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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
Early PCI now favored in stable CAD
PARIS – A strong tide has turned in favor of early percutaneous coronary intervention in patients with stable coronary artery disease, with the proviso that they must display objective evidence of hemodynamically significant stenosis as demonstrated by measurement of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR).
Indeed, the consistent results of multiple studies presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions prompted the meeting organizers to issue a formal summary statement.
“PCI results in less angina, better quality of life, less urgent revascularizations, and less spontaneous MIs compared to medical treatment alone. The longer the observation period is, the more benefit is shown for PCI,” declared Michael Haude, MD, president of the European Association of Percutaneous Cardiovascular Interventions and a cardiologist at Heinrich Heine University in Düsseldorf, Germany.
“” on the basis of the latest studies featuring a contemporary approach, said Dr. Haude, noting that most prior studies of PCI versus medical therapy alone did not use latest-generation drug-eluting stent technology, featuring thin struts, improved antirestenosis drugs, and better drug-release technology and kinetics.
Among the persuasively positive studies presented at EuroPCR 2018 were the 5-year outcomes of FFR-guided PCI versus medical therapy alone in the FAME 2 trial, a secondary analysis of the controversial ORBITA trial, which placed early PCI for stable CAD in a more favorable light than initially reported, and an analysis from the comprehensive national Swedish Coronary Angiography and Angioplasty Registry (SCAAR).
These and several other studies presented at the conference conveyed a consistent message that early PCI in patients with stable CAD and physiologically significant coronary lesions results in improved clinical outcomes and symptomatic relief compared with medical management alone. Conversely, in patients without objective evidence of potentially reversible ischemia based on FFR or iFR, there is no reason to expect benefit from revascularization.
FAME 2
Panagiotis Xaplanteris, MD, PhD, of the Cardiovascular Center at Aalst, Belgium, presented the final 5-year follow-up of FAME 2 (the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2) trial, in which 888 patients with stable CAD and at least one hemodynamically significant coronary stenosis as defined by an FFR value of 0.80 or less in a major artery were randomized to FFR-guided PCI plus guideline-directed medical therapy or to medical therapy alone.
The long-term favorable impact of the early interventional strategy was striking: At 5 years, the rate of the primary composite endpoint of death, MI, or urgent revascularization was 13.9% in the early PCI group, roughly half of the 27% rate in the medically managed group. And this intention-to-treat analysis understates the true benefit of early PCI, since by the 5-year mark fully 51% of patients in the medically managed arm had crossed over to PCI.
The difference in the composite endpoint was driven largely by the early PCI group’s lesser need for urgent revascularization, defined as revascularization performed during any unplanned hospital admission for symptoms prompting revascularization. Most of these urgent revascularizations were prompted by in-hospital positive cardiac biomarkers, ECG changes, or unstable angina.
An important finding that was not apparent during shorter-term follow-up is that, by the 5-year mark, the early PCI strategy conferred a significant reduction in the risk of acute MI: 8.1% versus 12%. This difference was mainly due to the early PCI group’s lower rate of nonprocedurally related spontaneous MI: 6.5% compared with 10.2% in the control group, for a 38% relative risk reduction.
Discussant Philip Urban, MD, director of interventional cardiology at Hospital de la Tour in Geneva, said the take-home message from FAME 2 for him was simple: “If it ain’t broke, don’t fix it; but if it is, don’t procrastinate.”
Martin B. Leon, MD, observed that, up until now, when he has discussed with patients who have stable CAD the possibility of undergoing PCI, he has described the potential benefits as being reduced ischemia and improved symptoms with no significant impact on the hard endpoints of acute MI or death. FAME 2 has changed all that.
“What I really enjoyed about this presentation is that you dissected the improvement and demonstrated clearly that spontaneous MIs are in fact reduced with PCI in patients with stable CAD, which is a hard endpoint. And I would even argue that yours is a minimalistic analysis in the sense that many of the urgent revascularization patients likely would have ended up being nontransmural MIs as well. So I think this gives credence to the understanding that PCI not only affects ischemia but also affects the hard endpoint of spontaneous MI. And you need a large study like this with a 5-year endpoint to clarify those issues,” noted Dr. Leon, professor of medicine at Columbia University in New York.
