Originally Broadcast Wednesday, April 28
A case-based overview of contemporary treatment approaches in stable coronary artery disease.
Drs. Sripal Bangalore, Usman Baber, and Darshan Doshi discuss a case-based overview of the latest treatment approaches for stable coronary artery disease. They break down how to maximize guideline directed medical therapy, what’s evolved over time regarding appropriate use criteria, and what impact clinical trials (including ISCHEMIA) should (and should not) have on your practice. They also cover special scenarios where comorbidities, like advanced renal dysfunction or diabetes, may impact treatment decisions.
Mhm. Welcome to the next installation of the bio merge educational series where we will be discussing stable ischemic heart disease. I'm sure she does, she and I'm an interventional cardiologist at the massachusetts General Hospital where I helped direct the complex PC program. I'm thrilled to be joined by a doctor. Sri paul dangler and Usman Babar, Both of whom are exceptionally well known within the international community, but for the 0.001 of you that don't know that. Let me introduce them formally. So Dr Sri Paul Bangle or is the director of interventional cardiology as well as complex coronary interventions at the Bellevue Hospital. He's also the director of tap lab research and cardiovascular outcomes at N. Y. U. And go home. Um Guzman Barber is the director of the Cath lab as well as the director of the international cardiology Fellowship at the University of Oklahoma. Uh We're excited to have both today. Now we anticipate that tonight's session will be a lively one with each of us. I imagine having various varying views on the state of affairs regarding the clinical trials and studies for the management of stable ischemic heart disease, the appropriate use criteria for Pc. I. And the practical management of patients with the stable ischemic heart disease. So with that stated, let's get started with one of the main investigators of the ischemia trial, who will be discussing some of the seminal clinical trials for stable ischemic heart disease treat ball taken away. Thank you there. I think this is uh this is it's great to be on this particular session. So I'm going to kick this off by discussing some of the revascularization decision and chronic coronary disease. Uh these are some of my disclosures as it relates to this particular talk, but the key thing I want to emphasize is today we're going to discuss about chronic coronary syndromes. So I I don't think we should be extrapolating this too uh even remotely to a patient with acute coronary syndromes. Um First of all, so if you have a patient of chronic only uh disease stable ischemic heart disease, however you want to term that there are a number of treatment options for these group of patients. And one is uh medical therapy guideline Director of Medical therapy, optimal medical therapy, Pc. I. And cabbage and other options. And it's critically important to remember what we are targeting with each of these therapies for example with optimal medical therapy were not only targeting significant stenosis, significant stenosis as we uh define as uh 70% of greater stenosis. Um but we are also targeting and all of the non significant lesions which can potentially be vulnerable plaques and which can potentially rupture and cause an M. I. With cabbage cabbage bypasses the 1st 50 of a coronary tree. So it it targets significant stenosis but also it does target some of the non significant lesions within the 1st 15 where it is bypassed. But as A P. C. I. Is pretty much target significant stenosis. And so although these are the potential treatment options, there are trade offs that we have to be aware of. Um medical therapy has its own side effects. And of course there is patient compliance associated with it, cabbage is invasive and although P. C. I. Is also invasive, it is minimally show. But these are the trade offs that that needs to be considered when we are making decisions about uh management of these patients. So let's dive right into the schema trial. So I kind of briefly summarized the design and what was done in the trial and of course it took us 10 years. But let's see if this one slide can capture all of the things we did. So in the schema trial, we randomised 5179 patients to an investor strategy that started with cat and then based on the findings on cornea geography. They were they're either under when PC I cabbage or a medical therapy alone or the patients were randomized to a conservative strategy which started uh with the medical therapy alone with cat and revascularization preserved for patients who failed medical therapy. So if you compare this with all of the prior strategy trials, that this is the largest treatment strategies trial and the question at the after we are done with the trial, did we really enroll a high risk subgroup of patients? So we set out to enroll patients who had at least moderate are severe ischemia. And at the end of the trial, 54% of all the patients who were randomized that severe ischemia, 76 of patients were randomised as multi vessel coronary artery disease, with nearly half of them approximately lady disease and coronary CT angiography. In patients who are uh in terms of Catherine revascularization. In the trial. In patients were randomized to invasive strategy, 80% of them got revascularization, 74% of those were through PC. I. And 26% of cabbage. So I think this is critically important to recognize that ischemia was not a trial of P. C. I. So we had 26 of patients that want to rent cabbage In the conservative strategy. At the end of four years, 28 of them are on went cat and 23 underwent revascularization. Medical therapy is also important to highlight it was used equally between both treatment groups, 95% were on statins. In fact, two thirds of them were on a high intensity statin. The LDL attained at the end of the treatment was uh 64 mg per day. S leader And the the mean systolic blood pressure at the end of the trial was around 129 mm of Mercury. So let's look at some of the results and uh you know, some of the potential reasons to consider revascularization in patients who have stable coronary artery disease. Um one of the things is to potentially improve survival. So are their data to support improvement of survival in patients with stable coronary artery disease. So these are the results from the Ski Mia trial and also the scheme, you see Katie trial where we enroll patients with Geo far less than 30 our analysis. So for the endpoint of uh all cause mortality, we see, we see that the invasive versus conservative strategy really did not make a difference in the scheme trial. So we did not really show that invasive strategy improves survival either in the ischemia trial or in the scheme. You see Katie trial. So if you were to look at now all of the trials of revascularization was this medical therapy in stable colonial to disease. This is a matter analysis of randomized trials. Looking at the end point of all cause mortality. And again, we see that the results are very consistent with what we found in the Schema trial. No significant improvement and survival with the routine revascularization strategy when compared to medical therapy, whether these were back in the day, knows 10 trials or stand trials. So in terms of potential reasons to uh revascularization, stable coronary artery disease randomized trials have failed to show an improvement in survival compared with the medical therapy alone in patients with stable coronary artery disease without left main disease and largely preserved ejection fraction. Uh