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PARIS – Endovascular device–delivered renal denervation has been dramatically resuscitated as a promisingly safe and effective nonpharmacologic treatment for hypertension on the basis of two rigorous positive, prospective, sham-controlled, randomized trials presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“These two trials are proof of concept. They were not intended to show superiority of denervation over drug therapy. They provide the proof of principle that when we interfere with the renal sympathetic nervous system we are able to lower blood pressure,” according to Felix Mahfoud, MD, an interventional cardiologist at Saarland University Hospital in Homburg, Germany, who was a coinvestigator in both trials.
As a longtime investigator in the field, he was selected by the EuroPCR 2018 organizers to present an official statement to attendees in conjunction with presentation of the two late-breaking clinical trials. The essence of the official commentary was that, despite what physicians have heard based on earlier major setbacks, renal denervation (RDN) therapy for hypertension is alive and well; it’s an active area of investigation; and it holds promise for addressing the vast unmet need for better control of hypertension.
“It’s an interesting field. EuroPCR is committed to further support of the field. Stay tuned; there’s more to come. It’s been a bumpy road up until now, but I think we’re back on track with renal denervation,” Dr. Mahfoud said.
A few years ago RDN was widely dismissed as a failed treatment strategy on the basis of the negative results of the phase 3 SYMPLICITY HTN-3 trial conducted in patients with multidrug-resistant hypertension (N Engl J Med. 2014 Apr 10;370[15]:1393-401). Since then, two European consensus conferences on device-based hypertension therapies were held in 2015 and 2017. Those meetings analyzed key mistakes in earlier research and identified three key confounders that need to be standardized in order for high-quality research to move forward: The use of antihypertensive medications, or lack thereof, must be fixed and consistent; patients with severe treatment-resistant hypertension for whom basically nothing works are not the population to study initially; and key trial design and procedural details for the various endovascular therapies in development must be agreed upon.
The two sham-controlled trials presented at EuroPCR 2018 utilized different ablative energy sources: The RADIANCE-HTN SOLO study employed an ultrasound catheter, while the SPYRAL HTN-ON MED trial used a radiofrequency device. Both devices remain investigational. Each aims to ablate both the afferent and efferent renal sympathetic nerves located in the adventitia that run to and from the brain.
RADIANCE-HTN SOLO
Laura Mauri, MD, professor of medicine at Harvard Medical School, Boston, reported on 146 patients with mild to moderate hypertension at 39 U.S. and European centers, all of whom were deemed anatomically suitable for device therapy on the basis of the results of renal angiography. After a 4-week antihypertensive medication washout period, by which point their average blood pressure had climbed to 150/93 mm Hg, they were randomized in single-blind fashion to endovascular ultrasound RDN using ReCor Medical’s Paradise system or to renal angiography as a sham procedure.
The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months’ follow-up post procedure in an intent-to-treat analysis. The RDN group had an 8.5–mm Hg reduction from baseline, compared with a 2.2–mm Hg reduction in sham-treated controls.
In a per protocol analysis excluding the five patients in the RDN group and 13 controls who required antihypertensive medication during the 2-month follow-up period, the average reduction in daytime ambulatory SBP was 8.5 mm Hg in the RDN group and 0.1 mm Hg in controls.
Similar statistically significant and clinically important placebo-controlled reductions in blood pressure were seen in all other endpoints, including 24-hour ambulatory, office, and home blood pressure.
“To put this in context, the magnitude of effect observed both on ambulatory blood pressure as well as office blood pressure is comparable with differences in blood pressure associated with reduction in cardiovascular events in population-based studies and meta-analyses of antihypertensive medication randomized trials,” Dr. Mauri observed.
At 2 months, 20% of the RDN group had a blood pressure below 135/85 mm Hg in the absence of antihypertensive medication, compared with 3% of controls.
No major adverse events such as renal failure, major vascular complications, embolism with end organ damage, or hypertensive crisis occurred during 2 months of follow-up. Follow-up will continue out to 3 years to evaluate the durability of therapeutic benefit.