ORBITA revisited
ORBITA was the first-ever randomized blinded trial of real versus sham PCI in patients with stable CAD. When Rasha Al-Lamee, MD, presented the primary results at the TCT 2017 conference in Denver, reporting that PCI failed to show a significant improvement in exercise time compared with placebo PCI, reaction was swift and furious. Interventionalists criticized the study’s choice of treadmill exercise time as an inappropriately squishy primary endpoint. Noninterventionalists saw ORBITA as confirming their view that many interventional cardiologists are catheter cowboys.
However, with additional time for further data analysis, Dr. Al-Lamee reported at EuroPCR 2018 that, in fact, the degree of ischemia seen on baseline iFR and FFR entirely predicted the extent of objective improvement in ischemia on dobutamine stress echocardiography in response to PCI. The 25% of participants whose iFR and FFR were greater than the generally accepted thresholds for intervention did not derive any significant placebo-subtracted benefit from PCI. In contrast, the lower the baseline FFR and iFR values – meaning the greater the impairment of blood flow across a stenotic lesion – the greater the reduction in ischemia in response to true PCI.
Of note, at the end of the 6-week blinded study period, 85% of patients in the control group opted for PCI.
“This is the trial everyone is talking about. Even on Twitter, it’s really dominating,” observed discussant Davide Capodanno, MD, PhD, of the University of Catania, Italy. “And this new freedom from angina endpoint, this is a win for PCI.”
Asked what she would do differently if she could do ORBITA over again, Dr. Al-Lamee didn’t hesitate: “If I were to do it again, I absolutely agree that exercise time would not be the primary endpoint I would choose.”
SCAAR
Elmir Omerovic, MD, PhD, presented an update from the long-running observational prospective Swedish national registry. The analysis included 3,460 patients who underwent PCI for stable angina with FFR and/or iFR guidance and 21,221 others whose PCI was performed based solely on coronary angiography.
At the beginning of the 10-year study period, FFR/iFR was utilized in 5%-6% of PCIs for stable CAD; today that rate has climbed to 40%, according to the cardiologist.
He reported no financial conflicts of interest regarding his study.
Simultaneously with Dr. Xaplanteris’ presentation of the final 5-year outcomes of FAME 2, the results were published online (N Engl J Med. 2018 May 22. doi: 10.1056/NEJMoa1803538). He reported having no financial conflicts of interest.
Similarly, Dr. Al-Lamee’s updated analysis of ORBITA was simultaneously published (Circulation. 2018 May 22. doi: 10.11161/CIRCULATIONAHA.118.033801). She, too, reported having no financial conflicts regarding this investigator-initiated study.
Dr. Haude expressed confidence that these studies will result in significant changes in the next iteration of the European Society of Cardiology guidelines on chronic coronary syndrome, likely to be issued in 2019 or 2020.
PARIS – A strong tide has turned in favor of early percutaneous coronary intervention in patients with stable coronary artery disease, with the proviso that they must display objective evidence of hemodynamically significant stenosis as demonstrated by measurement of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR).
Indeed, the consistent results of multiple studies presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions prompted the meeting organizers to issue a formal summary statement.
“PCI results in less angina, better quality of life, less urgent revascularizations, and less spontaneous MIs compared to medical treatment alone. The longer the observation period is, the more benefit is shown for PCI,” declared Michael Haude, MD, president of the European Association of Percutaneous Cardiovascular Interventions and a cardiologist at Heinrich Heine University in Düsseldorf, Germany.
“” on the basis of the latest studies featuring a contemporary approach, said Dr. Haude, noting that most prior studies of PCI versus medical therapy alone did not use latest-generation drug-eluting stent technology, featuring thin struts, improved antirestenosis drugs, and better drug-release technology and kinetics.
