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Renal denervation for hypertension rebounds
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
High testosterone in postmenopausal women may add CVD risk
In postmenopausal women, a higher level of testosterone in comparison to estrogen may increase the cardiovascular disease risk later in life, results of a recent analysis suggest.
A higher ratio of testosterone to estradiol was associated with the development of cardiovascular disease, coronary heart disease, and heart failure in postmenopausal women, according to results from an analysis based on 2,834 postmenopausal women in MESA (Multi-Ethnic Study of Atherosclerosis).
In addition, total testosterone levels were associated with increased cardiovascular disease and coronary heart disease, while estradiol is associated with a reduced risk of coronary heart disease and heart failure with reduced ejection fraction, investigators reported in the Journal of the American College of Cardiology.
Without any interventional studies as guidance, it’s not clear what the “best strategy” would be to modify sex hormone levels and reduce cardiovascular disease risk, wrote investigator Di Zhao, PhD, of the department of epidemiology at Johns Hopkins University Bloomberg School of Public Health, Baltimore, and her study coauthors.
“Nonetheless, a more androgenic sex hormone profile may identify a woman at higher risk for cardiovascular disease who may benefit from other risk-reducing strategies,” Dr. Zhao and her colleagues wrote in their report.
The postmenopausal women included in this analysis all had baseline measurements of testosterone, estradiol, dehydroepiandrosterone, and sex hormone–binding globulin levels between 2000 and 2002, according to the report.
After more than 12 years of follow-up, investigators found that a higher total testosterone to estradiol ratio was independently associated with an increased risk of incident cardiovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.02-1.40), coronary heart disease (HR, 1.45; 95% CI, 1.19-1.78), and heart failure (HR, 1.31; 95% CI, 1.01-1.70).
Investigators also reported a statistically significant association between total testosterone levels and risk of cardiovascular disease and coronary heart disease but not risk of heart failure.
In a subgroup analysis of postmenopausal women with heart failure, investigators found a significant positive association with the testosterone to estradiol ratio (HR, 1.65; 95% CI, 1.07-2.54) and inverse associations for estradiol (HR, 0.60; 95% CI, 0.39-0.93) and for dehydroepiandrosterone (HR, 0.59; 95% CI, 0.44-0.78).
On their own, estradiol levels had no association with cardiovascular disease events overall, but they were associated with lower coronary heart disease risk, according to investigators. Estradiol also was associated with a lower heart failure risk, though the trend did not reach statistical significance.
The study was partially funded by the American Heart Association’s Go Red for Women Research Network. Study authors reported disclosures related to Cordex Systems, Siemens Diagnostics, and other entities.
SOURCE: Zhao D et al. J Am Coll Cardiol. 2018 Jun 5; 71:2555-66.
This study offers new insights into the relationships between endogenous hormones and how they influence cardiovascular event risk, according to Virginia M. Miller, PhD, and Rekha Mankad, MD.
Previous observational studies have established that decreases in endogenous estrogen led to increases in cardiovascular event risk and incidence, Dr. Miller and Dr. Mankad said in an editorial referencing the study.
What’s less clear is the role of testosterone in cardiovascular risk and event incidence, both by itself and in relation to other endogenous hormones.
“Few studies have gone beyond singular associations of hormone levels with cardiovascular events,” the editorial authors wrote in the Journal of the American College of Cardiology.
The study by Zhao and her colleagues is unique in part because their analysis considers the ratio of testosterone to estradiol. In particular, they found that a higher testosterone to estradiol level was associated with a higher incidence of cardiovascular events overall and of coronary heart disease.
What was unexpected, according to Dr. Miller and Dr. Mankad, was a U-shaped association with incident heart failure. In subgroup analysis, investigators found a positive association between testosterone to estradiol ratio and heart failure with reduced ejection fraction but not with heart failure with preserved ejection fraction.
“By addressing a set of defined incident events, this study provides new information needed to develop mechanistic hypotheses of causal relationships of hormones with specific aspects of cardiac function,” the editorial authors wrote.
Dr. Miller and Dr. Mankad are both with the women’s health research center and department of cardiovascular disease at the Women’s Heart Clinic at the Mayo Clinic, Rochester, Minn. These comments are derived from their editorial in the Journal of the American College of Cardiology. Dr. Mankad had no disclosures, while Dr. Miller reported support from a National Institutes of Health grant.
This study offers new insights into the relationships between endogenous hormones and how they influence cardiovascular event risk, according to Virginia M. Miller, PhD, and Rekha Mankad, MD.
Previous observational studies have established that decreases in endogenous estrogen led to increases in cardiovascular event risk and incidence, Dr. Miller and Dr. Mankad said in an editorial referencing the study.
What’s less clear is the role of testosterone in cardiovascular risk and event incidence, both by itself and in relation to other endogenous hormones.
“Few studies have gone beyond singular associations of hormone levels with cardiovascular events,” the editorial authors wrote in the Journal of the American College of Cardiology.
The study by Zhao and her colleagues is unique in part because their analysis considers the ratio of testosterone to estradiol. In particular, they found that a higher testosterone to estradiol level was associated with a higher incidence of cardiovascular events overall and of coronary heart disease.
What was unexpected, according to Dr. Miller and Dr. Mankad, was a U-shaped association with incident heart failure. In subgroup analysis, investigators found a positive association between testosterone to estradiol ratio and heart failure with reduced ejection fraction but not with heart failure with preserved ejection fraction.
“By addressing a set of defined incident events, this study provides new information needed to develop mechanistic hypotheses of causal relationships of hormones with specific aspects of cardiac function,” the editorial authors wrote.
Dr. Miller and Dr. Mankad are both with the women’s health research center and department of cardiovascular disease at the Women’s Heart Clinic at the Mayo Clinic, Rochester, Minn. These comments are derived from their editorial in the Journal of the American College of Cardiology. Dr. Mankad had no disclosures, while Dr. Miller reported support from a National Institutes of Health grant.
This study offers new insights into the relationships between endogenous hormones and how they influence cardiovascular event risk, according to Virginia M. Miller, PhD, and Rekha Mankad, MD.
Previous observational studies have established that decreases in endogenous estrogen led to increases in cardiovascular event risk and incidence, Dr. Miller and Dr. Mankad said in an editorial referencing the study.
What’s less clear is the role of testosterone in cardiovascular risk and event incidence, both by itself and in relation to other endogenous hormones.
“Few studies have gone beyond singular associations of hormone levels with cardiovascular events,” the editorial authors wrote in the Journal of the American College of Cardiology.
The study by Zhao and her colleagues is unique in part because their analysis considers the ratio of testosterone to estradiol. In particular, they found that a higher testosterone to estradiol level was associated with a higher incidence of cardiovascular events overall and of coronary heart disease.
What was unexpected, according to Dr. Miller and Dr. Mankad, was a U-shaped association with incident heart failure. In subgroup analysis, investigators found a positive association between testosterone to estradiol ratio and heart failure with reduced ejection fraction but not with heart failure with preserved ejection fraction.
“By addressing a set of defined incident events, this study provides new information needed to develop mechanistic hypotheses of causal relationships of hormones with specific aspects of cardiac function,” the editorial authors wrote.
Dr. Miller and Dr. Mankad are both with the women’s health research center and department of cardiovascular disease at the Women’s Heart Clinic at the Mayo Clinic, Rochester, Minn. These comments are derived from their editorial in the Journal of the American College of Cardiology. Dr. Mankad had no disclosures, while Dr. Miller reported support from a National Institutes of Health grant.
In postmenopausal women, a higher level of testosterone in comparison to estrogen may increase the cardiovascular disease risk later in life, results of a recent analysis suggest.
A higher ratio of testosterone to estradiol was associated with the development of cardiovascular disease, coronary heart disease, and heart failure in postmenopausal women, according to results from an analysis based on 2,834 postmenopausal women in MESA (Multi-Ethnic Study of Atherosclerosis).
In addition, total testosterone levels were associated with increased cardiovascular disease and coronary heart disease, while estradiol is associated with a reduced risk of coronary heart disease and heart failure with reduced ejection fraction, investigators reported in the Journal of the American College of Cardiology.
Without any interventional studies as guidance, it’s not clear what the “best strategy” would be to modify sex hormone levels and reduce cardiovascular disease risk, wrote investigator Di Zhao, PhD, of the department of epidemiology at Johns Hopkins University Bloomberg School of Public Health, Baltimore, and her study coauthors.
