Activity Transcript

Roland Schmieder, MD: Hello, I'm Roland Schmieder, professor of internal medicine, nephrology, and hypertension at the University Hospital in Erlangen, Germany. Welcome to this program, titled, "Where Does Renal Denervation Fit in the Landscape of Blood Pressure Control?" Joining me today is Sofie Brouwers, who is a cardiologist and hypertension specialist at the OLV Clinic, Aalst, and professor at the Vrije Universiteit Brussel.

Sofie, welcome.

Sofie Brouwers, MD, PhD: Thank you.

Dr Schmieder: Hypertension is a global epidemic, and I think it's the most important epidemic while it affects 30% of the world population. This is a treatable and modifiable risk factor, and the importance of hypertension relies on the fact that is attributable to premature cardiovascular death. It is the major risk factor for heart failure and stroke, also for myocardial infarction, peripheral artery disease, and chronic renal failure. Now hypertension cannot be cured, but it can be treated effectively. If you achieve blood pressure control, we know that then the cardiovascular risk, the risk of developing renal failure is substantially reduced. Though this is our therapeutic goal to reach target blood pressure below 140 over 90, at least, at best, below 130 over 80 mmHg. Hypertension is the most important and modifiable risk factor, and I think we will learn throughout this course how we can treat hypertension and what are the options we have today in 2023.

Dr Brouwers: Thank you, Roland, for the nice introduction. Can you then elaborate a little bit more on how do we have to approach the blood pressure control?

Dr Schmieder: We have now I think 3 pillars of antihypertensive therapy. First, the lifestyle changes. Most important is a diet low in sodium, low in alcohol, rich in vegetables, rich in fruits. We have to increase our exercise, and we have to also increase our intention to reduce body mass index -- obesity. That's very hard, but it can be achieved in several cases to at least even 2 kg to 5 kg less, they count. The second pillar is a combination drug therapy, and we have now several preferred drug classes, such as renin-angiotensin blockers, the ACE (angiotensin-converting enzyme) inhibitors, the angiotensin receptor blockers, calcium channel blockers, and the thiazide and thiazide-like diuretics. Then according to the most recently presented guidelines by the European Society of Hypertension '23, just a couple of weeks ago, we also have now the beta blockers as one of the major drug classes, particular if we have special indications to use beta blockers, those coming from the cardiovascular field.

I think it's very important to stress also we have a novel intervention now, namely the endovascular renal denervation, which enters now the market because of several good data. We have SGLT2 inhibitors, and nonsteroidal mineralocorticoid receptor antagonists should not be forgotten. They are usually used for organ protection. We also have learned that they have some substantial reduction in blood pressure, which in some cases is forgotten to mention. Sofie, now coming to the point, what about the blood pressure control? How effective is it? How poorly controlled is it?

Dr Brouwers: There is indeed a problem. You just pointed out all the different possibilities we have to control blood pressure. So, it is possible, but it is definitely not achieved. There's, up until now, a very poorly controlled blood pressure rate worldwide, and it's due to a couple factors. First of all, there's obviously adherence to lifestyle that is very poor. People continue eating unhealthy diets, they are overweight and continue to have a sedentary lifestyle and have very stressful lives. So that is a problem. Then we have a lot of drugs in combination therapy possible, but there's sometimes intolerance, but the biggest problem there is definitely adherence. The adherence to medication is very poor, especially also in hypertensive patients and the persistence on the long term.

The other problem we face is that there are problems with the healthcare system and with the doctors. On the level of the doctors, the problem is the therapeutic inertia. Doctors will often fail, actually, to start or to increase the dose of the medication or to start extra medication to improve blood pressure control. As such, blood pressure remains very poorly controlled in the world today.

You just said that we have the renal denervation now as a fourth arm of the treatment. Can you explain us a little bit more where this fits into the clinical management of patients with hypertension in these days?

Dr Schmieder: This is very a timely question I think, because in the 2023 guidelines, we have really a change of the recommendation with respect to renal denervation. First of all, in 2018, we had a red color meaning no recommendation. Now we have a class II recommendation; it has been upgraded because of the, I would say, overall evidence for sham-controlled randomized trials that show that renal denervation exerts substantial blood pressure reduction on the average between 10 and 20 mmHg. It's not a class I because the grading system at the European Society of Hypertension has changed, and class I is only if we have data on morbidity/mortality. We do not have that. On the other hand, very clearly lifestyle changes, which they're mentioned, pharmacotherapy, these are the cornerstones. But once we cannot achieve these goals, we have options with renal denervation, an option that is now recommended by the guidelines.

In patients with CKD stage 1 to 3, once we have 3 of the 4 major drug classes, we have the question, should we add spironolactone? Should we add an alpha blocker? Should we have a beta blocker or a centrally acting agent? Most important, it is also now mentioned in the guidelines, renal denervation can be considered as a treatment option in patients with an estimated glomerular filtration rate (eGFR) above 40 in uncontrolled blood pressure. It is, I think, timely, and it is important that we to choose now this new option into clinical practice.

Sofie, I mentioned these clinical trials and maybe you can elaborate a little bit on what are the intervention options we have, what are the data we have about the efficacy of renal denervation?

Dr Brouwers: Yes. In the recent years, there's a lot of publications that came out on renal denervation. In the recent clinical consensus statement of the European Society of Cardiology (ESC), we actually evaluated the scientific data and the quality of it. And so we found that there's quite some multicenter, randomized, sham-controlled and blinded trials that used ambulatory blood pressure as the primary efficacy outcome for renal denervation. There they showed actually that both for the radiofrequency and the ultrasound renal denervation in a large range of patients, the results were overall very positive. When I say a range of patients, I mean patients with mild to moderate hypertension but also patients with severe to resistant hypertension; so really, in the whole scale of hypertensive patients. For efficacy, we have now very reassuring data. Then for the question of durability, we have data not only from randomized-controlled trials but also from registries. Up until now, we see a sustained blood pressure-lowering effect of renal denervation at least for up to 3 years now with everything that is published. Concerning the clinical evidence, we have way more to build on in these days.