The Paradise ultrasound system achieves circumferential ablation at a controllable depth of 1-6 mm in order to interrupt renal nerve traffic. Two or three ablations, each lasting 7 seconds, are delivered to each of the main renal arteries. The arterial wall is protected by water circulating through the balloon. The results were published simultaneously with Dr. Mauri’s presentation (Lancet 2018 May 23; doi: 10.1016/S0140-6736[18]31082-1).
SPYRAL HTN-ON MED
David E. Kandzari, MD, reported on the first 80 patients to complete 6 months of prospective follow-up in this ongoing international, single-blind, randomized trial of more than 400 patients with inadequately controlled hypertension on one to three commonly prescribed antihypertensive medications. Participants are being randomized to RDN via circumferential radiofrequency ablation using Medtronic’s Symplicity Spyral catheter or a sham control procedure. Although in this trial patients remain on their antihypertensive medications, an earlier randomized trial established proof of principle for efficacy in the absence of antihypertensive drugs.
In the real RDN group, 24-hour ambulatory blood pressure fell from baseline to 6 months of follow-up to a statistically significant and clinically meaningful degree: by 9.0 mm Hg systolic, compared with 1.6 mm Hg in controls, and by 6.0 mm Hg diastolic versus 1.9 mm Hg with the sham procedure. Similarly, office blood pressure fell by 9.4/5.2 mm Hg with RDN, compared with 2.6/1.7 mm Hg in controls.
Notably, 24-hour ambulatory systolic blood pressure was significantly lower in the RDN group around the clock.
“This may have important considerations with regard to pharmacotherapies with pharmacokinetic peaks and troughs in the early morning hours and late evening, or perhaps for groups with hypertension who are at especially high risk for cardiovascular events, such as those with nocturnal or early morning hypertension,” observed Dr. Kandzari, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute in Atlanta.
“This raises the concept of an ‘always on’ effect for renal denervation therapy that may be in distinction to pharmacotherapy and independent of adherence issues,” he added.
And speaking of adherence, a key feature of SPYRAL HTN-ON MED was that the trial incorporated periodic drug adherence monitoring using both urine and blood testing. The results, Dr. Kandzari said, were eye opening: At any given time, roughly 40% of patients in both study arms were nonadherent to their antihypertensive medications. Moreover, nonadherence was dynamic: It was not predictable for any single patient at any time point.
This 40% nonadherence rate was surprisingly high given that participants in SPYRAL HTN-ON MED were volunteers eager to participate in a non–drug treatment study and were informed up front that they would be undergoing adherence testing.
As in RADIANCE-HTN SOLO, no safety issues arose during follow-up in SPYRAL HTN-ON MED. The results were published simultaneously with Dr. Kandzari’s presentation (Lancet 2018 May 23; doi: 10.1016/S0140-6736[18]30951-6).
One difference between the two technologies is that, unlike the ReCor Paradise ultrasound catheter, which ablates in the main renal arteries, the Medtronic radiofrequency device is placed in the side branches.
Asked whether he sees RDN, provided it is established as safe and effective, being used primarily in hypertensive patients who are on or off medication, Dr. Kandzari replied that his personal view is it will have a role in both. Some patients would prefer not to take drugs. For others with uncontrolled hypertension despite multidrug therapy, RDN could serve as adjunctive therapy that reduces their need for medication.
Unanswered questions
Additional studies of both technologies are ongoing, and pivotal large phase 3 trials are being planned, with results expected in the next year or 2. Asked if regulatory agencies are going to require large, long-term trials with hard cardiovascular endpoints as a condition for approval, Dr. Mauri said a strong case can be made for bypassing this step.
“Blood pressure is remarkable,” she replied. “It’s one of the strongest surrogate endpoints that we have in the medical literature. It’s supported by multiple randomized trials of antihypertensive therapies, which have shown that reductions in blood pressure are associated with reductions in mortality from cardiovascular events. That’s really the gold standard for a surrogate endpoint. So I think it’s convincing. That being said, I would be very interested to also see hard endpoints in the long term, but that will take time.”