Among the persuasively positive studies presented at EuroPCR 2018 were the 5-year outcomes of FFR-guided PCI versus medical therapy alone in the FAME 2 trial, a secondary analysis of the controversial ORBITA trial, which placed early PCI for stable CAD in a more favorable light than initially reported, and an analysis from the comprehensive national Swedish Coronary Angiography and Angioplasty Registry (SCAAR).
These and several other studies presented at the conference conveyed a consistent message that early PCI in patients with stable CAD and physiologically significant coronary lesions results in improved clinical outcomes and symptomatic relief compared with medical management alone. Conversely, in patients without objective evidence of potentially reversible ischemia based on FFR or iFR, there is no reason to expect benefit from revascularization.
FAME 2
Panagiotis Xaplanteris, MD, PhD, of the Cardiovascular Center at Aalst, Belgium, presented the final 5-year follow-up of FAME 2 (the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2) trial, in which 888 patients with stable CAD and at least one hemodynamically significant coronary stenosis as defined by an FFR value of 0.80 or less in a major artery were randomized to FFR-guided PCI plus guideline-directed medical therapy or to medical therapy alone.
The long-term favorable impact of the early interventional strategy was striking: At 5 years, the rate of the primary composite endpoint of death, MI, or urgent revascularization was 13.9% in the early PCI group, roughly half of the 27% rate in the medically managed group. And this intention-to-treat analysis understates the true benefit of early PCI, since by the 5-year mark fully 51% of patients in the medically managed arm had crossed over to PCI.
The difference in the composite endpoint was driven largely by the early PCI group’s lesser need for urgent revascularization, defined as revascularization performed during any unplanned hospital admission for symptoms prompting revascularization. Most of these urgent revascularizations were prompted by in-hospital positive cardiac biomarkers, ECG changes, or unstable angina.
An important finding that was not apparent during shorter-term follow-up is that, by the 5-year mark, the early PCI strategy conferred a significant reduction in the risk of acute MI: 8.1% versus 12%. This difference was mainly due to the early PCI group’s lower rate of nonprocedurally related spontaneous MI: 6.5% compared with 10.2% in the control group, for a 38% relative risk reduction.
Discussant Philip Urban, MD, director of interventional cardiology at Hospital de la Tour in Geneva, said the take-home message from FAME 2 for him was simple: “If it ain’t broke, don’t fix it; but if it is, don’t procrastinate.”
Martin B. Leon, MD, observed that, up until now, when he has discussed with patients who have stable CAD the possibility of undergoing PCI, he has described the potential benefits as being reduced ischemia and improved symptoms with no significant impact on the hard endpoints of acute MI or death. FAME 2 has changed all that.
“What I really enjoyed about this presentation is that you dissected the improvement and demonstrated clearly that spontaneous MIs are in fact reduced with PCI in patients with stable CAD, which is a hard endpoint. And I would even argue that yours is a minimalistic analysis in the sense that many of the urgent revascularization patients likely would have ended up being nontransmural MIs as well. So I think this gives credence to the understanding that PCI not only affects ischemia but also affects the hard endpoint of spontaneous MI. And you need a large study like this with a 5-year endpoint to clarify those issues,” noted Dr. Leon, professor of medicine at Columbia University in New York.
ORBITA revisited
ORBITA was the first-ever randomized blinded trial of real versus sham PCI in patients with stable CAD. When Rasha Al-Lamee, MD, presented the primary results at the TCT 2017 conference in Denver, reporting that PCI failed to show a significant improvement in exercise time compared with placebo PCI, reaction was swift and furious. Interventionalists criticized the study’s choice of treadmill exercise time as an inappropriately squishy primary endpoint. Noninterventionalists saw ORBITA as confirming their view that many interventional cardiologists are catheter cowboys.
However, with additional time for further data analysis, Dr. Al-Lamee reported at EuroPCR 2018 that, in fact, the degree of ischemia seen on baseline iFR and FFR entirely predicted the extent of objective improvement in ischemia on dobutamine stress echocardiography in response to PCI. The 25% of participants whose iFR and FFR were greater than the generally accepted thresholds for intervention did not derive any significant placebo-subtracted benefit from PCI. In contrast, the lower the baseline FFR and iFR values – meaning the greater the impairment of blood flow across a stenotic lesion – the greater the reduction in ischemia in response to true PCI.