What about the other goal of two to prevent other cardiovascular events? Uh These are findings from the schema trials and the schema trial invasive strategy was associated with significant increase in the risk of procedural M. I. But what we found was that there was a significant decrease in spontaneous and my 33 reduction in spontaneous and my with invasive strategy when compared to conservative strategy. So if you look at overall my in the Eskimo trial, it was awash between given the fact that the procedural mes were increased and spontaneous. Mes were already used. Um So everybody organization or invasive strategy reduces spontaneous semi but increases procedural AM I. And if you look at all of the trials of revascularization, was this medical therapy? The findings are largely similar. No difference in overall Emmy but increases procedural me, significant decrease in spontaneous and me. There's also decrease in unstable angina with revascularization when compared to medical therapy. So to going back to the drawing board revascularization for a patient with stable ischemic heart disease. Uh data does support a reduction in spontaneous semi and unstable angina with an invasive strategy uh mainly with revascularization. I think one of the other fundamental reasons to consider revascularization um In in our patient is potentially to improve quality of life. Um These are again findings from the ischemia trial at the red lines are for invasive strategy. Blue is for conservative strategy. What we showed in the ischemia trial is a significant implement and and gender related quality of life. Um A bit an invasive strategy when compared to conservative strategy. And this benefit was actually durable, up to four years of follow up. And just to quickly go back to courage and barry to d encourage and barry to d a similar findings were seen. But the benefit of invasive strategy uh specifically with PC I was kind of uh limited. For example, in the courage trial. After three years, there was no significant difference for angina relief between PC. I. And medical therapy. And in Bari two D. Uh in the Pcs stratum, there was no significant difference in angina relief after one year between PC I. And medical therapy. The difference in ischemia is that we see that the music strategy as a durable relief and general relief or the duration of follow up. But what we also saw in the Schema trial was the probability of no engineer really dependent on baseline engineer frequency. So if you have a patient with daily or weekly engineer, for example, a sack score of 50 invasive strategy was associated with significant improvement and uh increasing probability of no engineer. You only needed to treat three patients with an invasive strategy to have a significant benefit of reducing angina in this group of patients. And of course, if you have a patient who had no engineered baseline invasive strategy does not make a patient who has no symptoms to feel better. And this was not only seen three months, but also 12 and 36 months of follow up. So does revascularization improve quality of life. But yes it does. But of course not in the asymptomatic patients. So let's move on. So now, as we have seen data for revascularization versus medical therapy, if you have now decided on patient needs a revascularization, how do we best choose between PC I. And cabbage? Specifically, if the patient has multi vessel coronary artery disease, We did describe about um the benefits and the kind of pitfalls of cabbage was this PC I, what do randomized trial? Tell us about the PC. I was this cabbage for multi vessel colonial to disease. So the potential advantage of cabbage tends to be long term. So the clinical trials of cabbage was this PC. I show that cabbage um in most clinical trials have shown that cabbage reduces the risk of repeat revascularization when compared to PC. I. In a few trials, cab business has been shown to reduce the risk of M. I. When compared to PC. And some of these trials are highlighted here and in uh even fewer trials, cabbage has been shown to reduce the risk of death. And specifically, this has been shown in the Freedom Trial and also in the Excel trial. The disadvantage of cabbage of course is all short term when compared with PC. I cabbage as an increased risk of very procedural events. And all of these are kind of listed here, including a significant increase in death and my stroke and renal failure. And prolonged recovery time is a disadvantage with cabbage. So how do we look at the data for cabbage versus P. C. I. And you know, so there have been a number of clinical trials but many of them have used outdated PC. I technology. But when you compare cabbage with the newer generation drug eluting stents, we publish some of this data from the new york state angioplasty registry, looking at patients with multi vessel disease, asking the question, um, what about PC I with a bromance? Eluting stent was just cabbage. This is data from 18,000 propensities called match patients. And if you look at the primary outcome Victoza, all cause mortality. We did not see any significant difference in the death between cabbage and PC. I, cabbage was associated with significant increase in the risk of stroke when compared to PC I. And this has also been shown in a number of randomized clinical trials. And if you look at the end point of myocardial infarction, cabbage at a lower rate of myocardial infarction when compared to PC I. But the effect of effect on am I really dependent on completely disapprove. Ask if there was complete revascularization with PC I. There was no significant difference between PC and cabbage, but if there was incomplete, we've asked, Pc I, cabbage was associated with lower risk of M. I. When compared to PC. I. But the take home here is that we did not observe a mortality benefit of cabbage in the new york state angioplasty registry. So the data I showed is from a registry. What about randomized trials? So this is a meta analysis of randomized trials of cabbage comparing it to second generation D. S. And for short term outcomes. So we see that P. T. I. Is also stated with 34% reduction in maize and you can see all of these components when compared to cabbage. This is a 30 days. But if you look at longer term outcomes, I mean, even though the maze and point tends to favor cabbage, there is no significant difference between PC and cabbage for death or other endpoints between cabbage and PC. I with the newer generation Ds. So in other words, both the data from observation studies and a randomized trial seems to go hand in hand suggesting that no significant mortality benefit of cabbage. What about the subgroup of patients with diabetes? Um, we looked at this in the new york state angioplasty registry, looking at all cause mortality. Again, no significant difference in survival between PC and cabbage with new generation stands for all cards mortality. Am I again tended to favor cabbage, but in the subgroup of patients who had completely revascularization with PC. I, there was no increase in M. I with PC. I. When compared to cabbage strokes. Again, favored PC. I lower stroke with PC. I than cabbage and repeat revascularization, just like in every study favored cabbage, lower risk of the repeat revascularization. But again, no mortality benefit of cabbage. In the diabetic subgroup in the new york state angioplasty registry. What about data from randomized trials? This is data from freedom. Follow on trial. Um, of note, only half of the randomized patients in freedom were followed longer term. And at eight years there was a significant reduction in mortality by people