“Nonetheless, a more androgenic sex hormone profile may identify a woman at higher risk for cardiovascular disease who may benefit from other risk-reducing strategies,” Dr. Zhao and her colleagues wrote in their report.
The postmenopausal women included in this analysis all had baseline measurements of testosterone, estradiol, dehydroepiandrosterone, and sex hormone–binding globulin levels between 2000 and 2002, according to the report.
After more than 12 years of follow-up, investigators found that a higher total testosterone to estradiol ratio was independently associated with an increased risk of incident cardiovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.02-1.40), coronary heart disease (HR, 1.45; 95% CI, 1.19-1.78), and heart failure (HR, 1.31; 95% CI, 1.01-1.70).
Investigators also reported a statistically significant association between total testosterone levels and risk of cardiovascular disease and coronary heart disease but not risk of heart failure.
In a subgroup analysis of postmenopausal women with heart failure, investigators found a significant positive association with the testosterone to estradiol ratio (HR, 1.65; 95% CI, 1.07-2.54) and inverse associations for estradiol (HR, 0.60; 95% CI, 0.39-0.93) and for dehydroepiandrosterone (HR, 0.59; 95% CI, 0.44-0.78).
On their own, estradiol levels had no association with cardiovascular disease events overall, but they were associated with lower coronary heart disease risk, according to investigators. Estradiol also was associated with a lower heart failure risk, though the trend did not reach statistical significance.
The study was partially funded by the American Heart Association’s Go Red for Women Research Network. Study authors reported disclosures related to Cordex Systems, Siemens Diagnostics, and other entities.
SOURCE: Zhao D et al. J Am Coll Cardiol. 2018 Jun 5; 71:2555-66.
In postmenopausal women, a higher level of testosterone in comparison to estrogen may increase the cardiovascular disease risk later in life, results of a recent analysis suggest.
A higher ratio of testosterone to estradiol was associated with the development of cardiovascular disease, coronary heart disease, and heart failure in postmenopausal women, according to results from an analysis based on 2,834 postmenopausal women in MESA (Multi-Ethnic Study of Atherosclerosis).
In addition, total testosterone levels were associated with increased cardiovascular disease and coronary heart disease, while estradiol is associated with a reduced risk of coronary heart disease and heart failure with reduced ejection fraction, investigators reported in the Journal of the American College of Cardiology.
Without any interventional studies as guidance, it’s not clear what the “best strategy” would be to modify sex hormone levels and reduce cardiovascular disease risk, wrote investigator Di Zhao, PhD, of the department of epidemiology at Johns Hopkins University Bloomberg School of Public Health, Baltimore, and her study coauthors.
“Nonetheless, a more androgenic sex hormone profile may identify a woman at higher risk for cardiovascular disease who may benefit from other risk-reducing strategies,” Dr. Zhao and her colleagues wrote in their report.
The postmenopausal women included in this analysis all had baseline measurements of testosterone, estradiol, dehydroepiandrosterone, and sex hormone–binding globulin levels between 2000 and 2002, according to the report.
After more than 12 years of follow-up, investigators found that a higher total testosterone to estradiol ratio was independently associated with an increased risk of incident cardiovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.02-1.40), coronary heart disease (HR, 1.45; 95% CI, 1.19-1.78), and heart failure (HR, 1.31; 95% CI, 1.01-1.70).
Investigators also reported a statistically significant association between total testosterone levels and risk of cardiovascular disease and coronary heart disease but not risk of heart failure.
In a subgroup analysis of postmenopausal women with heart failure, investigators found a significant positive association with the testosterone to estradiol ratio (HR, 1.65; 95% CI, 1.07-2.54) and inverse associations for estradiol (HR, 0.60; 95% CI, 0.39-0.93) and for dehydroepiandrosterone (HR, 0.59; 95% CI, 0.44-0.78).
On their own, estradiol levels had no association with cardiovascular disease events overall, but they were associated with lower coronary heart disease risk, according to investigators. Estradiol also was associated with a lower heart failure risk, though the trend did not reach statistical significance.
The study was partially funded by the American Heart Association’s Go Red for Women Research Network. Study authors reported disclosures related to Cordex Systems, Siemens Diagnostics, and other entities.
SOURCE: Zhao D et al. J Am Coll Cardiol. 2018 Jun 5; 71:2555-66.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Key clinical point: Levels of testosterone and estradiol after menopause correlated with increased cardiovascular risks later in life.
Major finding: A higher total testosterone to estradiol ratio was independently associated with increased risk of incident cardiovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.02-1.40).
Study details: Analysis including 2,834 postmenopausal women in the MESA (Multi-Ethnic Study of Atherosclerosis) study.
Disclosures: Partial funding came from the American Heart Association’s Go Red for Women Research Network. Study authors reported disclosures related to Cordex Systems, Siemens Diagnostics, and other entities.
Source: Zhao D et al. J Am Coll Cardiol. 2018 Jun 5; 71:2555-66.
Which Factors Predict Successful Epilepsy Reoperations?
LOS ANGELES—Among patients with intractable focal epilepsy who have failed one or more epilepsy surgeries, reoperation may provide long-term seizure control, according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Patients with prior epilepsy surgery are less likely to achieve seizure freedom, however, compared with patients undergoing initial epilepsy surgery, the researchers said.
“It is possible to achieve long-term seizure control in patients with failed prior epilepsy surgery,” said Ruta Yardi, MD, a researcher at the Cleveland Clinic, and colleagues. “A lesional MRI, specific prior postoperative pathology, and fewer prior resections seem to predict better outcomes.” These results may be helpful in identifying candidates for reoperation, the investigators said.
Epilepsy surgery is the most effective treatment option for patients with medically refractory focal epilepsy, but initial surgeries may not be successful, Dr. Yardi and colleagues said. A small percentage of patients who do not benefit from a first surgery may be evaluated for another resection. Data for how outcomes vary with successive surgeries are limited, however, the researchers said.
To assess longitudinal seizure outcomes following reoperations in patients with intractable focal epilepsy and identify prognostic factors that influence these outcomes, Dr. Yardi and colleagues retrospectively studied 898 patients (448 female; about a third pediatric) who underwent epilepsy surgery at the Cleveland Clinic between 1995 and 2016. The investigators analyzed baseline characteristics, known predictors of seizure outcome, surgical data, pathology, and postoperative seizure recurrence. The primary outcome was complete seizure freedom (ie, Engel Class IA) at last follow-up.
The researchers analyzed the data using Kaplan–Meier survival curves and univariate and multivariate hazard modeling. The analysis included 788 patients without prior surgery, 92 patients with one prior surgery, and 18 patients with two or more prior surgeries. Two years after the most recent epilepsy surgery, 58% of patients with no prior surgery were seizure-free, compared with 49% of patients who had one prior surgery and 39% of patients who had two or more prior surgeries. Patients with more than one surgery were more likely to have an Engel outcome score of greater than Class I.
Variables that correlated with better seizu
—Jake Remaly
LOS ANGELES—Among patients with intractable focal epilepsy who have failed one or more epilepsy surgeries, reoperation may provide long-term seizure control, according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Patients with prior epilepsy surgery are less likely to achieve seizure freedom, however, compared with patients undergoing initial epilepsy surgery, the researchers said.
“It is possible to achieve long-term seizure control in patients with failed prior epilepsy surgery,” said Ruta Yardi, MD, a researcher at the Cleveland Clinic, and colleagues. “A lesional MRI, specific prior postoperative pathology, and fewer prior resections seem to predict better outcomes.” These results may be helpful in identifying candidates for reoperation, the investigators said.
Epilepsy surgery is the most effective treatment option for patients with medically refractory focal epilepsy, but initial surgeries may not be successful, Dr. Yardi and colleagues said. A small percentage of patients who do not benefit from a first surgery may be evaluated for another resection. Data for how outcomes vary with successive surgeries are limited, however, the researchers said.
To assess longitudinal seizure outcomes following reoperations in patients with intractable focal epilepsy and identify prognostic factors that influence these outcomes, Dr. Yardi and colleagues retrospectively studied 898 patients (448 female; about a third pediatric) who underwent epilepsy surgery at the Cleveland Clinic between 1995 and 2016. The investigators analyzed baseline characteristics, known predictors of seizure outcome, surgical data, pathology, and postoperative seizure recurrence. The primary outcome was complete seizure freedom (ie, Engel Class IA) at last follow-up.