Of note, at the end of the 6-week blinded study period, 85% of patients in the control group opted for PCI.
“This is the trial everyone is talking about. Even on Twitter, it’s really dominating,” observed discussant Davide Capodanno, MD, PhD, of the University of Catania, Italy. “And this new freedom from angina endpoint, this is a win for PCI.”
Asked what she would do differently if she could do ORBITA over again, Dr. Al-Lamee didn’t hesitate: “If I were to do it again, I absolutely agree that exercise time would not be the primary endpoint I would choose.”
SCAAR
Elmir Omerovic, MD, PhD, presented an update from the long-running observational prospective Swedish national registry. The analysis included 3,460 patients who underwent PCI for stable angina with FFR and/or iFR guidance and 21,221 others whose PCI was performed based solely on coronary angiography.
At the beginning of the 10-year study period, FFR/iFR was utilized in 5%-6% of PCIs for stable CAD; today that rate has climbed to 40%, according to the cardiologist.
He reported no financial conflicts of interest regarding his study.
Simultaneously with Dr. Xaplanteris’ presentation of the final 5-year outcomes of FAME 2, the results were published online (N Engl J Med. 2018 May 22. doi: 10.1056/NEJMoa1803538). He reported having no financial conflicts of interest.
Similarly, Dr. Al-Lamee’s updated analysis of ORBITA was simultaneously published (Circulation. 2018 May 22. doi: 10.11161/CIRCULATIONAHA.118.033801). She, too, reported having no financial conflicts regarding this investigator-initiated study.
Dr. Haude expressed confidence that these studies will result in significant changes in the next iteration of the European Society of Cardiology guidelines on chronic coronary syndrome, likely to be issued in 2019 or 2020.
PARIS – A strong tide has turned in favor of early percutaneous coronary intervention in patients with stable coronary artery disease, with the proviso that they must display objective evidence of hemodynamically significant stenosis as demonstrated by measurement of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR).
Indeed, the consistent results of multiple studies presented at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions prompted the meeting organizers to issue a formal summary statement.
“PCI results in less angina, better quality of life, less urgent revascularizations, and less spontaneous MIs compared to medical treatment alone. The longer the observation period is, the more benefit is shown for PCI,” declared Michael Haude, MD, president of the European Association of Percutaneous Cardiovascular Interventions and a cardiologist at Heinrich Heine University in Düsseldorf, Germany.
“” on the basis of the latest studies featuring a contemporary approach, said Dr. Haude, noting that most prior studies of PCI versus medical therapy alone did not use latest-generation drug-eluting stent technology, featuring thin struts, improved antirestenosis drugs, and better drug-release technology and kinetics.
Among the persuasively positive studies presented at EuroPCR 2018 were the 5-year outcomes of FFR-guided PCI versus medical therapy alone in the FAME 2 trial, a secondary analysis of the controversial ORBITA trial, which placed early PCI for stable CAD in a more favorable light than initially reported, and an analysis from the comprehensive national Swedish Coronary Angiography and Angioplasty Registry (SCAAR).
These and several other studies presented at the conference conveyed a consistent message that early PCI in patients with stable CAD and physiologically significant coronary lesions results in improved clinical outcomes and symptomatic relief compared with medical management alone. Conversely, in patients without objective evidence of potentially reversible ischemia based on FFR or iFR, there is no reason to expect benefit from revascularization.
FAME 2
Panagiotis Xaplanteris, MD, PhD, of the Cardiovascular Center at Aalst, Belgium, presented the final 5-year follow-up of FAME 2 (the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2) trial, in which 888 patients with stable CAD and at least one hemodynamically significant coronary stenosis as defined by an FFR value of 0.80 or less in a major artery were randomized to FFR-guided PCI plus guideline-directed medical therapy or to medical therapy alone.