with cabbage when compared to PC. I in the um in the freedom trial. So cabbage led to lower mortality than PC I. So interestingly, this is not true for all the randomized trial. So if you look at this in taxes, this is data from the syntax trial for up to 10 years of follow up. There is actually no significant difference in mortality between PC. I. And and cabbage, even though both these trials used first generation D. S. Um and in fact in the syntax trial, if you look at the 10 years data and mortality and I break it down by diabetes versus no diabetes. Again, we don't see a significant heterogeneity of treatment effect, no significant difference, no benefit of uh reduction in mortality with cabbage and compared to PCI. Um so, uh if you just resume that there is a mortality benefit of cabbage or pC I should this be a compelling reason to choose cabbage in these group of patients, there are trials, as I pointed out before, that shows a potential mortality benefit. And of course, there are other trials. We do not show mortality benefit of cabbage when compared to PC I. So the real question is, uh what is the extension of survival at eight years in the freedom trial? Because the patients really want to know, okay, if I choose one versus the other, I don't want to know how many patients will survive at the end of it. I want to know the extension of survival. We did the back of the envelope calculation in the freedom trial to see what is the extension of survival by cabbage when compared to PC. I in the diabetic subgroup. And at eight years, the extension of survival is only three months if you choose P. A cabbage vs. PC. I in this trial. And what do patients perceive of longevity benefit? Uh so this is an interesting study where patients were asked. Uh you know, I'll give you an extension our survival. There will be an inconvenience of doing something. How much extension of survival do you really need to offset? For example, in this case, uh inconvenience of taking daily medication. Interestingly here in this particular, studied patients wanted at 12 month extension of survival. So for the majority of patients, a survival benefit longer than at least six months is needed to offset even the inconvenience of daily medication, let alone cabbage. So it kind of provides you with a different perspective of what patients really want and talking about patients versus physician perception. This is a survey of around 7 85 cardiovascular patients and clinical trial is to to understand what a clinical trial is rate as very important. And of course we as clinical trial as we always will say, oh, death is the ultimate end point. And we are generally tend to rank that the far greater than stroke. But if you ask a patient in this particular survey analysis patients actually reiterated stroke to be as important that even more important than that. So this kind of uh emphasizes the need to personalized patient decision and it's critically important to uh, you know, patient preference really matters in terms of uh their own perception of uh extension of survival was just the risk of stroke from each of these procedures. Um, just to conclude, So if you look at the data for co chronic coronary syndromes, a routine revascularization was just the initial medical therapy. So if you chose the strategy of initial medical therapy, one in three based on randomized trials, will undergo revascularization for 4.5 years of follow up. No no difference in survival whether you choose upfront medical therapy versus revascularization, but revascularization reduces non procedural and my unstable angina. There is also greater freedom from angina but this is at a cost of increased procedural army and choosing between PC and cabbage. Uh data from randomized trials and also many observational studies. Such a similar mortality between PC and cabbage specifically when PC is optimist and as such, the decision between PC and cabbage should be based on ability to completely revascularization. Also surveying the short term risk of death and stroke with cabbage with long term benefit of reducing the risk of repeating revascularization and the critically important uh Point is patient preference is critically important to make this decision and thank you for your attention. I'm sure we're going to discuss more about them many of this during our discussion. Alright tree ball. So I think that was a fantastic world wind. Uh review of a very complex topic. I mean I think you went over some of the salient seminal clinical trials as well as um an overview regarding revascularization strategies. So you want to stop here and spend a little bit of time doing some Q. And A. With you if you don't mind. So the first question I have for you ST paul is the fact that in ischemia what you essentially we're doing what you know the data showed is that you were exchanging peri procedural mes for spontaneous semis if you underwent an invasive route versus conservative route. So I mean not all m eyes are built the same way. I mean what are your thoughts on that? You know I have my own thoughts. I'm pretty sure this man has his own thoughts. But um you know, is there a difference between the two and what's your perspective on that? Yeah. So that's a great point. So um you know in the schema trial we had a very stringent definition of procedural am I? So you know, it wasn't just a troponin leak that would be considered as procedural, am I? It was we needed a many fold higher troponin elevation patients needed to have something else associated with it. Um as such, I mean the incidents of procedure under my is low. We recently published prognostic value of procedural with a spontaneous in mind from ischemia trial. And what we see there is that spontaneous semi seems to be more strongly associated with death compared to the procedure. Lemme I mean I think this kind of goes along with many of the data out there. Kind of similarly supporting that spontaneous and I may be critically more important but at the end of the day at four years, if you look at overall survival we still don't see a separation of those curves. So you're hoping that, I mean if this is really true spontaneous and me is a big driver for mortality, can we see it longer term? So hopefully the long term follow up of the ischemia trial should shed more light into this. Yes. I mean dovetailing is my next question. You know, certain people that have reviewed the trial. I think that the curves for the primary endpoint seems to be starting to diverge at five years and again potentially driven by spontaneous M. S. And hospitalization, find stable angina. So talk to us about your thoughts with that interpretation and the effect that the long term study will have. Yeah, absolutely. I mean, you know in this trial we saw for the primary and point um and also for CBD autonomy, The curves actually cross over and the crossing over point is uh around two year time point where up front there is a high risk with uh invasive strategy and longer term there seems to be a potential benefit. So uh we recently were awarded a grant from the NHL B. I. To continue and follow up of the schema trial. So we're going to follow the same cohort for another five years. So hopefully that should shed more light as to whether the separation of curves and specifically for mortality. Where are we going to see some divergence occurred for mortality or is it going to be uh, you know, a superimposed. So that's fantastic. I mean I just think about stitch right, which was a trial that was perceived to be a negative trial of five years. But then with the extension study after 10 years it was marketing in