And time is a luxury in light of the escalating global hypertension pandemic. Dr. Mahfoud noted that it’s estimated that in 2015, 950 million people around the world had a systolic blood pressure in excess of 140 mm Hg. By 2025, that figure is expected to climb to 2.5 billion people. The Centers for Disease Control and Prevention estimates that more than 360,000 deaths per year in the United States have hypertension as the primary or a contributing cause. Blood pressure control rates remain unacceptably low, in the 50% range. Nonadherence is high. So there is a pressing unmet need for new forms of treatment.
Dr. Mahfoud cited three major remaining research priorities for RDN therapy. There is a need for some form of intraprocedural feedback to inform the interventionalist while still in the catheterization lab that the denervation is successfully completed. A reliable predictor of response is desirable so that likely nonresponders to RDN aren’t needlessly exposed to the procedure. And of course, the sustainability of benefit for RDN requires longer-term study.
Dr. Kandzari reported receiving institutional research support and consulting fees from Medtronic and several other medical device companies. Dr. Mauri reported receiving institutional research support from ReCor and other device companies and serving as a consultant to ReCor and Medtronic; in addition, she has accepted a position as a vice president at Medtronic to begin in September.
PARIS – Endovascular device–delivered renal denervation has been dramatically resuscitated as a promisingly safe and effective nonpharmacologic treatment for hypertension on the basis of two rigorous positive, prospective, sham-controlled, randomized trials presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“These two trials are proof of concept. They were not intended to show superiority of denervation over drug therapy. They provide the proof of principle that when we interfere with the renal sympathetic nervous system we are able to lower blood pressure,” according to Felix Mahfoud, MD, an interventional cardiologist at Saarland University Hospital in Homburg, Germany, who was a coinvestigator in both trials.
As a longtime investigator in the field, he was selected by the EuroPCR 2018 organizers to present an official statement to attendees in conjunction with presentation of the two late-breaking clinical trials. The essence of the official commentary was that, despite what physicians have heard based on earlier major setbacks, renal denervation (RDN) therapy for hypertension is alive and well; it’s an active area of investigation; and it holds promise for addressing the vast unmet need for better control of hypertension.
“It’s an interesting field. EuroPCR is committed to further support of the field. Stay tuned; there’s more to come. It’s been a bumpy road up until now, but I think we’re back on track with renal denervation,” Dr. Mahfoud said.
A few years ago RDN was widely dismissed as a failed treatment strategy on the basis of the negative results of the phase 3 SYMPLICITY HTN-3 trial conducted in patients with multidrug-resistant hypertension (N Engl J Med. 2014 Apr 10;370[15]:1393-401). Since then, two European consensus conferences on device-based hypertension therapies were held in 2015 and 2017. Those meetings analyzed key mistakes in earlier research and identified three key confounders that need to be standardized in order for high-quality research to move forward: The use of antihypertensive medications, or lack thereof, must be fixed and consistent; patients with severe treatment-resistant hypertension for whom basically nothing works are not the population to study initially; and key trial design and procedural details for the various endovascular therapies in development must be agreed upon.
The two sham-controlled trials presented at EuroPCR 2018 utilized different ablative energy sources: The RADIANCE-HTN SOLO study employed an ultrasound catheter, while the SPYRAL HTN-ON MED trial used a radiofrequency device. Both devices remain investigational. Each aims to ablate both the afferent and efferent renal sympathetic nerves located in the adventitia that run to and from the brain.
RADIANCE-HTN SOLO
Laura Mauri, MD, professor of medicine at Harvard Medical School, Boston, reported on 146 patients with mild to moderate hypertension at 39 U.S. and European centers, all of whom were deemed anatomically suitable for device therapy on the basis of the results of renal angiography. After a 4-week antihypertensive medication washout period, by which point their average blood pressure had climbed to 150/93 mm Hg, they were randomized in single-blind fashion to endovascular ultrasound RDN using ReCor Medical’s Paradise system or to renal angiography as a sham procedure.