The researchers analyzed the data using Kaplan–Meier survival curves and univariate and multivariate hazard modeling. The analysis included 788 patients without prior surgery, 92 patients with one prior surgery, and 18 patients with two or more prior surgeries. Two years after the most recent epilepsy surgery, 58% of patients with no prior surgery were seizure-free, compared with 49% of patients who had one prior surgery and 39% of patients who had two or more prior surgeries. Patients with more than one surgery were more likely to have an Engel outcome score of greater than Class I.
Variables that correlated with better seizu
—Jake Remaly
LOS ANGELES—Among patients with intractable focal epilepsy who have failed one or more epilepsy surgeries, reoperation may provide long-term seizure control, according to research presented at the 70th Annual Meeting of the American Academy of Neurology. Patients with prior epilepsy surgery are less likely to achieve seizure freedom, however, compared with patients undergoing initial epilepsy surgery, the researchers said.
“It is possible to achieve long-term seizure control in patients with failed prior epilepsy surgery,” said Ruta Yardi, MD, a researcher at the Cleveland Clinic, and colleagues. “A lesional MRI, specific prior postoperative pathology, and fewer prior resections seem to predict better outcomes.” These results may be helpful in identifying candidates for reoperation, the investigators said.
Epilepsy surgery is the most effective treatment option for patients with medically refractory focal epilepsy, but initial surgeries may not be successful, Dr. Yardi and colleagues said. A small percentage of patients who do not benefit from a first surgery may be evaluated for another resection. Data for how outcomes vary with successive surgeries are limited, however, the researchers said.
To assess longitudinal seizure outcomes following reoperations in patients with intractable focal epilepsy and identify prognostic factors that influence these outcomes, Dr. Yardi and colleagues retrospectively studied 898 patients (448 female; about a third pediatric) who underwent epilepsy surgery at the Cleveland Clinic between 1995 and 2016. The investigators analyzed baseline characteristics, known predictors of seizure outcome, surgical data, pathology, and postoperative seizure recurrence. The primary outcome was complete seizure freedom (ie, Engel Class IA) at last follow-up.
The researchers analyzed the data using Kaplan–Meier survival curves and univariate and multivariate hazard modeling. The analysis included 788 patients without prior surgery, 92 patients with one prior surgery, and 18 patients with two or more prior surgeries. Two years after the most recent epilepsy surgery, 58% of patients with no prior surgery were seizure-free, compared with 49% of patients who had one prior surgery and 39% of patients who had two or more prior surgeries. Patients with more than one surgery were more likely to have an Engel outcome score of greater than Class I.
Variables that correlated with better seizu
—Jake Remaly
Effects of psoriatic arthritis not just physical
conducted by the Harris Poll on behalf of Pfizer.
Over 90% of respondents said that their psoriatic arthritis had negatively impacted their emotional and mental well-being and 75% reported negative effects on their relationships with friends and family, Pfizer reported. Among the 301 adults aged 18 years and older who responded to the survey, 58% had stopped participating in sports or recreational activities and 51% had stopped participating in social activities.
The effects on patients’ professional lives also were considerable: Almost 74% said that it had a negative effect on their career path, 41% had experienced decreased productivity, and 13% had quit or been let go from a job, Pfizer said.
Some of the survey results suggested a disconnect between patients and their physicians. Of the 89% of patients who were very or somewhat satisfied with their prescription medication, 90% said that they would like to make changes to their treatment regimen and 89% described their illness as moderate to severe, Pfizer reported.
The survey was conducted online from Nov. 2 to Dec. 1, 2017.
conducted by the Harris Poll on behalf of Pfizer.
Over 90% of respondents said that their psoriatic arthritis had negatively impacted their emotional and mental well-being and 75% reported negative effects on their relationships with friends and family, Pfizer reported. Among the 301 adults aged 18 years and older who responded to the survey, 58% had stopped participating in sports or recreational activities and 51% had stopped participating in social activities.
The effects on patients’ professional lives also were considerable: Almost 74% said that it had a negative effect on their career path, 41% had experienced decreased productivity, and 13% had quit or been let go from a job, Pfizer said.
Some of the survey results suggested a disconnect between patients and their physicians. Of the 89% of patients who were very or somewhat satisfied with their prescription medication, 90% said that they would like to make changes to their treatment regimen and 89% described their illness as moderate to severe, Pfizer reported.
The survey was conducted online from Nov. 2 to Dec. 1, 2017.
conducted by the Harris Poll on behalf of Pfizer.
Over 90% of respondents said that their psoriatic arthritis had negatively impacted their emotional and mental well-being and 75% reported negative effects on their relationships with friends and family, Pfizer reported. Among the 301 adults aged 18 years and older who responded to the survey, 58% had stopped participating in sports or recreational activities and 51% had stopped participating in social activities.
The effects on patients’ professional lives also were considerable: Almost 74% said that it had a negative effect on their career path, 41% had experienced decreased productivity, and 13% had quit or been let go from a job, Pfizer said.
Some of the survey results suggested a disconnect between patients and their physicians. Of the 89% of patients who were very or somewhat satisfied with their prescription medication, 90% said that they would like to make changes to their treatment regimen and 89% described their illness as moderate to severe, Pfizer reported.
The survey was conducted online from Nov. 2 to Dec. 1, 2017.
Ubrogepant May Treat Acute Migraine Attacks Effectively
LOS ANGELES—Ubrogepant may relieve the pain of acute migraine attacks, as well as other bothersome migraine-related symptoms, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The drug is well-tolerated and does not raise significant safety concerns, according to the researchers.
Ubrogepant is a novel, oral antagonist of the calcitonin gene-related peptide (CGRP) receptor that Allergan is developing for the acute treatment of migraine. Joel Trugman, MD, Director of Clinical Development for Allergan, and colleagues conducted a phase III study to examine the efficacy, safety, and tolerability of ubrogepant, compared with placebo, for the acute treatment of a single migraine attack.
Assessing Two Doses of Ubrogepant
In this multicenter, double-blind, parallel-group study, adult patients with a history of migraine with or without aura were randomized in equal groups to placebo, 50 mg of ubrogepant, or 100 mg of ubrogepant. Patients had as many as 60 days to treat a single migraine attack of moderate or severe headache pain intensity. The study’s two primary efficacy end points were pain freedom at two hours after initial dose and absence of the most bothersome migraine-associated symptom (MBS) at two hours after initial dose. Participants identified the MBS at the time of the treated attack. The investigators also assessed ubrogepant’s safety and tolerability.
Dr. Trugman and colleagues randomized 1,672 patients. Of this population, 1,436 participants were included in the safety population, and 1,327 were included in the modified-intention-to-treat efficacy analysis. The latter efficacy analysis included patients who received one or more dose of ubrogepant, recorded baseline headache severity, and recorded one or more postdose headache severity or MBS measurement at or before two hours.
Ubrogepant Was Superior to Placebo
The population’s mean age was 40.7. Most participants were Caucasian (82.4%) and female (87.5%). The MBS identified at the time of treatment were photophobia (56.4%), phonophobia (22.3%), and nausea (20.9%). At two hours after the initial dose, the percentage of patients achieving pain freedom was 19.2% for the 50-mg group, 21.2% for the 100-mg group, and 11.8% for controls. The percentage of patients achieving absence of MBS was 38.6% for the 50-mg group, 37.7% for the 100-mg group, and 27.8% for controls. The differences between the active and control groups were statistically significant for both end points.
Ubrogepant also yielded significantly improved results on secondary end points, compared with placebo. Approximately 61% of patients who took ubrogepant achieved pain relief at two hours, compared with 49% of controls. About 36% of patients in the 50-mg group and 38% of patients in the 100-mg group achieved sustained pain relief at two to 24 hours, compared with 21% of controls. In addition, the 100-mg dose of ubrogepant yielded statistically significant differences on sustained pain freedom at two to 24 hours and on absence of photophobia at two hours, compared with placebo.
The adverse-event profile of ubrogepant was similar to that of placebo. The most common adverse events within 48 hours of dosing were nausea, somnolence, and dry mouth. The incidence of each of these adverse events was less than 5%.
This study was supported by Allergan.
