So, my name is Dr. Michael Block, I'm a hypertension and vascular medicine specialist here in the great state of Nevada. Here you see my disclosures that are relevant to tonight's presentation, and really what I want to do over the next 10 minutes is sort of just walk you through the story of where we're going in terms of emerging treatment paradigm, I think, for renal denervation, assuming the data continues to look the way it has in the past. It's actually a pretty simple story, if you sort of follow the data that Eric gave, the clinical trial designs that Ray presented, and then the data that Ray presented, I think we're really walking ourselves towards being able to identify reasonable patients to consider for this therapy, and a reasonable way to deliver this therapy in our communities. So as Eric, I think, so nicely mentioned, we really are focused as providers on that 35% of treated patients who are not controlled, clearly, one of the things that jumps out about those patients is they are not adherent to their medications. And as Eric so nicely pointed out, adherence is not easy to measure, and it's not necessarily black and white, it is dynamic, but it's clearly a problem in the treated but not controlled hypertensive patient. And I think it's worth at least thinking about how renal denervation as a one-time procedure with a presumably durable effect that reduces the dependence on medical adherence may affect those control rates, also has the benefit of reducing the potential for side effects from antihypertensive medications, and of course, reducing pill burden as well. And if you, once again, I think now I'm the third person to show data from the meta-analysis from the blood pressure trials collaborative group. But once again, if you look at what the data shows that Ray shared with you about that 8 to 10 millimeter reduction in clinic blood pressure, that is a reduction that clearly, at least in our patients with higher absolute cardiovascular risk is going to give us reasonable reductions in cardiovascular events down the road, if in fact, renal denervation works in the same way that medicines do in reducing cardiovascular risk. So really when you think about the next steps, when we think about that patient who's treated and not controlled from the clinician point of view, the real question to me is when a patient like that walks into my office, a patient who's treated but not controlled, I can't just do nothing. I need to increase that patient's therapy in one way or the other. So the real question is, what is the relative risks and benefits of adding another antihypertensive medication versus potentially offering that patient renal denervation? And I think when we look at that question, it's important to recognize that there's a wide variety of patients that are going to be coming into our office and that there's a number of different domains we might want to look at when we address that question. So first of all, in terms of those different medications, different patients that are going to walk into our office, as you see in the middle of this slide, they're really going to be on a spectrum of background medication. We're going to have patients who may have been prescribed medicine in the past, but they're not taking any due to perceived or real side effects. We may have patients who are uncontrolled despite one or two medications, and we may have patients who have apparent treatment-resistant hypertension who've at least been prescribed three or more medications. And I just want to point out that even in these early days of renal denervation 2.0, we actually have data with all of these different patient groups. Across that, we have data with spiral-off medicine and with Radiance Solo on patients on zero medications. At the other end of the spectrum, we have data from Radiance Trio that looks at patients who are on three or more medication. And we're increasing data in that middle group of patients who are uncontrolled despite one or two medicines. We have the spiral on-med pilot study. We also have some data from Radiance Solo where patients were put back on medication after that initial two-month endpoint. And looking at six-month data, even with the background of that medication, renal denervation appeared to offer a benefit. So we really have benefit in terms of efficacy across that spectrum, but it's important not just to look at efficacy when we examine these patients. We want to think about tolerability, which may favor renal denervation over medications. We need to look at safety. And at least in the data we have to date, renal denervation does appear to be safe, as does medical therapy. We have to think about adherence. And as we've already alluded to, I think that renal denervation offers an adherence-independent therapy that may offer advantage in some of our patients who don't like taking the medications that we prescribe. And in terms of durability, I think it's something that we really need to think about. Ray talked about the 24-hour durability of renal denervation, but I think we need to be really sure that this strategy does control blood pressure for months to years into the future. And so far, I think all of the data that we have from the registry does suggest that, in fact, it is a durable effect. Cost is something that we're going to have to think about moving forward. I think we need to think about cost in a little bit of a different way. Obviously, the upfront costs of renal denervation, we don't know what it'll be here in the U.S., but the upfront cost of renal denervation will certainly be more than adding a medication. But remember, there are ongoing costs to the treatment of hypertension. Patients may be paying only $10 a month for their medicine, but