The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months’ follow-up post procedure in an intent-to-treat analysis. The RDN group had an 8.5–mm Hg reduction from baseline, compared with a 2.2–mm Hg reduction in sham-treated controls.
In a per protocol analysis excluding the five patients in the RDN group and 13 controls who required antihypertensive medication during the 2-month follow-up period, the average reduction in daytime ambulatory SBP was 8.5 mm Hg in the RDN group and 0.1 mm Hg in controls.
Similar statistically significant and clinically important placebo-controlled reductions in blood pressure were seen in all other endpoints, including 24-hour ambulatory, office, and home blood pressure.
“To put this in context, the magnitude of effect observed both on ambulatory blood pressure as well as office blood pressure is comparable with differences in blood pressure associated with reduction in cardiovascular events in population-based studies and meta-analyses of antihypertensive medication randomized trials,” Dr. Mauri observed.
At 2 months, 20% of the RDN group had a blood pressure below 135/85 mm Hg in the absence of antihypertensive medication, compared with 3% of controls.
No major adverse events such as renal failure, major vascular complications, embolism with end organ damage, or hypertensive crisis occurred during 2 months of follow-up. Follow-up will continue out to 3 years to evaluate the durability of therapeutic benefit.
The Paradise ultrasound system achieves circumferential ablation at a controllable depth of 1-6 mm in order to interrupt renal nerve traffic. Two or three ablations, each lasting 7 seconds, are delivered to each of the main renal arteries. The arterial wall is protected by water circulating through the balloon. The results were published simultaneously with Dr. Mauri’s presentation (Lancet 2018 May 23; doi: 10.1016/S0140-6736[18]31082-1).
SPYRAL HTN-ON MED
David E. Kandzari, MD, reported on the first 80 patients to complete 6 months of prospective follow-up in this ongoing international, single-blind, randomized trial of more than 400 patients with inadequately controlled hypertension on one to three commonly prescribed antihypertensive medications. Participants are being randomized to RDN via circumferential radiofrequency ablation using Medtronic’s Symplicity Spyral catheter or a sham control procedure. Although in this trial patients remain on their antihypertensive medications, an earlier randomized trial established proof of principle for efficacy in the absence of antihypertensive drugs.
In the real RDN group, 24-hour ambulatory blood pressure fell from baseline to 6 months of follow-up to a statistically significant and clinically meaningful degree: by 9.0 mm Hg systolic, compared with 1.6 mm Hg in controls, and by 6.0 mm Hg diastolic versus 1.9 mm Hg with the sham procedure. Similarly, office blood pressure fell by 9.4/5.2 mm Hg with RDN, compared with 2.6/1.7 mm Hg in controls.
Notably, 24-hour ambulatory systolic blood pressure was significantly lower in the RDN group around the clock.
“This may have important considerations with regard to pharmacotherapies with pharmacokinetic peaks and troughs in the early morning hours and late evening, or perhaps for groups with hypertension who are at especially high risk for cardiovascular events, such as those with nocturnal or early morning hypertension,” observed Dr. Kandzari, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute in Atlanta.
“This raises the concept of an ‘always on’ effect for renal denervation therapy that may be in distinction to pharmacotherapy and independent of adherence issues,” he added.
And speaking of adherence, a key feature of SPYRAL HTN-ON MED was that the trial incorporated periodic drug adherence monitoring using both urine and blood testing. The results, Dr. Kandzari said, were eye opening: At any given time, roughly 40% of patients in both study arms were nonadherent to their antihypertensive medications. Moreover, nonadherence was dynamic: It was not predictable for any single patient at any time point.
This 40% nonadherence rate was surprisingly high given that participants in SPYRAL HTN-ON MED were volunteers eager to participate in a non–drug treatment study and were informed up front that they would be undergoing adherence testing.