LOS ANGELES—Ubrogepant may relieve the pain of acute migraine attacks, as well as other bothersome migraine-related symptoms, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The drug is well-tolerated and does not raise significant safety concerns, according to the researchers.
Ubrogepant is a novel, oral antagonist of the calcitonin gene-related peptide (CGRP) receptor that Allergan is developing for the acute treatment of migraine. Joel Trugman, MD, Director of Clinical Development for Allergan, and colleagues conducted a phase III study to examine the efficacy, safety, and tolerability of ubrogepant, compared with placebo, for the acute treatment of a single migraine attack.
Assessing Two Doses of Ubrogepant
In this multicenter, double-blind, parallel-group study, adult patients with a history of migraine with or without aura were randomized in equal groups to placebo, 50 mg of ubrogepant, or 100 mg of ubrogepant. Patients had as many as 60 days to treat a single migraine attack of moderate or severe headache pain intensity. The study’s two primary efficacy end points were pain freedom at two hours after initial dose and absence of the most bothersome migraine-associated symptom (MBS) at two hours after initial dose. Participants identified the MBS at the time of the treated attack. The investigators also assessed ubrogepant’s safety and tolerability.
Dr. Trugman and colleagues randomized 1,672 patients. Of this population, 1,436 participants were included in the safety population, and 1,327 were included in the modified-intention-to-treat efficacy analysis. The latter efficacy analysis included patients who received one or more dose of ubrogepant, recorded baseline headache severity, and recorded one or more postdose headache severity or MBS measurement at or before two hours.
Ubrogepant Was Superior to Placebo
The population’s mean age was 40.7. Most participants were Caucasian (82.4%) and female (87.5%). The MBS identified at the time of treatment were photophobia (56.4%), phonophobia (22.3%), and nausea (20.9%). At two hours after the initial dose, the percentage of patients achieving pain freedom was 19.2% for the 50-mg group, 21.2% for the 100-mg group, and 11.8% for controls. The percentage of patients achieving absence of MBS was 38.6% for the 50-mg group, 37.7% for the 100-mg group, and 27.8% for controls. The differences between the active and control groups were statistically significant for both end points.
Ubrogepant also yielded significantly improved results on secondary end points, compared with placebo. Approximately 61% of patients who took ubrogepant achieved pain relief at two hours, compared with 49% of controls. About 36% of patients in the 50-mg group and 38% of patients in the 100-mg group achieved sustained pain relief at two to 24 hours, compared with 21% of controls. In addition, the 100-mg dose of ubrogepant yielded statistically significant differences on sustained pain freedom at two to 24 hours and on absence of photophobia at two hours, compared with placebo.
The adverse-event profile of ubrogepant was similar to that of placebo. The most common adverse events within 48 hours of dosing were nausea, somnolence, and dry mouth. The incidence of each of these adverse events was less than 5%.
This study was supported by Allergan.
LOS ANGELES—Ubrogepant may relieve the pain of acute migraine attacks, as well as other bothersome migraine-related symptoms, according to data presented at the 70th Annual Meeting of the American Academy of Neurology. The drug is well-tolerated and does not raise significant safety concerns, according to the researchers.
Ubrogepant is a novel, oral antagonist of the calcitonin gene-related peptide (CGRP) receptor that Allergan is developing for the acute treatment of migraine. Joel Trugman, MD, Director of Clinical Development for Allergan, and colleagues conducted a phase III study to examine the efficacy, safety, and tolerability of ubrogepant, compared with placebo, for the acute treatment of a single migraine attack.
Assessing Two Doses of Ubrogepant
In this multicenter, double-blind, parallel-group study, adult patients with a history of migraine with or without aura were randomized in equal groups to placebo, 50 mg of ubrogepant, or 100 mg of ubrogepant. Patients had as many as 60 days to treat a single migraine attack of moderate or severe headache pain intensity. The study’s two primary efficacy end points were pain freedom at two hours after initial dose and absence of the most bothersome migraine-associated symptom (MBS) at two hours after initial dose. Participants identified the MBS at the time of the treated attack. The investigators also assessed ubrogepant’s safety and tolerability.
Dr. Trugman and colleagues randomized 1,672 patients. Of this population, 1,436 participants were included in the safety population, and 1,327 were included in the modified-intention-to-treat efficacy analysis. The latter efficacy analysis included patients who received one or more dose of ubrogepant, recorded baseline headache severity, and recorded one or more postdose headache severity or MBS measurement at or before two hours.
Ubrogepant Was Superior to Placebo
The population’s mean age was 40.7. Most participants were Caucasian (82.4%) and female (87.5%). The MBS identified at the time of treatment were photophobia (56.4%), phonophobia (22.3%), and nausea (20.9%). At two hours after the initial dose, the percentage of patients achieving pain freedom was 19.2% for the 50-mg group, 21.2% for the 100-mg group, and 11.8% for controls. The percentage of patients achieving absence of MBS was 38.6% for the 50-mg group, 37.7% for the 100-mg group, and 27.8% for controls. The differences between the active and control groups were statistically significant for both end points.
Ubrogepant also yielded significantly improved results on secondary end points, compared with placebo. Approximately 61% of patients who took ubrogepant achieved pain relief at two hours, compared with 49% of controls. About 36% of patients in the 50-mg group and 38% of patients in the 100-mg group achieved sustained pain relief at two to 24 hours, compared with 21% of controls. In addition, the 100-mg dose of ubrogepant yielded statistically significant differences on sustained pain freedom at two to 24 hours and on absence of photophobia at two hours, compared with placebo.
The adverse-event profile of ubrogepant was similar to that of placebo. The most common adverse events within 48 hours of dosing were nausea, somnolence, and dry mouth. The incidence of each of these adverse events was less than 5%.
This study was supported by Allergan.
Opioids still overprescribed for postop pain management
Most patients use far less opioids than they are prescribed after hernia and other abdominal surgery, resulting in substantial waste and potential diversion, a prospective cohort study has found.
In an evaluation of 176 narcotic-naive patients who underwent surgery in a over the 14-day postdischarge study period was 30 morphine milligram equivalents (MME) but the median prescription was 150 MME, reported Wen Hui Tan, MD, and her research team at Washington University, St. Louis. The report was published in the Journal of the American College of Surgeons.
Overall, 76.7% of patients reported being satisfied or very satisfied with their postoperative pain management. Some patients (n = 31, 17.6%) reported not filling their prescription or not taking any of their prescribed opioid pain medications at all.
Sixty-nine percent of the surgeries were laparoscopic. A variety of abdominal procedures were represented, including hiatal hernia repair, inguinal hernia repair, and cholecystectomy. The median age was 60 years. Of postoperative pain prescriptions, 67% were for hydrocodone-acetaminophen and most of the remainder were for oxycodone-acetaminophen or oxycodone alone. The median prescription was for the equivalent of 20 5-mg oxycodone pills, while the median consumption in the first 7 postoperative days was 3.7 pills. Only 4.5% of patients received a refill.
The findings are consistent with numerous studies of different types of operations showing that patients often don’t use all of the opioid medications they are prescribed for pain control after surgery.
“Now that opioid pain medications can no longer be refilled with a pharmacy via telephone, overprescription may also be partially driven by a desire to prevent future inconvenience and workload of office staff from patients requesting refills. However, the rising numbers of opioid-related unintentional deaths over the last decade point to the fact that overprescription has serious potential consequences,” the researchers wrote.
They reported having no potential conflicts of interest.
SOURCE: Tan et al. J Am Coll Surg 2018 May 7. doi: 10.1016/j.jamcollsurg.2018.04.032.
Most patients use far less opioids than they are prescribed after hernia and other abdominal surgery, resulting in substantial waste and potential diversion, a prospective cohort study has found.
In an evaluation of 176 narcotic-naive patients who underwent surgery in a over the 14-day postdischarge study period was 30 morphine milligram equivalents (MME) but the median prescription was 150 MME, reported Wen Hui Tan, MD, and her research team at Washington University, St. Louis. The report was published in the Journal of the American College of Surgeons.
Overall, 76.7% of patients reported being satisfied or very satisfied with their postoperative pain management. Some patients (n = 31, 17.6%) reported not filling their prescription or not taking any of their prescribed opioid pain medications at all.