favor of revascularization regardless of what endpoint used. So I'm hoping that again, the extension study, which is fantastic scheme is gonna have I think is going to be very pivotal. Um so I think some of the questions that we still have remain not fully adjudicated or answered. The next question I have for you is specifically as it pertains to orbit is so one of the trials that you didn't get a chance to touch upon, you touched upon many was orbit. You know, I wanted to know your thoughts about how orbit of fit within the context of ischemia as well as courage. Yeah. So I think there are many different perceptions are influences of Arvida and in the ischemia context. I mean, we have had a number of discussion of it. I mean, what we see is the results of ischemia in orbit to in fact is very similar. Uh, what do I mean by that? I mean orbit to was a sham controlled PC. I trial. Although there was no sham group in the schema trial. The primary endpoint in orbit a was exercise time. And of course we did not test that in ischemia. But if you purely look at quality of life, the sack um, angina frequency quality of life. FX size was around 4.4 in orbit at six weeks. We're seeing something similar in the ischemia trial and in the responded analysis in the Arvida. And if you look at PC I. Versus sham uh control in in in order to 50% were angina free at six weeks and 30% in the sham control group. So in other words, PC I actually reduced the angina when compared to uh the sham control arm and orbital trial and that the effect sizes are very similar to what we see in uh ischemia trial, even though this was not blinded. Um and there was no sham group. Yes. So, I mean, again, I think you bring up some great points me one of the, I think there's many ways to interpret courage for instance. Um So, you know, let's just say an interventionist had run that study from start to finish and had actually presented the outcomes. Could this be a potential interpretation again, Guzman, please. I would love your thoughts as well. So yeah, I'll basically show that there was no difference between PC I. And optimal medical therapy but that there was symptom relief that was quicker with PC I. So essentially one could make the argument that PC I offers symptomatic relief quicker without necessarily harming the patient. Would that in your you being a reasonable interpretation of that trial? Yeah. Sorry, go ahead. No, no, it was martin. Go ahead. I've been speaking so. Yeah. No, no. I mean, I, you know, I think you know, the thoughts and the perspectives laid out comparing Robida and the schema are very well taken. I mean at the end of the day, two trials, both with medical therapy, both looking at invasive options and ultimately negative with respect to different primary endpoints, obviously very different um endpoints, but the overall theme I think is consistent and the quality of life benefit that um I think that we saw in ischemia is certainly corroborated by what we see in Arvida. But going back to, you know, one question Darshan that you had brought up um like to hear, you know, ST paul said on this as well is, you know, we see um we've seen these non A. C. S. Corporate for example corporate. And my where we see invasive therapy implantation of stents reduces and mind the setting of A. C. S. It makes sense. There's sort of this pro inflammatory state and um we can perhaps modify risk of those vulnerable plaques. But that paradigm was not supposed to be fulfilled for stable syndromes. And so why in this scheme you are we seeing a reduction spontaneous? Am I over time with the invasive arm with background medical therapy being comparable? What's the you know, that's the question that comes up when we discuss this. Um You know, I think it's a surprising finding one I didn't expect to see at all reductions in spontaneous somebody looks like the curves keep on separating. What is that? Is that because of bypasses? Can we? Uh That's also the pc ir Yeah. So that's a great question. So we are exploring more in detail but we did publish some of the results in Bernie treatments analysis in circulation. Um I mean, what we're seeing is the M. I. Signal is seen both with Pc. I. And cabbage and the fx size receive with P. C. I. Is very similar to what we see in completely trial. I mean, my take on this is, you know, this notion of vulnerable plaque um uh etcetera, that most of the plaques that rupture or less than 50% and that causes an M. I. Is from three or four decades ago. And when you look at Greg stones prospect trial, I mean, it was a combination of features, I mean, take far, but if you add tick for two ml, a less than for then at black burden and those had the highest mace. So what I suspect is if you actually medically optimize both treatment groups, the patients who do have severe lesions, specifically more plaque burden are also going to benefit from a reduction in am I if you fix that blockage? So I think that's why we're seeing a reduction spontaneous and my butt with both Pc and cabbage cabbage. Of course it makes intuitive sense. All right, So one last question and then I think we'll turn it over to Guzman. You know, you also went over the modes of revascularization during cabbage, the P. C. I. And from your presentation, it seemed as if there was almost no scenario where cabbage with superior. Are there are there particular scenarios if you do feel where it is superior or or are there other things that you think one should considerable compared to material? Yeah. So I think that the superiority is kind of a loaded question and as I was saying, like, you know, it really depends on what end point and what is it? What does it mean for a particular patient? I mean for me, the fundamental thing is if you have a patient with multi vessel disease, the fundamental question is, can you completely revascularization? And if the answer with P. C. I. Is no, you cannot completely revascularization. And if the surgical risk is not high and uh you know, I would think in that scenario cabbage is going to be superior for outcomes and whether you completely re vascular is many times maybe institutional and operator dependent. I mean, there may be centers out there where even a bifurcation is too complex for them and maybe patients are better off with cabbage. So I think it's a risk benefit discussion and I think we can come up with many different scenarios where each modality will be superior based on your end point and patient preference. I think you're right. I think ultimately comes down to the ability to perform complete rebounds. So whether it's easy or complex corner interventions, I think that if you have the skill set that potentially you can offer outcomes that are similar to the average. All right now, with that being said, let's move on to Guzman, who is going to discuss um more real world data and give us more practical figments. Mhm. Well, great, well, thank you so much. Darsha is wonderful to be with you and ST paul to have this discussion on this important topic. And so as you mentioned, what I'm going to do over the next few minutes, let's try to complement But triple has just gone through with respect to more real world evidence, contemporary trends and this issue of the appropriateness criteria. These are my disclosures. So what I'll do is I'll talk a little bit about medical therapy, revascularization trends and then finally touch on the appropriateness criteria how we may or may not use these. So just to sort of start things off, let's first kind of just define what we mean by medical therapy. And this is important is a term we use a lot but has formal criteria that