As in RADIANCE-HTN SOLO, no safety issues arose during follow-up in SPYRAL HTN-ON MED. The results were published simultaneously with Dr. Kandzari’s presentation (Lancet 2018 May 23; doi: 10.1016/S0140-6736[18]30951-6).
One difference between the two technologies is that, unlike the ReCor Paradise ultrasound catheter, which ablates in the main renal arteries, the Medtronic radiofrequency device is placed in the side branches.
Asked whether he sees RDN, provided it is established as safe and effective, being used primarily in hypertensive patients who are on or off medication, Dr. Kandzari replied that his personal view is it will have a role in both. Some patients would prefer not to take drugs. For others with uncontrolled hypertension despite multidrug therapy, RDN could serve as adjunctive therapy that reduces their need for medication.
Unanswered questions
Additional studies of both technologies are ongoing, and pivotal large phase 3 trials are being planned, with results expected in the next year or 2. Asked if regulatory agencies are going to require large, long-term trials with hard cardiovascular endpoints as a condition for approval, Dr. Mauri said a strong case can be made for bypassing this step.
“Blood pressure is remarkable,” she replied. “It’s one of the strongest surrogate endpoints that we have in the medical literature. It’s supported by multiple randomized trials of antihypertensive therapies, which have shown that reductions in blood pressure are associated with reductions in mortality from cardiovascular events. That’s really the gold standard for a surrogate endpoint. So I think it’s convincing. That being said, I would be very interested to also see hard endpoints in the long term, but that will take time.”
And time is a luxury in light of the escalating global hypertension pandemic. Dr. Mahfoud noted that it’s estimated that in 2015, 950 million people around the world had a systolic blood pressure in excess of 140 mm Hg. By 2025, that figure is expected to climb to 2.5 billion people. The Centers for Disease Control and Prevention estimates that more than 360,000 deaths per year in the United States have hypertension as the primary or a contributing cause. Blood pressure control rates remain unacceptably low, in the 50% range. Nonadherence is high. So there is a pressing unmet need for new forms of treatment.
Dr. Mahfoud cited three major remaining research priorities for RDN therapy. There is a need for some form of intraprocedural feedback to inform the interventionalist while still in the catheterization lab that the denervation is successfully completed. A reliable predictor of response is desirable so that likely nonresponders to RDN aren’t needlessly exposed to the procedure. And of course, the sustainability of benefit for RDN requires longer-term study.
Dr. Kandzari reported receiving institutional research support and consulting fees from Medtronic and several other medical device companies. Dr. Mauri reported receiving institutional research support from ReCor and other device companies and serving as a consultant to ReCor and Medtronic; in addition, she has accepted a position as a vice president at Medtronic to begin in September.
PARIS – Endovascular device–delivered renal denervation has been dramatically resuscitated as a promisingly safe and effective nonpharmacologic treatment for hypertension on the basis of two rigorous positive, prospective, sham-controlled, randomized trials presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
“These two trials are proof of concept. They were not intended to show superiority of denervation over drug therapy. They provide the proof of principle that when we interfere with the renal sympathetic nervous system we are able to lower blood pressure,” according to Felix Mahfoud, MD, an interventional cardiologist at Saarland University Hospital in Homburg, Germany, who was a coinvestigator in both trials.
As a longtime investigator in the field, he was selected by the EuroPCR 2018 organizers to present an official statement to attendees in conjunction with presentation of the two late-breaking clinical trials. The essence of the official commentary was that, despite what physicians have heard based on earlier major setbacks, renal denervation (RDN) therapy for hypertension is alive and well; it’s an active area of investigation; and it holds promise for addressing the vast unmet need for better control of hypertension.
“It’s an interesting field. EuroPCR is committed to further support of the field. Stay tuned; there’s more to come. It’s been a bumpy road up until now, but I think we’re back on track with renal denervation,” Dr. Mahfoud said.