Sixty-nine percent of the surgeries were laparoscopic. A variety of abdominal procedures were represented, including hiatal hernia repair, inguinal hernia repair, and cholecystectomy. The median age was 60 years. Of postoperative pain prescriptions, 67% were for hydrocodone-acetaminophen and most of the remainder were for oxycodone-acetaminophen or oxycodone alone. The median prescription was for the equivalent of 20 5-mg oxycodone pills, while the median consumption in the first 7 postoperative days was 3.7 pills. Only 4.5% of patients received a refill.
The findings are consistent with numerous studies of different types of operations showing that patients often don’t use all of the opioid medications they are prescribed for pain control after surgery.
“Now that opioid pain medications can no longer be refilled with a pharmacy via telephone, overprescription may also be partially driven by a desire to prevent future inconvenience and workload of office staff from patients requesting refills. However, the rising numbers of opioid-related unintentional deaths over the last decade point to the fact that overprescription has serious potential consequences,” the researchers wrote.
They reported having no potential conflicts of interest.
SOURCE: Tan et al. J Am Coll Surg 2018 May 7. doi: 10.1016/j.jamcollsurg.2018.04.032.
Most patients use far less opioids than they are prescribed after hernia and other abdominal surgery, resulting in substantial waste and potential diversion, a prospective cohort study has found.
In an evaluation of 176 narcotic-naive patients who underwent surgery in a over the 14-day postdischarge study period was 30 morphine milligram equivalents (MME) but the median prescription was 150 MME, reported Wen Hui Tan, MD, and her research team at Washington University, St. Louis. The report was published in the Journal of the American College of Surgeons.
Overall, 76.7% of patients reported being satisfied or very satisfied with their postoperative pain management. Some patients (n = 31, 17.6%) reported not filling their prescription or not taking any of their prescribed opioid pain medications at all.
Sixty-nine percent of the surgeries were laparoscopic. A variety of abdominal procedures were represented, including hiatal hernia repair, inguinal hernia repair, and cholecystectomy. The median age was 60 years. Of postoperative pain prescriptions, 67% were for hydrocodone-acetaminophen and most of the remainder were for oxycodone-acetaminophen or oxycodone alone. The median prescription was for the equivalent of 20 5-mg oxycodone pills, while the median consumption in the first 7 postoperative days was 3.7 pills. Only 4.5% of patients received a refill.
The findings are consistent with numerous studies of different types of operations showing that patients often don’t use all of the opioid medications they are prescribed for pain control after surgery.
“Now that opioid pain medications can no longer be refilled with a pharmacy via telephone, overprescription may also be partially driven by a desire to prevent future inconvenience and workload of office staff from patients requesting refills. However, the rising numbers of opioid-related unintentional deaths over the last decade point to the fact that overprescription has serious potential consequences,” the researchers wrote.
They reported having no potential conflicts of interest.
SOURCE: Tan et al. J Am Coll Surg 2018 May 7. doi: 10.1016/j.jamcollsurg.2018.04.032.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS
Key clinical point: For postoperative recovery, a survey showed that far more opioids are prescribed than are consumed.
Major finding: On average, surgical patients went home with opioid prescriptions of 150 MME but took a median of 30 MME.
Study details: Prospective cohort study.
Disclosures: The authors report no potential conflicts of interest.
Source: Tan et al. J Am Coll Surg 2018 May 7. doi: 10.1016/j.jamcollsurg.2018.04.032.
Eleven on a scale of 1 to 10
I literally rode into the sunset recently as I finished my tour of duty as one of the Director examiners for the American Board of Surgery. I was heading out of St. Louis westward toward my home in Kansas. It was a 9-hour drive, which gave me plenty of time to reflect on the 6 years I shared the responsibility of administering the certifying exam known by most surgeons as “the oral exam.”
Over the last dozen years, Directors V. Suzanne Klimberg and Karen J. Brasel, along with former Executive Director Frank Lewis, a team of psychometricians at the Board, and members of the certification committee of the Board, worked tirelessly to create a testing instrument as fair and statistically sound as possible given the inherently qualitative exam. I believe they did a magnificent job. Gone are the legends of yesteryear where candidates were subjected to the whims of whatever crossed the mind of the examiners, including their prejudices about the “right” answer. The oral exam now represents a well-constructed survey of surgical judgment issues that have been thoroughly vetted.
Being an examiner for the orals means you arrive Sunday afternoon before the exams that are given over the next two and a half days. Each examiner undergoes an overview briefing on Sunday afternoon and then studies “the book” for that test’s content usually until late into the night. This book is an impressive document.
We arise around 0530 to attend a breakfast meeting, which includes breaking into our six-person teams and going over each question that will be given that day. At 0800, the first candidates for the first session walk into a room and meet the two surgeons who will make some of the most important decisions affecting that candidate’s career. If you rate the intensity of this moment on a scale of 1 to 10, this is an 11 for both candidates and examiners. No one in the room knows how it will turn out because every session has its own twists and turns. Everyone there wants to see a passing score, but the two examiners know that they must make a decision that is safe for the public and fair for the candidate.
Twelve exams are given per team per day except for the final day which has only six. So, each team examines 30 candidates over 3 days. I’ve opened a door and shaken the moist hand of 438 candidates. I’ve seen every sort of emotion during those sessions. I’ve had moments of great joy and times of profound sadness as candidates respond to the questions. I’ve always tried to be friendly, but just like surgery, it is a serious business and decisions have to be made. That means ignoring one’s hopes and acting on the best facts available at the moment. Most surgeons remember their oral examiners and what they were asked for a lifetime. I know I do.
I could write a book on this experience (I won’t, though). But as I reflect on my time as a Director, what stands out in my mind are the associate examiners with whom I’ve worked. These surgeons are invited to participate and receive no compensation. It’s 3 days out of their lives, and because they don’t give the exam as frequently as the Directors do, the amount of study and effort is greater for them. Each is selected because he or she is considered to be a thoughtful surgeon with high standards. These surgeons do this job because they care about quality in our profession.
Most of the associates I have worked with are far more accomplished than I. I was once paired with a renowned breast surgeon (okay, it was Kelly K. Hunt). My ego was at great risk because I knew how accomplished she was. But like all the other associates, she was gracious and hard working. We rarely work with another Director, but Anne G. Rizzo, who later became a Director, and I did an exam together. She was a dazzling questioner with very high standards. In other words, she was typical of the people I met. My first associate (also later a Director) was Reid Adams. He was great; I was nervous. My last associate was Marc L. Melcher, a transplant surgeon who asked penetrating questions in a calm manner. I wish I could name each of my associates and thank them for making my work so much better, for teaching me things I didn’t know, for deepening my own knowledge, and serving in a hard job with grace. This column can’t be that long, but you all know who you are. Thank you.
At the end of the day, I believe the oral exam to be a great thing for our profession. When you think about the number of patients potentially affected throughout a surgeon’s career, the impact of decisions made on the day of the exam can be enormous. Given that, over a 20-year career, a surgeon may operate on 25,000 patients, a summative check on a surgeon’s judgment and knowledge is important. Each year, the ABS adjudicates on some 1,100 surgeons. A single year’s set of surgeons over the following 20-year period translates into 27.5 million patients. I hope we never stop doing the orals because of cost, time, or convenience. The exam is just too important to our profession to risk forgoing this last, big step before a surgeon is presented to the world as “certified.”
I literally rode into the sunset recently as I finished my tour of duty as one of the Director examiners for the American Board of Surgery. I was heading out of St. Louis westward toward my home in Kansas. It was a 9-hour drive, which gave me plenty of time to reflect on the 6 years I shared the responsibility of administering the certifying exam known by most surgeons as “the oral exam.”
Over the last dozen years, Directors V. Suzanne Klimberg and Karen J. Brasel, along with former Executive Director Frank Lewis, a team of psychometricians at the Board, and members of the certification committee of the Board, worked tirelessly to create a testing instrument as fair and statistically sound as possible given the inherently qualitative exam. I believe they did a magnificent job. Gone are the legends of yesteryear where candidates were subjected to the whims of whatever crossed the mind of the examiners, including their prejudices about the “right” answer. The oral exam now represents a well-constructed survey of surgical judgment issues that have been thoroughly vetted.
Being an examiner for the orals means you arrive Sunday afternoon before the exams that are given over the next two and a half days. Each examiner undergoes an overview briefing on Sunday afternoon and then studies “the book” for that test’s content usually until late into the night. This book is an impressive document.