is articulated both in clinical practice guidelines and think it's critical eyes of clinical trials such as the ischemia trial. And I think it's important for us to understand what this is because at the end of the day is the comparator or that are invasive approaches are up against. So we can think about medical therapy in terms of pharmacologic interventions. So certainly all patients have done an aspirin stat and all patients ideally high intensity ace inhibitors or A. R. Bs, not in all patients, but certainly the majority who have underlying comorbidities that are very prevalent in the stable ischemic heart disease, population, hypertension, renal disease and so on. The beta blockers. Not in everybody, but certainly those the prior my or reduced the f and certainly first line as an anti an journal. Now just being on these medications isn't enough. There are also goals We need to achieve those goals. And this is what was set forth in the ischemia trial, is a blood pressure less than 1, 30 by 80 LDL cholesterol less than 70 and a hemoglobin a one c less than 8%. And then of course you have lifestyle behavioural interventions or modifications that we want to achieve. A paramount. Among those are smoking cessation and getting enough physical activity at least five times per week. So again, these are the criteria that are set forth. And why are these important? Well, these are important because if we're able to achieve even a handful of these are patients are going to do quite well. This has been shown in multiple studies. These are data looking at participants in the courage trial over a very long term follow up and what they showed here is a group of patients according to the number of goals that they achieve, that. We just went through LDL cholesterol, smoking cessation, blood pressure, so on and so forth. And then here you can see the proportion who died. By the end of this follow up. And what becomes very clear in this graph is those who are not able to achieve many of these goals. 012 or three tend to do pretty uniformly poorly. Those who get to at least four or more do do very well with respect to with respect to mortality. So medical therapy works, it's very good associated with excellent long term benefit. And therefore, probably no surprise why we're seeing in trial after trial that Streetball has just gone through for us, why it's really hard to beat medical therapy. Because if you get to these threshold patients do quite well. The challenge for us from an implementation standpoint in the setting of clinical practice is how attainable are these goals? As ST paul told us, the medical therapy in ischemia was actually extraordinary. Almost everyone was on an anti platelet agent, 95% on a statin. Again, not everyone in ASIA are Air B but about 70% beta blockers and three quarters and adherence at the end of the trial was over 80%. So this is really the contemporary benchmark or standard. And if we want to try to get to the level of medical therapy that we're seeing clinical trials, this is sort of what we need to achieve which for anyone is taking care of patients with these complex comorbidities. We know this is extremely difficult and we have a lot of studies highlighting that explicit point. Again, these are data examining a pc. I registered the N C. D. R registry in the United States and what they did here is they looked at the proportion of patients who achieve optimal medical therapy that was defined in this study as a beta blocker and anti platelet agents, the statin. And they looked at the use of OMT prior to the publication of Courage in the white circles. And then after the publication of Courage and the black and what's very obvious there's really been no change number one. Number two, you can see the proportion of patients achieving OMT is barely above 40% not anywhere near the 80 plus percent we're seeing across the board uh in the ischemia trial. And what the authors highlighted this paper is that when we are choosing pcr revascularization, really, the implicit assumption, endorsed in guidelines endorsed the appropriateness criteria is that we have given OMT a real option and patients are really been tight traded their maximal doses. And so what they say here is that achievement of OMT clinical practice is clearly a challenge. Which is certainly very true Now. These data are about 10 years ago and perhaps things have changed in a more contemporary period. And these are data now not looking at a Pc I registry, but instead looking at patients in just clinical practice in the United States. These are data from the clinical registry. And you can see here, this is over about six million patients and over 700 clinical practices. And what they did in this illustration here is they plotted the proportion of patients over time. We're taking what they defined as composite medications. So, in 18 platelet A state a statin, beta blocker, ace inhibitor, or an Air B. And you can see a modest improvement in these white diamonds over time to about 38 to 40% or so, patients are actually taking at least one of these medications. What's shown in the box and whisker plots behind that, however, is the variability across practices. What can one again appreciate is that these boxes have become somewhat smaller over time, indicating less variability. Nonetheless, there are still many practices where patients are on a few of these medications as you can see here. Now again, one might argue that well, perhaps it's hard with these medications with respect to side effects, beta blockers, renal side effects. So what if we look at another class of medications such as statins? Really no controversy there, most of these are now generic and if patients don't tolerate one stat, we can usually get around that by changing the dose or the frequency of administration. So, again, data from the pinnacle registry, looking at statin use in patients with CKD. Again, looking at the white diamonds, we can see stat news has gone up nicely. So, the proportion of patients taking status based on these data in 2017 is about 80%. Again, not where we were with the ischemia trial at 95%. You can also see these boxes are getting smaller over time indicating less variability, but still, you can see there is a substantial amount of variability. Indeed, in about 25 of practices, the prevalence of statin use among those patients is below 72%. So overall we are doing better. There's still a lot of variability and away still a fair way that we need to go to get our medical therapy to the levels we're seeing in clinical trials. Now, thankfully we have more than just medical therapy. We have revascularization as well for our patients are intolerant or can't take these medications or have um, uh, symptoms despite being on medications. So, we think about coronary revascularization from a real world perspective. These are now administrative data in the United States, looking at the last 10 to 12 years or so. What you can see in the orange line is that overall uh, T. C. I. Volume has gone down. This has been shown over and over in multiple studies. Perhaps a somewhat of a plateau in here in the last couple of years, analogous lee proportion of patients getting re vast arised by bypass surgery has also declined, not as as as much and there's a lot of different reasons for this. I think the most commonly cited reasons for why there are fewer patients undergoing coronary revascularization with either PC or cabbage is the following Number one trials such as courage and the ischemia trial that are prioritizing and identifying the benefits of medical therapy, particularly with respect to endpoints