A few years ago RDN was widely dismissed as a failed treatment strategy on the basis of the negative results of the phase 3 SYMPLICITY HTN-3 trial conducted in patients with multidrug-resistant hypertension (N Engl J Med. 2014 Apr 10;370[15]:1393-401). Since then, two European consensus conferences on device-based hypertension therapies were held in 2015 and 2017. Those meetings analyzed key mistakes in earlier research and identified three key confounders that need to be standardized in order for high-quality research to move forward: The use of antihypertensive medications, or lack thereof, must be fixed and consistent; patients with severe treatment-resistant hypertension for whom basically nothing works are not the population to study initially; and key trial design and procedural details for the various endovascular therapies in development must be agreed upon.
The two sham-controlled trials presented at EuroPCR 2018 utilized different ablative energy sources: The RADIANCE-HTN SOLO study employed an ultrasound catheter, while the SPYRAL HTN-ON MED trial used a radiofrequency device. Both devices remain investigational. Each aims to ablate both the afferent and efferent renal sympathetic nerves located in the adventitia that run to and from the brain.
RADIANCE-HTN SOLO
Laura Mauri, MD, professor of medicine at Harvard Medical School, Boston, reported on 146 patients with mild to moderate hypertension at 39 U.S. and European centers, all of whom were deemed anatomically suitable for device therapy on the basis of the results of renal angiography. After a 4-week antihypertensive medication washout period, by which point their average blood pressure had climbed to 150/93 mm Hg, they were randomized in single-blind fashion to endovascular ultrasound RDN using ReCor Medical’s Paradise system or to renal angiography as a sham procedure.
The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months’ follow-up post procedure in an intent-to-treat analysis. The RDN group had an 8.5–mm Hg reduction from baseline, compared with a 2.2–mm Hg reduction in sham-treated controls.
In a per protocol analysis excluding the five patients in the RDN group and 13 controls who required antihypertensive medication during the 2-month follow-up period, the average reduction in daytime ambulatory SBP was 8.5 mm Hg in the RDN group and 0.1 mm Hg in controls.
Similar statistically significant and clinically important placebo-controlled reductions in blood pressure were seen in all other endpoints, including 24-hour ambulatory, office, and home blood pressure.
“To put this in context, the magnitude of effect observed both on ambulatory blood pressure as well as office blood pressure is comparable with differences in blood pressure associated with reduction in cardiovascular events in population-based studies and meta-analyses of antihypertensive medication randomized trials,” Dr. Mauri observed.
At 2 months, 20% of the RDN group had a blood pressure below 135/85 mm Hg in the absence of antihypertensive medication, compared with 3% of controls.
No major adverse events such as renal failure, major vascular complications, embolism with end organ damage, or hypertensive crisis occurred during 2 months of follow-up. Follow-up will continue out to 3 years to evaluate the durability of therapeutic benefit.
The Paradise ultrasound system achieves circumferential ablation at a controllable depth of 1-6 mm in order to interrupt renal nerve traffic. Two or three ablations, each lasting 7 seconds, are delivered to each of the main renal arteries. The arterial wall is protected by water circulating through the balloon. The results were published simultaneously with Dr. Mauri’s presentation (Lancet 2018 May 23; doi: 10.1016/S0140-6736[18]31082-1).
SPYRAL HTN-ON MED
David E. Kandzari, MD, reported on the first 80 patients to complete 6 months of prospective follow-up in this ongoing international, single-blind, randomized trial of more than 400 patients with inadequately controlled hypertension on one to three commonly prescribed antihypertensive medications. Participants are being randomized to RDN via circumferential radiofrequency ablation using Medtronic’s Symplicity Spyral catheter or a sham control procedure. Although in this trial patients remain on their antihypertensive medications, an earlier randomized trial established proof of principle for efficacy in the absence of antihypertensive drugs.
In the real RDN group, 24-hour ambulatory blood pressure fell from baseline to 6 months of follow-up to a statistically significant and clinically meaningful degree: by 9.0 mm Hg systolic, compared with 1.6 mm Hg in controls, and by 6.0 mm Hg diastolic versus 1.9 mm Hg with the sham procedure. Similarly, office blood pressure fell by 9.4/5.2 mm Hg with RDN, compared with 2.6/1.7 mm Hg in controls.