We arise around 0530 to attend a breakfast meeting, which includes breaking into our six-person teams and going over each question that will be given that day. At 0800, the first candidates for the first session walk into a room and meet the two surgeons who will make some of the most important decisions affecting that candidate’s career. If you rate the intensity of this moment on a scale of 1 to 10, this is an 11 for both candidates and examiners. No one in the room knows how it will turn out because every session has its own twists and turns. Everyone there wants to see a passing score, but the two examiners know that they must make a decision that is safe for the public and fair for the candidate.
Twelve exams are given per team per day except for the final day which has only six. So, each team examines 30 candidates over 3 days. I’ve opened a door and shaken the moist hand of 438 candidates. I’ve seen every sort of emotion during those sessions. I’ve had moments of great joy and times of profound sadness as candidates respond to the questions. I’ve always tried to be friendly, but just like surgery, it is a serious business and decisions have to be made. That means ignoring one’s hopes and acting on the best facts available at the moment. Most surgeons remember their oral examiners and what they were asked for a lifetime. I know I do.
I could write a book on this experience (I won’t, though). But as I reflect on my time as a Director, what stands out in my mind are the associate examiners with whom I’ve worked. These surgeons are invited to participate and receive no compensation. It’s 3 days out of their lives, and because they don’t give the exam as frequently as the Directors do, the amount of study and effort is greater for them. Each is selected because he or she is considered to be a thoughtful surgeon with high standards. These surgeons do this job because they care about quality in our profession.
Most of the associates I have worked with are far more accomplished than I. I was once paired with a renowned breast surgeon (okay, it was Kelly K. Hunt). My ego was at great risk because I knew how accomplished she was. But like all the other associates, she was gracious and hard working. We rarely work with another Director, but Anne G. Rizzo, who later became a Director, and I did an exam together. She was a dazzling questioner with very high standards. In other words, she was typical of the people I met. My first associate (also later a Director) was Reid Adams. He was great; I was nervous. My last associate was Marc L. Melcher, a transplant surgeon who asked penetrating questions in a calm manner. I wish I could name each of my associates and thank them for making my work so much better, for teaching me things I didn’t know, for deepening my own knowledge, and serving in a hard job with grace. This column can’t be that long, but you all know who you are. Thank you.
At the end of the day, I believe the oral exam to be a great thing for our profession. When you think about the number of patients potentially affected throughout a surgeon’s career, the impact of decisions made on the day of the exam can be enormous. Given that, over a 20-year career, a surgeon may operate on 25,000 patients, a summative check on a surgeon’s judgment and knowledge is important. Each year, the ABS adjudicates on some 1,100 surgeons. A single year’s set of surgeons over the following 20-year period translates into 27.5 million patients. I hope we never stop doing the orals because of cost, time, or convenience. The exam is just too important to our profession to risk forgoing this last, big step before a surgeon is presented to the world as “certified.”
I literally rode into the sunset recently as I finished my tour of duty as one of the Director examiners for the American Board of Surgery. I was heading out of St. Louis westward toward my home in Kansas. It was a 9-hour drive, which gave me plenty of time to reflect on the 6 years I shared the responsibility of administering the certifying exam known by most surgeons as “the oral exam.”
Over the last dozen years, Directors V. Suzanne Klimberg and Karen J. Brasel, along with former Executive Director Frank Lewis, a team of psychometricians at the Board, and members of the certification committee of the Board, worked tirelessly to create a testing instrument as fair and statistically sound as possible given the inherently qualitative exam. I believe they did a magnificent job. Gone are the legends of yesteryear where candidates were subjected to the whims of whatever crossed the mind of the examiners, including their prejudices about the “right” answer. The oral exam now represents a well-constructed survey of surgical judgment issues that have been thoroughly vetted.
Being an examiner for the orals means you arrive Sunday afternoon before the exams that are given over the next two and a half days. Each examiner undergoes an overview briefing on Sunday afternoon and then studies “the book” for that test’s content usually until late into the night. This book is an impressive document.
We arise around 0530 to attend a breakfast meeting, which includes breaking into our six-person teams and going over each question that will be given that day. At 0800, the first candidates for the first session walk into a room and meet the two surgeons who will make some of the most important decisions affecting that candidate’s career. If you rate the intensity of this moment on a scale of 1 to 10, this is an 11 for both candidates and examiners. No one in the room knows how it will turn out because every session has its own twists and turns. Everyone there wants to see a passing score, but the two examiners know that they must make a decision that is safe for the public and fair for the candidate.
Twelve exams are given per team per day except for the final day which has only six. So, each team examines 30 candidates over 3 days. I’ve opened a door and shaken the moist hand of 438 candidates. I’ve seen every sort of emotion during those sessions. I’ve had moments of great joy and times of profound sadness as candidates respond to the questions. I’ve always tried to be friendly, but just like surgery, it is a serious business and decisions have to be made. That means ignoring one’s hopes and acting on the best facts available at the moment. Most surgeons remember their oral examiners and what they were asked for a lifetime. I know I do.
I could write a book on this experience (I won’t, though). But as I reflect on my time as a Director, what stands out in my mind are the associate examiners with whom I’ve worked. These surgeons are invited to participate and receive no compensation. It’s 3 days out of their lives, and because they don’t give the exam as frequently as the Directors do, the amount of study and effort is greater for them. Each is selected because he or she is considered to be a thoughtful surgeon with high standards. These surgeons do this job because they care about quality in our profession.
Most of the associates I have worked with are far more accomplished than I. I was once paired with a renowned breast surgeon (okay, it was Kelly K. Hunt). My ego was at great risk because I knew how accomplished she was. But like all the other associates, she was gracious and hard working. We rarely work with another Director, but Anne G. Rizzo, who later became a Director, and I did an exam together. She was a dazzling questioner with very high standards. In other words, she was typical of the people I met. My first associate (also later a Director) was Reid Adams. He was great; I was nervous. My last associate was Marc L. Melcher, a transplant surgeon who asked penetrating questions in a calm manner. I wish I could name each of my associates and thank them for making my work so much better, for teaching me things I didn’t know, for deepening my own knowledge, and serving in a hard job with grace. This column can’t be that long, but you all know who you are. Thank you.
At the end of the day, I believe the oral exam to be a great thing for our profession. When you think about the number of patients potentially affected throughout a surgeon’s career, the impact of decisions made on the day of the exam can be enormous. Given that, over a 20-year career, a surgeon may operate on 25,000 patients, a summative check on a surgeon’s judgment and knowledge is important. Each year, the ABS adjudicates on some 1,100 surgeons. A single year’s set of surgeons over the following 20-year period translates into 27.5 million patients. I hope we never stop doing the orals because of cost, time, or convenience. The exam is just too important to our profession to risk forgoing this last, big step before a surgeon is presented to the world as “certified.”
Valbenazine Provides Long-Term Benefits for Tardive Dyskinesia
LOS ANGELES—Once-daily treatment with valbenazine for 48 weeks provides substantial improvements on clinician- and patient-reported outcomes in adults with tardive dyskinesia, according to data described at the 70th Annual Meeting of the American Academy of Neurology. The results are consistent with those of previous trials, said the researchers. Valbenazine is well tolerated and does not raise significant safety concerns.
Valbenazine was approved as a treatment for tardive dyskinesia on the basis of several short-term placebo-controlled trials, a blinded extension study, and the long-term KINECT 4 study. Stewart Factor, DO, Professor of Neurology at Emory University School of Medicine in Atlanta, and colleagues conducted a study to evaluate the long-term effects of once-daily valbenazine on tardive dyskinesia.
Eligible participants were adults with de novo tardive dyskinesia and those who had participated in prior trials of valbenazine. All participants received 48 weeks of open-label treatment with valbenazine. The initial dose was 40 mg. If an investigator judged that a patient had inadequate clinical response at week four, the dose was increased to 80 mg, based on tolerability. For patients who could not tolerate the 80-mg dose, the dose was decreased to 40 mg.
Dr. Factor and colleagues used the change from baseline in the Abnormal Involuntary Movement Scale (AIMS) total score to assess changes in tardive dyskinesia. Other efficacy assessments included the Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) scales. The investigators applied standard safety methods, including treatment-emergent adverse event reporting.