The long-term favorable impact of the early interventional strategy was striking: At 5 years, the rate of the primary composite endpoint of death, MI, or urgent revascularization was 13.9% in the early PCI group, roughly half of the 27% rate in the medically managed group. And this intention-to-treat analysis understates the true benefit of early PCI, since by the 5-year mark fully 51% of patients in the medically managed arm had crossed over to PCI.
The difference in the composite endpoint was driven largely by the early PCI group’s lesser need for urgent revascularization, defined as revascularization performed during any unplanned hospital admission for symptoms prompting revascularization. Most of these urgent revascularizations were prompted by in-hospital positive cardiac biomarkers, ECG changes, or unstable angina.
An important finding that was not apparent during shorter-term follow-up is that, by the 5-year mark, the early PCI strategy conferred a significant reduction in the risk of acute MI: 8.1% versus 12%. This difference was mainly due to the early PCI group’s lower rate of nonprocedurally related spontaneous MI: 6.5% compared with 10.2% in the control group, for a 38% relative risk reduction.
Discussant Philip Urban, MD, director of interventional cardiology at Hospital de la Tour in Geneva, said the take-home message from FAME 2 for him was simple: “If it ain’t broke, don’t fix it; but if it is, don’t procrastinate.”
Martin B. Leon, MD, observed that, up until now, when he has discussed with patients who have stable CAD the possibility of undergoing PCI, he has described the potential benefits as being reduced ischemia and improved symptoms with no significant impact on the hard endpoints of acute MI or death. FAME 2 has changed all that.
“What I really enjoyed about this presentation is that you dissected the improvement and demonstrated clearly that spontaneous MIs are in fact reduced with PCI in patients with stable CAD, which is a hard endpoint. And I would even argue that yours is a minimalistic analysis in the sense that many of the urgent revascularization patients likely would have ended up being nontransmural MIs as well. So I think this gives credence to the understanding that PCI not only affects ischemia but also affects the hard endpoint of spontaneous MI. And you need a large study like this with a 5-year endpoint to clarify those issues,” noted Dr. Leon, professor of medicine at Columbia University in New York.
ORBITA revisited
ORBITA was the first-ever randomized blinded trial of real versus sham PCI in patients with stable CAD. When Rasha Al-Lamee, MD, presented the primary results at the TCT 2017 conference in Denver, reporting that PCI failed to show a significant improvement in exercise time compared with placebo PCI, reaction was swift and furious. Interventionalists criticized the study’s choice of treadmill exercise time as an inappropriately squishy primary endpoint. Noninterventionalists saw ORBITA as confirming their view that many interventional cardiologists are catheter cowboys.
However, with additional time for further data analysis, Dr. Al-Lamee reported at EuroPCR 2018 that, in fact, the degree of ischemia seen on baseline iFR and FFR entirely predicted the extent of objective improvement in ischemia on dobutamine stress echocardiography in response to PCI. The 25% of participants whose iFR and FFR were greater than the generally accepted thresholds for intervention did not derive any significant placebo-subtracted benefit from PCI. In contrast, the lower the baseline FFR and iFR values – meaning the greater the impairment of blood flow across a stenotic lesion – the greater the reduction in ischemia in response to true PCI.
Of note, at the end of the 6-week blinded study period, 85% of patients in the control group opted for PCI.
“This is the trial everyone is talking about. Even on Twitter, it’s really dominating,” observed discussant Davide Capodanno, MD, PhD, of the University of Catania, Italy. “And this new freedom from angina endpoint, this is a win for PCI.”
Asked what she would do differently if she could do ORBITA over again, Dr. Al-Lamee didn’t hesitate: “If I were to do it again, I absolutely agree that exercise time would not be the primary endpoint I would choose.”
SCAAR
Elmir Omerovic, MD, PhD, presented an update from the long-running observational prospective Swedish national registry. The analysis included 3,460 patients who underwent PCI for stable angina with FFR and/or iFR guidance and 21,221 others whose PCI was performed based solely on coronary angiography.