Notably, 24-hour ambulatory systolic blood pressure was significantly lower in the RDN group around the clock.
“This may have important considerations with regard to pharmacotherapies with pharmacokinetic peaks and troughs in the early morning hours and late evening, or perhaps for groups with hypertension who are at especially high risk for cardiovascular events, such as those with nocturnal or early morning hypertension,” observed Dr. Kandzari, director of interventional cardiology and chief scientific officer at the Piedmont Heart Institute in Atlanta.
“This raises the concept of an ‘always on’ effect for renal denervation therapy that may be in distinction to pharmacotherapy and independent of adherence issues,” he added.
And speaking of adherence, a key feature of SPYRAL HTN-ON MED was that the trial incorporated periodic drug adherence monitoring using both urine and blood testing. The results, Dr. Kandzari said, were eye opening: At any given time, roughly 40% of patients in both study arms were nonadherent to their antihypertensive medications. Moreover, nonadherence was dynamic: It was not predictable for any single patient at any time point.
This 40% nonadherence rate was surprisingly high given that participants in SPYRAL HTN-ON MED were volunteers eager to participate in a non–drug treatment study and were informed up front that they would be undergoing adherence testing.
As in RADIANCE-HTN SOLO, no safety issues arose during follow-up in SPYRAL HTN-ON MED. The results were published simultaneously with Dr. Kandzari’s presentation (Lancet 2018 May 23; doi: 10.1016/S0140-6736[18]30951-6).
One difference between the two technologies is that, unlike the ReCor Paradise ultrasound catheter, which ablates in the main renal arteries, the Medtronic radiofrequency device is placed in the side branches.
Asked whether he sees RDN, provided it is established as safe and effective, being used primarily in hypertensive patients who are on or off medication, Dr. Kandzari replied that his personal view is it will have a role in both. Some patients would prefer not to take drugs. For others with uncontrolled hypertension despite multidrug therapy, RDN could serve as adjunctive therapy that reduces their need for medication.
Unanswered questions
Additional studies of both technologies are ongoing, and pivotal large phase 3 trials are being planned, with results expected in the next year or 2. Asked if regulatory agencies are going to require large, long-term trials with hard cardiovascular endpoints as a condition for approval, Dr. Mauri said a strong case can be made for bypassing this step.
“Blood pressure is remarkable,” she replied. “It’s one of the strongest surrogate endpoints that we have in the medical literature. It’s supported by multiple randomized trials of antihypertensive therapies, which have shown that reductions in blood pressure are associated with reductions in mortality from cardiovascular events. That’s really the gold standard for a surrogate endpoint. So I think it’s convincing. That being said, I would be very interested to also see hard endpoints in the long term, but that will take time.”
And time is a luxury in light of the escalating global hypertension pandemic. Dr. Mahfoud noted that it’s estimated that in 2015, 950 million people around the world had a systolic blood pressure in excess of 140 mm Hg. By 2025, that figure is expected to climb to 2.5 billion people. The Centers for Disease Control and Prevention estimates that more than 360,000 deaths per year in the United States have hypertension as the primary or a contributing cause. Blood pressure control rates remain unacceptably low, in the 50% range. Nonadherence is high. So there is a pressing unmet need for new forms of treatment.
Dr. Mahfoud cited three major remaining research priorities for RDN therapy. There is a need for some form of intraprocedural feedback to inform the interventionalist while still in the catheterization lab that the denervation is successfully completed. A reliable predictor of response is desirable so that likely nonresponders to RDN aren’t needlessly exposed to the procedure. And of course, the sustainability of benefit for RDN requires longer-term study.
Dr. Kandzari reported receiving institutional research support and consulting fees from Medtronic and several other medical device companies. Dr. Mauri reported receiving institutional research support from ReCor and other device companies and serving as a consultant to ReCor and Medtronic; in addition, she has accepted a position as a vice president at Medtronic to begin in September.
REPORTING FROM EUROPCR 2018