The safety population included 163 participants. Of this group, 107 participants received and tolerated the 80-mg dose, 45 did not require escalation from the 40-mg dose, and 11 were escalated to 80-mg dose, but later required reduction to the 40-mg dose. The mean change from baseline to week 48 in AIMS total score indicated improvements in tardive dyskinesia in all dose groups. The 80-mg group had a decrease of 11.0 points, the 40-mg group had a decrease of 10.2 points, and the group whose dose was decreased from 80 mg to 40 mg had a decrease of 7.2 points.
At week 48, more than 75% of participants in each study arm had a PGIC score of 2 or lower (ie, much improved or very much improved). This outcome was achieved in 89.2% of the 80-mg group, 90.0% of the 40-mg group, and 77.8% of the group whose dose was decreased from 80 mg to 40 mg. Mean CGI-TD scores at week 48 were 1.6 for the 80-mg group, 1.7 for the 40-mg group, and 2.3 for the group whose dose was reduced from 80 mg to 40 mg. These scores indicated clinically meaningful long-term improvement for all dose groups.
Less than 15% of all participants had a serious treatment-emergent adverse event (12.9%) or treatment-emergent adverse event leading to discontinuation (14.7%).
The study was funded by Neurocrine Biosciences, the manufacturer of valbenazine.
LOS ANGELES—Once-daily treatment with valbenazine for 48 weeks provides substantial improvements on clinician- and patient-reported outcomes in adults with tardive dyskinesia, according to data described at the 70th Annual Meeting of the American Academy of Neurology. The results are consistent with those of previous trials, said the researchers. Valbenazine is well tolerated and does not raise significant safety concerns.
Valbenazine was approved as a treatment for tardive dyskinesia on the basis of several short-term placebo-controlled trials, a blinded extension study, and the long-term KINECT 4 study. Stewart Factor, DO, Professor of Neurology at Emory University School of Medicine in Atlanta, and colleagues conducted a study to evaluate the long-term effects of once-daily valbenazine on tardive dyskinesia.
Eligible participants were adults with de novo tardive dyskinesia and those who had participated in prior trials of valbenazine. All participants received 48 weeks of open-label treatment with valbenazine. The initial dose was 40 mg. If an investigator judged that a patient had inadequate clinical response at week four, the dose was increased to 80 mg, based on tolerability. For patients who could not tolerate the 80-mg dose, the dose was decreased to 40 mg.
Dr. Factor and colleagues used the change from baseline in the Abnormal Involuntary Movement Scale (AIMS) total score to assess changes in tardive dyskinesia. Other efficacy assessments included the Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) scales. The investigators applied standard safety methods, including treatment-emergent adverse event reporting.
The safety population included 163 participants. Of this group, 107 participants received and tolerated the 80-mg dose, 45 did not require escalation from the 40-mg dose, and 11 were escalated to 80-mg dose, but later required reduction to the 40-mg dose. The mean change from baseline to week 48 in AIMS total score indicated improvements in tardive dyskinesia in all dose groups. The 80-mg group had a decrease of 11.0 points, the 40-mg group had a decrease of 10.2 points, and the group whose dose was decreased from 80 mg to 40 mg had a decrease of 7.2 points.
At week 48, more than 75% of participants in each study arm had a PGIC score of 2 or lower (ie, much improved or very much improved). This outcome was achieved in 89.2% of the 80-mg group, 90.0% of the 40-mg group, and 77.8% of the group whose dose was decreased from 80 mg to 40 mg. Mean CGI-TD scores at week 48 were 1.6 for the 80-mg group, 1.7 for the 40-mg group, and 2.3 for the group whose dose was reduced from 80 mg to 40 mg. These scores indicated clinically meaningful long-term improvement for all dose groups.
Less than 15% of all participants had a serious treatment-emergent adverse event (12.9%) or treatment-emergent adverse event leading to discontinuation (14.7%).
The study was funded by Neurocrine Biosciences, the manufacturer of valbenazine.
LOS ANGELES—Once-daily treatment with valbenazine for 48 weeks provides substantial improvements on clinician- and patient-reported outcomes in adults with tardive dyskinesia, according to data described at the 70th Annual Meeting of the American Academy of Neurology. The results are consistent with those of previous trials, said the researchers. Valbenazine is well tolerated and does not raise significant safety concerns.
Valbenazine was approved as a treatment for tardive dyskinesia on the basis of several short-term placebo-controlled trials, a blinded extension study, and the long-term KINECT 4 study. Stewart Factor, DO, Professor of Neurology at Emory University School of Medicine in Atlanta, and colleagues conducted a study to evaluate the long-term effects of once-daily valbenazine on tardive dyskinesia.
Eligible participants were adults with de novo tardive dyskinesia and those who had participated in prior trials of valbenazine. All participants received 48 weeks of open-label treatment with valbenazine. The initial dose was 40 mg. If an investigator judged that a patient had inadequate clinical response at week four, the dose was increased to 80 mg, based on tolerability. For patients who could not tolerate the 80-mg dose, the dose was decreased to 40 mg.
Dr. Factor and colleagues used the change from baseline in the Abnormal Involuntary Movement Scale (AIMS) total score to assess changes in tardive dyskinesia. Other efficacy assessments included the Patient Global Impression of Change (PGIC) and Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD) scales. The investigators applied standard safety methods, including treatment-emergent adverse event reporting.
The safety population included 163 participants. Of this group, 107 participants received and tolerated the 80-mg dose, 45 did not require escalation from the 40-mg dose, and 11 were escalated to 80-mg dose, but later required reduction to the 40-mg dose. The mean change from baseline to week 48 in AIMS total score indicated improvements in tardive dyskinesia in all dose groups. The 80-mg group had a decrease of 11.0 points, the 40-mg group had a decrease of 10.2 points, and the group whose dose was decreased from 80 mg to 40 mg had a decrease of 7.2 points.
At week 48, more than 75% of participants in each study arm had a PGIC score of 2 or lower (ie, much improved or very much improved). This outcome was achieved in 89.2% of the 80-mg group, 90.0% of the 40-mg group, and 77.8% of the group whose dose was decreased from 80 mg to 40 mg. Mean CGI-TD scores at week 48 were 1.6 for the 80-mg group, 1.7 for the 40-mg group, and 2.3 for the group whose dose was reduced from 80 mg to 40 mg. These scores indicated clinically meaningful long-term improvement for all dose groups.
Less than 15% of all participants had a serious treatment-emergent adverse event (12.9%) or treatment-emergent adverse event leading to discontinuation (14.7%).
The study was funded by Neurocrine Biosciences, the manufacturer of valbenazine.
Long-Term Perampanel Treatment Is Safe and Effective for Adolescents
LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.
Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.
Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.
The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.
The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.
For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.
The study was supported by Eisai.
LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.
Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.
Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.
The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.
The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.
For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.
The study was supported by Eisai.
LOS ANGELES—Treatment for as long as four years with adjunctive perampanel is safe and effective for adolescents with secondarily generalized seizures or primary generalized tonic-clonic seizures, according to a post hoc study presented at the 70th Annual Meeting of the American Academy of Neurology. “These post hoc results are encouraging, given the refractory nature of these seizure types,” said the investigators.
Perampanel has regulatory approval for the treatment of partial seizures with or without secondarily generalized seizures, and for the adjunctive treatment of primary generalized tonic-clonic seizures in patients age 12 and younger with epilepsy. Phase II and III randomized, double-blind, placebo-controlled trials indicated that adjunctive perampanel (at doses of 12 mg/day or less) was effective and tolerable in patients with these types of seizures in idiopathic generalized epilepsy. The participants who completed these studies were eligible to enter one of four open-label extension studies.
Jesus Eric Piña-Garza, MD, a pediatric neurologist at the Children’s Hospital at TriStar Centennial in Nashville, and colleagues used data from these open-label extension studies to assess the long-term efficacy and safety of adjunctive perampanel in patients from ages 12 to 17 with secondarily generalized seizures or primary generalized tonic-clonic seizures.
The extension studies incorporated a blinded conversion period that lasted for six to 16 weeks, during which perampanel dose was optimized (at 12 mg/day or less), and a maintenance phase that lasted for 27 to 256 weeks. Total drug exposure was as long as five years. All patients received perampanel during these studies. Efficacy and safety assessments, which were performed for as long as four years, included median percent change in seizure frequency per 28 days and 50% and 75% responder and seizure-freedom rates. Investigators also monitored treatment-emergent adverse events.