they're paying that month after month after month. And don't forget that if we're not controlling blood pressure because patients aren't adherent with their medicine or are not controlled, they may have ER visits, they may end up with cardiovascular events, all of which can be quite expensive. And then patient preference, I think, is really going to be a key. I think there are going to be some patients who really don't mind adding another medication, and there are going to be some patients who really would like to potentially explore renal denervation. And that's going to be a real important part of the pathway moving forward, is what does that patient think? Are they the type of person who wants to consider renal denervation, or are they the type of person who are going to be adding more medication? So on the strength of the data that we have available, we have a number of groups around the world who are now commenting on the fact that renal denervation does seem to be approaching the prime time for utilization in our treated but not controlled patients. The European Society of Hypertension just put out this consensus document earlier this year, and I will just quote from it, on the basis of the consistent results of several sham-controlled clinical trials, renal denervation represents an evidence-based option to treat hypertension in addition to lifestyle changes and blood pressure lowering drugs. But I think one of the important things that they point out is that we need to be choosing the right patient, and we need to be doing it as a part of an overall structured approach to treating their blood pressure. It's not that we denervate them and forget about them, it's that we denervate them and continue them on medications and lifestyle changes, and if anything, we may need to accelerate those medicines as well as offering a patient denervation. So in just the next couple of moments, I just want to start to think a little bit about who might be the ideal candidate for consideration of renal denervation, when and if it becomes available in this country. And what you see on this slide is not just my opinion, but the opinion that was published of this expert consensus panel that Sky and the National Kidney Foundation recently put together. You see the references there on the slide if you want to look it up. I think we're starting to think about the ideal candidate as being one who has persistent uncontrolled hypertension despite prescription of guideline-based therapies that is treated but not controlled, not necessarily resistant, but treated but not controlled over a number of months and a number of visits. I think importantly, we want to confirm poor control, not just in the clinic, but by out-of-office blood pressure monitoring, either home devices or 24-hour ambulatory blood pressure monitoring. We want to be sure that we're excluding secondary cause, particularly renal artery stenosis in these patients. And I think that we want to be generally affording this therapy to patients who are at higher cardiovascular risk. One of the things that has really come out of all of the observational data is that all patients get the same relative risk reduction from 5 to 10 millimeters of blood pressure monitoring. But clearly, those who are at higher cardiovascular risk, including those who have had prior established cardiovascular disease, are going to get the greatest absolute benefit from that reduction in blood pressure. And then patient preference and shared decision-making, of course, are going to be a very important part of the process. We're going to want to have endorsement by more than one provider with appropriate specialty backgrounds, something I'm going to be talking about in just a moment. And I think we want to make sure that there's an experienced interventional specialist who's available in that community to perform the procedure. So that's really what we're thinking about in terms of the ideal candidate. But I think we also need to start thinking about what is the ideal center? What is the ideal structured program to be offering renal denervation? Remember, the idea is not just to denervate and forget about these patients. The idea is to, one way or another, get their blood pressure under control. So once again, this expert consensus panel really thought a lot about this question. And what you see on this slide, I think, is a nice schema of what one of these interventional hypertension centers of excellence might look like. We want, of course, an endovascular, experienced endovascular interventionalist, but working in conjunction with a clinical hypertension specialist. In a couple of centers, those might be the same place, the same person, but I think in most of our centers, those are going to be two separate individuals and maybe groups of individuals who are working together. And once again, we want this to be part of a structured program in the community where those individuals in that center is willing to do the hard work of investing in the institution and the community to raise awareness about the program, to do outreach to providers, outreach to patients, and importantly, to engage payers to make sure that it is being reimbursed in appropriate fashion for our patients, and then who are willing to take part in outcomes assessments and registries for the long run. So this is really sort of where I think we're heading in terms of the appropriate patient pathway and the appropriate institutional pathway for renal denervation in the United States. And with that, I will turn things back over to Dr. Ferdinand, and I look forward to hearing your questions later in the program.

renal denervation

hypertension treatment

medication adherence

cardiovascular events

shared decision-making