At the beginning of the 10-year study period, FFR/iFR was utilized in 5%-6% of PCIs for stable CAD; today that rate has climbed to 40%, according to the cardiologist.
He reported no financial conflicts of interest regarding his study.
Simultaneously with Dr. Xaplanteris’ presentation of the final 5-year outcomes of FAME 2, the results were published online (N Engl J Med. 2018 May 22. doi: 10.1056/NEJMoa1803538). He reported having no financial conflicts of interest.
Similarly, Dr. Al-Lamee’s updated analysis of ORBITA was simultaneously published (Circulation. 2018 May 22. doi: 10.11161/CIRCULATIONAHA.118.033801). She, too, reported having no financial conflicts regarding this investigator-initiated study.
Dr. Haude expressed confidence that these studies will result in significant changes in the next iteration of the European Society of Cardiology guidelines on chronic coronary syndrome, likely to be issued in 2019 or 2020.
REPORTING FROM EUROPCR 2018
Spotlight on nonmelanoma skin cancer’s true burden
CHICAGO – The true extent of the burden imposed by nonmelanoma skin cancer remains widely underappreciated by health policy makers, the public, employers, and nondermatologist physicians, Marta J. Van Beek, MD, asserted at the annual meeting of the American College of Mohs Surgery.
It’s very much in the interest of Mohs surgeons, as the experts in cutaneous malignancies, to get the accurate message out, she added.
Abundant evidence indicates there is an ongoing epidemic of nonmelanoma skin cancer (NMSC) in the United States – and it is associated with a surprising amount of morbidity and mortality, the dermatologic surgeon observed.
For example, while the American Academy of Dermatology’s 93-page Burden of Skin Disease report identified melanoma as the No. 1 cause of mortality because of skin disease – no surprise there – what may come as news to many is that NMSC was No. 2, accounting for 4,376 deaths in 2013, or 19% of the total. That’s more deaths than occurred because of wounds and burns.
And while the number of cases of NMSC is going up year after year as the population ages, it’s also the case that patients with complex NMSC are developing it at a younger and younger age. As documented in the AAD’s DataDerm registry encompassing more than 6 million patients seen by dermatologists during 2015-2017, well over 20,000 patients who underwent Mohs micrographic surgery for NMSC were aged 45-55 years, and another 60,000 were aged 55-65 years. That being said, Mohs surgery was used to treat 477,365 NMSCs in 318,933 patients included in DataDerm during 2015-2017, and in that population, basal cell carcinomas outnumbered squamous cell carcinomas 2:1.
An interesting aspect of the burden imparted by NMSC is that patients with NMSC have a higher risk of other types of cancer, and when they develop those other primary cancers they tend to do more poorly than cancer patients without a history of NMSC, Dr. Van Beek continued.
She cited a comprehensive study by investigators at the Medical University of South Carolina, Charleston, who concluded that the odds of developing a noncutaneous second primary malignancy were 27% greater in individuals with a history of NMSC than in those without such a history. The increased risk was statistically significant for 26 types of noncutaneous cancer, consistent in both men and women, and the younger a patient’s age at onset of NMSC, the stronger the association with noncutaneous cancers (Adv Cancer Res. 2016;130:257-91).
In a separate systematic review by some of the same investigators, patients with a history of squamous cell carcinoma were at a 30% increased risk of all-cause mortality and 117% greater cancer-specific mortality than those without a history of the disease. The associations were less potent for basal cell carcinoma (Arch Dermatol Res. 2017 May;309[4]:243-51).
“You are more likely to die of your nonskin cancer if you’ve ever had a skin cancer, regardless of what that other cancer is. This may mean that once you have a skin cancer, maybe that proves you have poor protoplasm that makes you more prone to other cancers, but even if that’s the case I think it demonstrates that nonmelanoma skin cancer has a substantial contribution to morbidity and mortality outside of what we normally think about,” Dr. Van Beek said.