The investigators included 129 adolescent patients in the safety analysis set, including 109 with secondarily generalized seizures and 19 with primary generalized tonic-clonic seizures. During the first year, median percent reductions in seizure frequency per 28 days were 62.8% for patients with secondarily generalized seizures and 84.0% for patients with primary generalized tonic-clonic seizures. During year four, median percent reductions in seizure frequency per 28 days were 73.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures. The 50% responder rates were 56.9% for patients with secondarily generalized seizures and 63.2% for patients with primary generalized tonic-clonic seizures in year one, and 65.2% for patients with secondarily generalized seizures and 100.0% for patients with primary generalized tonic-clonic seizures in year four.
For each seizure type, the incidence of treatment-emergent adverse events was highest during the first year of perampanel exposure. The most common treatment-emergent adverse events were dizziness, somnolence, and nasopharyngitis.
The study was supported by Eisai.
Multisensory Impairment Is Associated With Risk of Dementia
LOS ANGELES—Among older adults, the presence of a greater number of sensory impairments is associated with an increased risk of dementia, according to research presented at the 70th Annual Meeting of the American Academy of Neurology.
Sensory impairments are common among older adults and are associated with dementia, but no study has examined multisensory impairment and risk of dementia by incorporating measures of hearing, vision, smell, and touch, said Willa D. Brenowitz, PhD, MPH, a researcher in the Department of Epidemiology and Biostatistics at the University of California, San Francisco, and colleagues.
To evaluate whether the presence of multiple sensory impairments is associated with a greater risk of dementia, compared with a single or no sensory impairment, Dr. Brenowitz and colleagues studied 1,843 participants from the Health, Aging, and Body Composition Study. Participants were ages 70 to 79 and did not have dementia at baseline.
Investigators used sensory assessments that were conducted during the study years 3–5 to determine whether participants had visual impairment (ie, visual acuity ≤ 20/40 or log contrast sensitivity < 1.55), moderate to severe hearing loss (> 40 decibels hearing level based on pure tone average at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz), poor smell (lowest tertile of 12-item Cross Cultural Smell Identification Test), or impaired touch (peripheral nerve insensitivity based on a 10-g monofilament test or vibration detection threshold).
Investigators followed participants for up to 10 years. Incident dementia was based on hospitalization records, dementia medications, or a decline in Modified Mini-Mental State Exam of 1.5 standard deviations or greater. The researchers evaluated the association between number of sensory impairments and risk of dementia using Cox proportional hazard models adjusted for demographics and health conditions.
Sensory impairments were common, the researchers said. In all, 28% had visual impairments, 35% had hearing loss, 22% had poor smell, 12% had peripheral nerve insensitivity, and 25% had multiple impairments. An increasing number of impairments was associated with risk of dementia in a graded fashion. Compared with no sensory impairment, having one sensory impairment was associated with a 50% greater risk of dementia, two impairments was associated with a twofold greater risk of dementia, and three or four impairments was associated with a 2.8-fold greater risk of dementia.
“It is possible that sensory impairment, especially multiple [impairments], could limit an older adult’s engagement in protective lifestyle factors such as cognitive, physical, and social activity, thereby increasing dementia risk,” Dr. Brenowitz and colleagues said.
Clinical assessment of sensory function may help identify patients at high risk of dementia. Further studies are needed to determine whether multisensory impairment is a risk factor for dementia or an indicator of neurodegeneration, the researchers said.
—Jake Remaly
LOS ANGELES—Among older adults, the presence of a greater number of sensory impairments is associated with an increased risk of dementia, according to research presented at the 70th Annual Meeting of the American Academy of Neurology.
Sensory impairments are common among older adults and are associated with dementia, but no study has examined multisensory impairment and risk of dementia by incorporating measures of hearing, vision, smell, and touch, said Willa D. Brenowitz, PhD, MPH, a researcher in the Department of Epidemiology and Biostatistics at the University of California, San Francisco, and colleagues.
To evaluate whether the presence of multiple sensory impairments is associated with a greater risk of dementia, compared with a single or no sensory impairment, Dr. Brenowitz and colleagues studied 1,843 participants from the Health, Aging, and Body Composition Study. Participants were ages 70 to 79 and did not have dementia at baseline.
Investigators used sensory assessments that were conducted during the study years 3–5 to determine whether participants had visual impairment (ie, visual acuity ≤ 20/40 or log contrast sensitivity < 1.55), moderate to severe hearing loss (> 40 decibels hearing level based on pure tone average at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz), poor smell (lowest tertile of 12-item Cross Cultural Smell Identification Test), or impaired touch (peripheral nerve insensitivity based on a 10-g monofilament test or vibration detection threshold).
Investigators followed participants for up to 10 years. Incident dementia was based on hospitalization records, dementia medications, or a decline in Modified Mini-Mental State Exam of 1.5 standard deviations or greater. The researchers evaluated the association between number of sensory impairments and risk of dementia using Cox proportional hazard models adjusted for demographics and health conditions.
Sensory impairments were common, the researchers said. In all, 28% had visual impairments, 35% had hearing loss, 22% had poor smell, 12% had peripheral nerve insensitivity, and 25% had multiple impairments. An increasing number of impairments was associated with risk of dementia in a graded fashion. Compared with no sensory impairment, having one sensory impairment was associated with a 50% greater risk of dementia, two impairments was associated with a twofold greater risk of dementia, and three or four impairments was associated with a 2.8-fold greater risk of dementia.
“It is possible that sensory impairment, especially multiple [impairments], could limit an older adult’s engagement in protective lifestyle factors such as cognitive, physical, and social activity, thereby increasing dementia risk,” Dr. Brenowitz and colleagues said.
Clinical assessment of sensory function may help identify patients at high risk of dementia. Further studies are needed to determine whether multisensory impairment is a risk factor for dementia or an indicator of neurodegeneration, the researchers said.
—Jake Remaly
LOS ANGELES—Among older adults, the presence of a greater number of sensory impairments is associated with an increased risk of dementia, according to research presented at the 70th Annual Meeting of the American Academy of Neurology.
Sensory impairments are common among older adults and are associated with dementia, but no study has examined multisensory impairment and risk of dementia by incorporating measures of hearing, vision, smell, and touch, said Willa D. Brenowitz, PhD, MPH, a researcher in the Department of Epidemiology and Biostatistics at the University of California, San Francisco, and colleagues.
To evaluate whether the presence of multiple sensory impairments is associated with a greater risk of dementia, compared with a single or no sensory impairment, Dr. Brenowitz and colleagues studied 1,843 participants from the Health, Aging, and Body Composition Study. Participants were ages 70 to 79 and did not have dementia at baseline.
Investigators used sensory assessments that were conducted during the study years 3–5 to determine whether participants had visual impairment (ie, visual acuity ≤ 20/40 or log contrast sensitivity < 1.55), moderate to severe hearing loss (> 40 decibels hearing level based on pure tone average at 500 Hz, 1,000 Hz, 2,000 Hz, and 4,000 Hz), poor smell (lowest tertile of 12-item Cross Cultural Smell Identification Test), or impaired touch (peripheral nerve insensitivity based on a 10-g monofilament test or vibration detection threshold).
Investigators followed participants for up to 10 years. Incident dementia was based on hospitalization records, dementia medications, or a decline in Modified Mini-Mental State Exam of 1.5 standard deviations or greater. The researchers evaluated the association between number of sensory impairments and risk of dementia using Cox proportional hazard models adjusted for demographics and health conditions.
Sensory impairments were common, the researchers said. In all, 28% had visual impairments, 35% had hearing loss, 22% had poor smell, 12% had peripheral nerve insensitivity, and 25% had multiple impairments. An increasing number of impairments was associated with risk of dementia in a graded fashion. Compared with no sensory impairment, having one sensory impairment was associated with a 50% greater risk of dementia, two impairments was associated with a twofold greater risk of dementia, and three or four impairments was associated with a 2.8-fold greater risk of dementia.
“It is possible that sensory impairment, especially multiple [impairments], could limit an older adult’s engagement in protective lifestyle factors such as cognitive, physical, and social activity, thereby increasing dementia risk,” Dr. Brenowitz and colleagues said.
Clinical assessment of sensory function may help identify patients at high risk of dementia. Further studies are needed to determine whether multisensory impairment is a risk factor for dementia or an indicator of neurodegeneration, the researchers said.
—Jake Remaly