such as mortality. Number two is background prevention, particularly use of statins um and then finally the appropriateness criteria. So all of these I think play a role in why we're seeing less coronary revascularization in aggregate. Um in in our patients we are also seeing important changes in the types of patients who are now coming to the cath lab for intervention. Very dramatic is the number of patients with stable syndromes that's actually going down the topic of our conversation today. The proportion of patients who are now getting PC with acute syndromes, either non S. T. Elevation syndromes or unstable angina has gone up or as stable syndromes have actually gone down. The type of patients were taking care of today with respect to both patient case mix and procedural complex has also gone up including prevalence of P. A. D. A. Fib very common challenging scenario with respect to use of anti from biotic therapy and again, something that we don't see all that often in our major clinical trials, background prevalence of stroke or presentation even With shock. So the type of patient we see today, it comes to the Cath lab is very different than 10 or 15 years ago and I think it's important to recognize when you're thinking about extrapolating the results of clinical trials to contemporary practice. Now, notwithstanding the findings of trials such as ischemia encourage and our guidelines that seem to tell us more or less clearly that how we should or in which patients we should be a performing coronary revascularization procedures. We still do see a fair amount of variability just like we see with the application of medical therapy. But this is these are interesting data from now Canada and in Canada. Perhaps some of the incentives that may influence practice in the United States, such as a fee for service model are not operative. So one might think that in Canada will see a little bit less variability. But in fact that's not the case. Um These are data looking at on the Y axis, the ratio of revascularization to medical therapy in the Canadian province of patients who have stable ischemic heart disease. What you can see is out here at certain centers, the odds of getting revascularization about 1.6 to 1.7 fold higher, whereas at some centres it's much much slower. And again, these are all stable patients who have coronary artery disease. And you can see a fair amount of variation in whether or not patients are getting or not receiving medical therapy versus coronary revascularization. And the authors delve into why we might be seeing that. And they modeled a whole host of variables, patient factors, which makes a lot of sense, hospitable variables, physician variables, but no matter what, they modeled this metric that articulates or quantifies the degree of variability stayed about the same. And so what they concluded is that the amount of variation we're seeing in, in implementation, in real world practice is not fully accounted for by patient physician level variables. They do find evidence that has been shown that other studies that some of our higher risk patients, those who might most clearly benefit from a more aggressive posture, important revascularization or at least likely to receive it interestingly, um, angiography, if you're an interventional cardiologist, certainly associated higher odds of getting revascularization. And so at the end, what these authors say, which I think makes a lot of sense is there are probably some degree of institutional preferences that may drive decisions over re basket some places versus another that we were just discussing a moment ago and perhaps some other implicit measures or unmeasured. Confounding is and biases. And what about the patient preference? Um ST paul alluded to this um as well, and this is something that is really being emphasized more and more at all different levels from NIH and onward, is that we really need to take into account patient preferences in decision making. This is an interesting study published 1019 where the investigators took a little over 200 patients and they developed a web based decision aid with the explicit purpose to educate patients about coronary disease, about quandary intervention with pcr versus cabbage. And what they did is they did a pre post analysis where they implemented this decision aid and look to see whether or not patient preferences and their knowledge about CED and revascularization changed importantly. About half of these patients actually presented with acute syndromes. They had a mean s excuse for 57. Again in the Ischemia trial, the average is accused for 81 indicating that these patients in this study, we're much more symptomatic. And what do they find? Well, here are the results and what they found is that PC I was certainly preferred much more frequently uh than medical therapy here at the top in the blue and it was also preferred much more calmly than it was for bypass surgery. This doesn't mean that tomorrow every single patient should be getting coronary revascularization, but it certainly does highlight the importance. I think it also highlights the challenges of taking in taking patient preferences into account these patients most of these quite symptomatic, a lot of them with acute coronary syndromes. And when these patients were enrolled in the study, they had already consented to undergo an invasive procedures that may have driven some of these decisions. But I think an important study highlighting that it's feasible to try to get patient preferences taken into account and we should Attempt to do so. So we have clinical guidelines, we have clinical trials with emphasis on patient decision making. How do we sort of try to put all this together? Well, just in case if you needed something else, you have the appropriateness criteria. Um these are were initially published in 2000 uh 11, um and most recently have now been updated for in 2017. And essentially with the authors of the EEC um state is that the eastern effort to assist clinicians and the rational use of Porto revascularization, common scenarios. And they provide a practical standard upon which to assess and understand variability. What does that actually mean? What that actually means is that the purpose of the EEC is to give us some more direct guidance in unique clinical scenarios that may not be addressed so clearly in clinical practice guidelines. So the way the EEC were operationalized is that um the developers of these criteria envision a whole handful of scenarios. These scenarios are bounded by the level of patient symptoms by medication. Is schema a noninvasive testing. Very important, particularly in light of the ischemia trial and burden of C. A. D. Um They assume anti additional therapies that maximally tolerated dose and then each scenario in the most recent articulation gets rated as appropriate may be appropriate or rarely appropriate. Now it's important to note that just because something is appropriate it doesn't mandate that revascularization is to be performed. And now obviously if something is rarely appropriate doesn't mean that we should prevent revascularization if it's the best thing for the patient. So here's an example of how these were implemented. So this is from the au see document for stable ischemic heart disease. You can see here you have a patient with two vessel disease, low risk findings on noninvasive testing and essentially no symptoms. You get a red are indicating that any type of real fast with PC. I. Or cabbage is not going to be considered appropriate. In contrast for those patients have intermediate high risk findings with two vessel