, and thus, obviously, not good. To be honest, I'm not sure what's the value of such a debate since we have the guidelines
and they clearly recommend an intervention for some asymptomatic patients, and I think this percentage is close to 10%. Thank you very much for your attention.
- Thank you very much for bringing me back Frank, to this wonderful meeting and this great debate. Unfortunately half of my slides have been shown already so I'll try to say some different words on the same themes and maybe emphasize a few things. Stroke risk is declining in patients with asymptomatic disease
I don't think anybody can debate that, even though someone just tried. But I think you should take a look at this paper from Kansas from last year where they follow 864 patients with asymptomatic carotid disease
for I think up to six years. And this little bit complex slide shows on the Y axis with blue, the cumulative risk of stroke, TIA, and carotid revasc in different groups with different levels of compliance to medical therapy.
So those you don't want to treat with medical therapy and you wish to operate on the far left, they carry a 3.5% risk of stroke. Whereas those where you treat them appropriately on the right side, and notice they don't smoke, their blood pressure's under control,
LDL is low, and they're on statins, their combined stroke, TIA, and revasc risk is 0.7% combined 0.7%. And similarly in the bioimage study where we followed 6000 patients who were all asymptomatic from any cardiovascular disease
for up to three years. We identified 349 at baseline with an asymptomatic rate and 50% stenosis. And after three years that group experienced four strokes, an annual stroke rate of 0.4%.
And this is in Americans, not Europeans. So my interpretation is that the risk of TIA, stroke, and revasc becomes extremely low if risk factors are treated appropriately. And progression of stenosis is a sign of
insufficient risk factor control and preventive treatment rather than a sign of increased risk of stroke. Yes, we have new guidelines and yes in January we published the European guidelines as you already had heard.
And we did write but rather than having a class 1A recommendation for surgery in asymptomatic patients, it's a 2A provided that there is at least one or more imaging characteristics associated with an increased risk and a documented lower than 3% risk
of a perioperative stroke. And similarly for CAS but it's a 2B and not a 2A. And the reason for that distinction was this small meta analysis that is also published in the same document, which favors endarterectoma for asymptomatic stenosis.
And if you look at this complex sheet you can see that if you're on the asymptomatic which is the blue side here, and that you have more than one feature you can go on maybe to an intervention. And some of these data comes from this review paper
that was done with our German here. And you can see that in these papers we found an acute annual rate of ipsilateral stroke which was, you know, 3, 4, 5, or 6% however this is the good old story, these data were obtained at a time when patients
were not treated as well as they are today. So we can still discuss whether or not this is useful. So for asymptomatic carotid stenosis the risk is very, very low of stroke, 0.3 to 0.5% per year on average. But there's a very high risk of cardiovascular events
which is probably more important. Therefore, medical management works and it lowers risk. Endarterectomy while stenting is in general not warranted unless this high plaque can be identified. And that's where we need 3D ultrasound
because as it's asked in my last question, how do we identify them? And using 3D ultrasound, we can do tomography, just like we can do with CT or MRI. The difference is that this is cheap, it's going to be available everywhere, which MRI is not.
And MRI is not simple. And using this methodology to define where the plaque is and where the center is, we were able to show a fantastic reproducibility of a plaque volume assessment in 37 plaque scans by blinded investigators.
And this will allow for much better plaque quantification of volume and morphology. Assessment of degree of stenosis will improve because we'll now be able to do the angle compensation in 3D. The examination will be speeded up
and it's going to be easier to perform a good scan. So we have all the opportunities we need to get new, good, valid data. Thank you for your attention.
- Thank you. It's a great pleasure for me to be back here in New York and talk to you on the subject and I'd like to thank Dr. Veith for the invitation. These are my disclosures. We're going to start by some images. This is a small plaque that did not change
over three year period with intensive Statin therapy. But this is another plaque that traveled in area and producing nearly 50% stenosis in a patient that was not taking Statins. And here is a large hypoechoic plaque producing 80% stenosis
and three years later, three month later despite in the presence of intensive Statin therapy we have some echoes in the lumen in the plaque suggesting that the position of collagen but the plaque produced 90% stenosis in a 54 year old man who ended up having carotid endarterectomy.
Now let's go to some data. Future belongs to volume measurements as said by Dr. Sillesen and very early it has been shown by Dr. David Spencer's team in Canada that if you measure plaque volume, Atorvastatin 80 mg will reduce the plaque volume.
Something that will not happen if you are with placebo. Also, the inflammation can be reduced by Statins and this has shown by studies randomized were measuring the uptake or radio active glucose in the plaque and here you can show that the diet, on the top had no effect in the inflammation in the plaque.
On the other hand, Simvastatin make the radio activity in the plaque and inflammation reduce. And here is the data showing a reduction in the Simvastatin group while there is no reduction in the inflammation in the diet group. In 2010, we looked into the literature
on the effect of statins on plaque morphology and we found 17 prospective randomized control trials and we found that there was increase in echogenicity of the plaque in nine, a decrease lipid core size in nine, regression or slow progression in seven
and reduction in microemboli in one. And the above effects correlated with the decrease in LDL rather than the intensity of therapy. We know also that at 50% reduction in LDL is associated with 50% reduction in ischemic stroke. Now, in more recently, we have learn from The FOURIER Trial
that when Evolocumab is combined with Statin and Ezetimibe and LDL goes down to 30, there was an additional 25% reduction in ischemic stroke and also when you did IVUS in the coronary arteries there was a reduction in the coronary plaque volume. Now, we come to the Omega-3 story.
About in 2003, there was a landmark publication in The Lancet, in a randomized control trial where it was shown that 30 days of Omega-3 would reduce the inflammation and produce plaques with thicker fibrous caps. I like to point out at that time,
only 33% of the patient were on statins. The same group from Southampton, nearly 10 years later repeated this study and they showed that there was no difference between placebo and treatment groups. But I'd like to point out at that time, 85% of the patients were on Statins.
Now, we know from by looking at the early systematic reviews based on papers before 2000, that there was about 20% reduction in mortality in myocardial infarction mortality. But if we look at the most recent systematic reviews and meta-analyses,
based on papers published after 2002, we find that there is little or no effect on mortality or cardiovascular risk and these patients have been on Statins and a lot of them on other good Statin therapy. The conclusion is that Statin treatment
to target of LDL less than 70 stabilizes plaques and reduces embolic phenomena including stroke. Lowering LDL below 50 mg stops plaque progression and is often associated with plaque regression. And diets high in Omega-3 may be beneficial
in healthy populations not on statins. However, Omega-3 Supplements have no additional effect on atherosclerotic plaques and no benefit on cardiovascular events in patients on modern statin therapy. Statin is so effective that there is no room for improvement.
Thank you very much.
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