If we then ask the question what do we know about long term? I just said we have this sustained blood pressure, but do you think this is a good option for blood pressure control on the long term?

Dr Schmieder: I think this is one of the most important questions, actually also asked by patients who we have treated so far with renal denervation: How long does it last? You mentioned these data about 3 years, and they are really, I can confirm, very solid data from clinical trials. For example, we have 3 years follow-up data. We have from SYMPLICITY Registry, a large-scale registry with more than 3000 patients, data up to 3 years. We are having a very solid base that it lasts at least to the same extent by which we observed after 3 to 6 months.

Most important, I'm aware of also clinical series in Germany, one from Hamburg in Saarland, and also from Australia. We have followed up patients now for 9 years.

It's very intriguing to me that they all have excellent blood pressure control, far better than they have observed after 1 to 3 years. Though there is a continuous and long-lasting effect. I think from a clinical perspective, despite some confusing experimental data, I do not want to discuss that because they are conflicting. From a clinical perspective, we can really say to our patients at the moment I'm confident that it lasts up to 9 years. This brings up the question of course now about this strong statement for the efficacy and the excellent blood pressure reduction. We come to our most important point about safety. We have not talked about that. I think there's a need for that. Sofie, can you just give us the data on that?

Dr Brouwers: Absolutely. Talking about patients and interventional procedure, obviously the first question is safety. If we start with acute safety concerns, it's obviously related to the procedure, and there we see, actually, that there is no evidence of a significant procedure-related safety concern beyond the risks associated with femoral arterial access or with radiation.

If we then look at to the middle- and the long-term concerns related to renal derivation, questions have been arising about renal artery stenosis and acute or chronic kidney injury. We can say that with the long-term follow-up data, as said, up to 3 years there's no significant increase in renal artery stenosis or in worsening of kidney function beyond the expected rates that are known in hypertensive patients. Here it's important to say, patients with an eGFR below 40 mL/min are excluded from the trials and have not been denervated. So, for safety, I think we can definitely conclude that all these data are looking perfectly good. Then we actually get to the question, how can we now implement renal denervation in our clinical practice? What do you think, Roland?

Dr Schmieder: We just released guidelines by the European Society of Hypertension give us some good guidance on that. They suggest that we need certified hypertension centers. Now this would be a new step for the device-based medicine. Usually for most of these interventions, which have been done today, there are no certified hypertension centers on a European or worldwide basis. I think it's a good way that we do implement renal denervation in clinical practice by a structured pathway. The reason for that is we have to consider that this is an intervention done usually by interventional cardiologist or interventional radiologist and also by a hypertensionologist, even maybe cardiologist, nephrologist, even maybe primary care who is experienced in hypertension. They refer the patient to where? They need to refer to some centers and make a common decision to say, well, this patient is eligible for renal denervation according to the guidance we have.

This structured way in certified centers is also a very clear signal to the payers. We do this in a certified way. By doing this in a certified way, the patient's voice is also more here than before. The patient's perspective is important because we need to ask the patient, well we have 2 options, one of the drugs, which are not so well proven, spironolactone, alpha blockers, no good data on long term, as well, even a lot of side effects. Renal denervation, we should discuss these pro and cons in a shared decision-making process in such a certified center really is a good basis to implement renal denervation in clinical practice. I think we are on the right track there.

Dear colleagues, let me summarize some of the talks and points that have been made, in 3 simple take-home messages. First, renal denervation is in the transition phase from science to clinical practice, entering now routine clinical practice in uncontrolled, in particular, in uncontrolled resistant hypertensive patients and those who cannot tolerate drugs, there it represents an option. Second, no doubt about it, renal denervation lowers blood pressure effectively and also reduces sympathetic activity in the whole body, which open the window that we’ll hear more about renal denervation in terms of can it be specific cardioprotective, for example, atrial fibrillation? Can it be specifically nephroprotective to stop progression of renal disease, or this will be new fields of research? For now, we have a very solid base, and we have 5 randomized sham-controlled trials, the highest level of evidence we can ever achieve that renal denervation is effective, and thereby we have a solid basis to implement this in clinical practice.

Safety, Sofie has mentioned and summarized very nicely, it is safe and there's no particular -- the cautions were at the beginning, does it cause renal stenosis? Does it cause renal progression or renal failure? Just this is not the case. No signal at all. This is really one very simple thing. You can be relaxed about safety.

Finally, I think this new option also introduces the most important point in hypertension care: to hear the patient's perspective. Why is he intolerant? That may be just simply he has not understood any kind of the disease. Most important, what are the side effects he cannot tolerate or is afraid of toxicity? If this is the case, then we have also now discussed with the patient that renal denervation represents an intravascular procedure that can be performed without any safety reasons. One point, once the renal denervation is done, you do not need to take care about the adherence issue. It is done. This is a very good point, which should be more stressed in our conversation with the patients, particularly those who said, "Well, another drug to control our blood pressure. Is there an option?" Well, renal denervation is a 1-time intervention, and then it's done. Here, and once again, shared decision-making process is important in the implementation of renal denervation, in clinical practice.

Thank you, colleagues. Thank you to the audience to listen to this seminar. Sofie, thank you for this great discussion, and thank you to the viewers for participating in this activity. Please continue on to answer the questions that follow and complete the evaluation.

This transcript has not been copyedited.