disease but are quite symptomatic onto intentional drugs. Revascularization with either PC or bypass would be considered appropriate. So the general theme is that if you have minimal disease that's not optimally treated, revascularization is rarely appropriate as disease complexity increases, bypasses favored. Um There are some nuances to be aware of. With that highlight discords between guidelines that you see criteria. One is left Main. Most recent guidelines do give it to the recommendation for use of PC. I even with the syntax score between 23 to 32. But when it comes the appropriate use criteria, if you look at the very bottom you can see that if you have a bifurcation left main And the Syntex score with the threshold above 22, you get read ours anywhere for PC. I, even if you're quite quite symptomatic, so this is important to be aware of clinical practice should become familiar with these because what you don't want to do is do procedures and then you get report cards back indicating that you are not being appropriate with respect to your application of care. What do data show data show that over time it looks like there are more and more patients undergoing PC who are deemed appropriate as opposed to other categories. And variability is going down. And this either means that we actually are doing more appropriate procedures or perhaps we're getting uh more in tune with how to code and document. And that's what was suggested by this study. And on the left, you can see what these authors showed is that the proportion of patients who are presumably undergoing PCR for CCS three angina has gone quite dramatically since the introduction of the way you see on the right. You can see that the number of Pcs being performed for a CS, which includes unstable angina in the United States has certainly gone up, whereas in Canada it's remained more or less flat. So certainly there may be some component of documentation that's making the appropriate use criteria look a little bit better when we examine national data and then finally, an interesting study looking at what could be the implication of the ischemia trial. Now, what the authors did here is they said, well basically ischemia trial, we might assume that anyone who's asymptomatic would be classified as being rarely appropriate right now, that's not the case. But if the ischemia trial gets implemented with the A. You see that that is one interpretation and that would automatically shift the proportion of rarely appropriate cases from 3% to 22%. So in conclusion, I can say, is that medical therapy, lifestyle modifications certainly are the foundation for management or stable steaming heart disease. Although improving, achieving these goals remain a challenge. Um contemporary revascularization is characterized by more complex patients and procedures and overall decline abuse of any of these procedures. We see a lot of variability in the use of re Bhaskar medical therapy and clinical practice and the A. C. Provide us tools to guide decision making and the implications of the ischemia trial, particularly the reliance on the on the base of testing and the negative overall trial results on the east remain unknown. So I'll stop there and thanks for your time. All right thank you so much, Guzman. That was fantastic. I mean I think it kind of showed us your presentation, showed us um you know what the real world data actually shows compared to the stark contrast to the clinical trial data and you know how the A. U. C. Fits within our day to day practice. I just want to ask one quick question. Um You demonstrated how you know it's exceedingly hard to mimic the 80 adherence rate that we found in ischemia. What are some practical um tips to sort of get us closer to that level? Yeah, I mean, I think, you know, one challenge and modern day practices the issue of care coordination. Um you know, we just don't have enough time to see a lot of patients. Um so you know what one thing that I think helps a lot if you have a practice that can be set up that way um is having other advanced practice providers, um if it's nurses or nurse practitioners really being part of part of your team to help with that, the reality is I think as physicians we do a pretty poor job paying attention to some of some of these. And so thinking about the delivery of care, not as just a physician and a patient, but really as a as a team based approach I think is essentially mandatory, I think places that are able to do that have much better outcomes in adherence to some of these um um goals that have been outlined. Okay. All right, perfect. So in the interest of time, what we'll do is we'll do some casement yet. Well hopefully discuss and touch upon these topics. Um you know, we'll try to do as many as we possibly can in the time allotted to us. But let me uh start off the presentation here. So these are my disclosures. Let's just jump into the first case. So this is a 74 year old male. He is a retired executive has a history of hypertension, anemia and over the past year he has stressed being with heavy exertion. Specifically when he's Playing tennis, about 10 minutes into his Tennessee. That should be developed chest pain And then also with paying off on the back nine developed chest pain. It's obsessional radiates to the shoulder Um medications that he's currently on are valid on 25 atorvastatin 20. Um and he was referred to a general cardiologist due to his ongoing pain. The PCP started on the toe ball 25 in hopes of Obviating his symptoms. Um and then also starting on an aspirin and was ordered an echo and a nuclear stress test. So he goes, uh he gets his echo, which demonstrates that is normal by ventricular function with some mild M. R. Um He continues to have angina uh but only with high levels of exertion. So we just want to pause for a few seconds here on s Street Ball with a patient with this background, fairly active, um, develops pain with heavy exertion. Would you do anything aside from up tight trading medical therapy at this time? Yeah. You know, so this will be a conversation with the patient. I mean, it's critically important to give him options and say, look, we have two options. One is to say, let's keep updated in your medications and if you feel better and you're completely satisfied with it, that's the way to go. But you also have an option of saying, let's let's uh, you know, do an angiogram and see um where you are. I mean, that being said, if you do up the the option of medical therapy alone, you'd rather make sure that you're the patient does not have left main disease. So, I would say some form of testing to make sure the patient does not have left main disease is important. All right. So, uh, so exactly what you stayed into, his metropol was doubled to 50. Um and he also underwent a noninvasive test specifically to assess for something that could be very high risk. And so he was able to go on for some period of time. So he went on for about 11 minutes and 47 seconds um for his exercise spec maybe, but had to stop doing chest pressure and the study demonstrated moderate to severe in for your s senior, um He still continues to have pain with uh with his exercises. So with this information, would you do anything at this point aside from increasing his medical regiment or would you take on the task at this time? Yes, I'll tell you so. I think, you know, I would have probably done a ct a to start off with. So I've been doing that more and more in my practice and um just to get just to get an answer and particularly with what ST paul and the schema investigators showed. But now with this information, um you know, my bias, certainly someone who is very active. Um you know, I want to make sure um uh there's nothing that I'm going to be terribly concerned about. So with this patient who still having still having symptoms and they're very active, I'm going to want to take in the catholic with these findings. Yeah. I mean that's precisely what I thought. Um and that's what I thought we wanted to do. But the issue is that this patient has a partner who unfortunately had a recurrent S. R. Um and now has intractable angina. And so with that backdrop, the patient felt that he absolutely wanted to avoid any sort of invasive therapy unless absolutely needed. So uh what we decided to do was to say, hey, if you have left made then obviously we need to do something more substantiative if you have multi vessel disease. Um That was fairly significant. That that would be a conversation towards cats. So um he agreed on a coronary sita in the coronary ct a demonstrated cad rats for a, so he had uh you know greater than 70% stenosis of his mid R. C. A. And 50 to 69% stenosis of his pistol left circle. So with that being said, what we decided to do was to continue to optimize his medical therapy. His medical therapy, we put them on top of all 100 mg. However, he became more braddock arctic. He felt a little bit more sluggish, a little bit more tired. So instead we started him on indoor type, traded that up and then um he became minimally symptomatic altogether. He was able to complete the people of the gulf as well as his sessions with this kind of pro, so with that being said, you know this was a case where we use medical therapy, didn't have to do anything invasive and the patient got a optimal outcome is still fairly active, still fairly robust without any sort of issues. Now let's go to another case. So this is the case of a 69 year old with hypertension, Hyperloop Adina and is a type one diabetic in this patient had six months of angina with just moderate exhibition medications include not only insulin but my since april and a lot of pain, atorvastatin and aspirin. He started on material XL 12.5. He started on a lower dose instead of the traditional 25 just due to some baseline braided cardio. He tolerated it well. Um he got an echo that showed an LVEF of 64 with a mildly dilated aortic group. Um And like Guzman stated he actually went for a coronary ct A as his first noninvasive test and it demonstrated that he had severe stenosis of the left anterior descending left sir complex and the right coronary artist, but notably no left main. So shrimp all in the context of the ischemia trial, what would you do here? Yeah, I think this is a great example. Again, he has preserved the F. And yes, severe triple vessel disease. And again, this is another patient where I would discuss the pros and cons of both approaches. I mean, the critical important piece to me in any kind of this discussion is you're not, I mean, if you choose medical therapy, the key thing to understand is you're not wrong. I mean, and it's not like you are stuck with that decision forever. I mean, you know, I think that's critically important to emphasize. Look, I mean, you can try this if you're chest pain doesn't get better or if you are dissatisfied with it, we can really consider revascularization at that point. Um So I I think it's more of informing patients of options and letting the patient choose. Yeah. So with that being said, I mean I think that the fact that he was a diabetic, the fact that it showed multi vessel disease. We were convinced and he was convinced that probably invasive route may be superior for him. And so here you see his ap coddle, it demonstrates he has prostate disease. He also has on disease. He has an led with a middle of the stenosis uh and large diagonal that also a fanatic. These are some additional abdominal views from highlighting the same disease. Um And then the right coronary shows that he has fairly diffused long calcifications ease in the mid right. And then also, you know this is potentially at the cost of the P. D. A. So on the basis of this. What would you do as a form of treatment response? Would you go with continued guideline director medical therapy? Would you proceed with cabbage or would you perform multi vessel Pc. I, knowing that you could do a complete reverse. Yeah it's a great question. I mean I think the issue, at least for me, my practice um you know when you think about a patient like that and PC I what we have to remember, not all diabetics are the same. Um and you know there's some diabetics are going to present with a couple of focal lesions. Pc. I is great. The challenge here. What I try to think about is how many millimeters extent, how much stent are are we going to have to do? And what level of complexity? Because we know there's a lot of data showing more complexity. Particular diabetic patient, greater risk for both instant restenosis or sent thrombosis. So um this kind of patient, I don't think it's going to be the best candidate for multi vessel Pc. I. Unless he's deemed prohibitive risk for uh for bypass surgery. So somebody like this with including led disease, bifurcation disease, that kind of tortuous circuit that R. C. A. I. Would refer for bypass surgery. Yeah. So his syntax score was calculated to be 26. So that puts him in the intermediate church style is sts problem was calculated to be significantly low at 0.4%. And so on the basis of that, just like you we decided to reform for cabbage where he got complete re vest. Um It was a lima to the L. E. D. S. P. G. To the diet. Spg to the survey. S. V. G. To the O. On an spg to a R. C. A. With a jump to the R. P. D. A. Um I think for the interest of time I think we'll stop here. Um There are obviously other case vignettes and it's sort of odd that for a stable ischemic heart disease talk that was sponsored by a vascular interventions company. We didn't actually show any vascular inventions. We actually showed medical therapy um and we actually showed bypass surgery but I think it sort of speaks to the management of stable ischemic heart disease. I think that it's evolved over time. We've obviously become much more nuanced than the way we treat our patients. Were much more thoughtful incorporating clinical trial data but also taking into account real world practicalities as well as patient preferences. And so I hope that based on the seminar tonight that you guys watching had a were able to take away a lot from this session with that being said uh you know, I just want to conclude with a few final words from our panelists treat Ball Guzman, anything else to add? I think we've summarized it very nicely. I think the critically important thing to remember is one size does not fit all and patient centred decision making is critically important. Yeah, I just want to thank for the chance to discuss this with you. It seems like it should be pretty straightforward based on the results of all the clinical trials, but you can see it really is a lot of gray. Um and and so I think all these points were um you know very well taken and need to be implemented in our day to day practice. So again, I want to thank you both tree pollen Guzman for joining us tonight. I also want to thank bio chronic for their continued support before you all sign off. I do want to put in a small plug for the next bio emerged webinar um at the right of the video player is a link to register for maize biomarkers webinar, which will focus on cath lab pharmacology and spent design. Also, our prior webinars are now on the website as well. So thank you again. Um, and we appreciate you joining us tonight. Take care. Thank you. Thank you. Mhm.