Another underappreciated aspect of the burden of NMSC is what economists call lost opportunity cost. This isn’t the direct medical cost, but work time missed because of disease. In 2013, according to the AAD Burden of Skin Disease report, melanoma was responsible for $88 million worth of lost productivity, while for NMSC, the figure was $376 million.
“When you’re talking about the burden of disease, it’s important to actually talk to employers about how important it is to pay for the treatment of skin cancer because that keeps people at work and productive,” the dermatologist said.
Investigators for the World Health Organization’s Global Burden of Disease project estimate that the total years lost to disability for patients with NMSC are comparable with the figures for patients with thyroid, esophageal, or ovarian cancer, Dr. Van Beek noted.
Payers and health policy makers are unnerved by the growing utilization of Mohs surgery, she warned.
“This is really important: If you want to substantiate our utilization, you have to make policy makers understand that we are doing this because more people have skin cancer,” she emphasized.
Dr. Van Beek reported no financial conflicts regarding her presentation.
CHICAGO – The true extent of the burden imposed by nonmelanoma skin cancer remains widely underappreciated by health policy makers, the public, employers, and nondermatologist physicians, Marta J. Van Beek, MD, asserted at the annual meeting of the American College of Mohs Surgery.
It’s very much in the interest of Mohs surgeons, as the experts in cutaneous malignancies, to get the accurate message out, she added.
Abundant evidence indicates there is an ongoing epidemic of nonmelanoma skin cancer (NMSC) in the United States – and it is associated with a surprising amount of morbidity and mortality, the dermatologic surgeon observed.
For example, while the American Academy of Dermatology’s 93-page Burden of Skin Disease report identified melanoma as the No. 1 cause of mortality because of skin disease – no surprise there – what may come as news to many is that NMSC was No. 2, accounting for 4,376 deaths in 2013, or 19% of the total. That’s more deaths than occurred because of wounds and burns.
And while the number of cases of NMSC is going up year after year as the population ages, it’s also the case that patients with complex NMSC are developing it at a younger and younger age. As documented in the AAD’s DataDerm registry encompassing more than 6 million patients seen by dermatologists during 2015-2017, well over 20,000 patients who underwent Mohs micrographic surgery for NMSC were aged 45-55 years, and another 60,000 were aged 55-65 years. That being said, Mohs surgery was used to treat 477,365 NMSCs in 318,933 patients included in DataDerm during 2015-2017, and in that population, basal cell carcinomas outnumbered squamous cell carcinomas 2:1.
An interesting aspect of the burden imparted by NMSC is that patients with NMSC have a higher risk of other types of cancer, and when they develop those other primary cancers they tend to do more poorly than cancer patients without a history of NMSC, Dr. Van Beek continued.
She cited a comprehensive study by investigators at the Medical University of South Carolina, Charleston, who concluded that the odds of developing a noncutaneous second primary malignancy were 27% greater in individuals with a history of NMSC than in those without such a history. The increased risk was statistically significant for 26 types of noncutaneous cancer, consistent in both men and women, and the younger a patient’s age at onset of NMSC, the stronger the association with noncutaneous cancers (Adv Cancer Res. 2016;130:257-91).
In a separate systematic review by some of the same investigators, patients with a history of squamous cell carcinoma were at a 30% increased risk of all-cause mortality and 117% greater cancer-specific mortality than those without a history of the disease. The associations were less potent for basal cell carcinoma (Arch Dermatol Res. 2017 May;309[4]:243-51).
“You are more likely to die of your nonskin cancer if you’ve ever had a skin cancer, regardless of what that other cancer is. This may mean that once you have a skin cancer, maybe that proves you have poor protoplasm that makes you more prone to other cancers, but even if that’s the case I think it demonstrates that nonmelanoma skin cancer has a substantial contribution to morbidity and mortality outside of what we normally think about,” Dr. Van Beek said.
Another underappreciated aspect of the burden of NMSC is what economists call lost opportunity cost. This isn’t the direct medical cost, but work time missed because of disease. In 2013, according to the AAD Burden of Skin Disease report, melanoma was responsible for $88 million worth of lost productivity, while for NMSC, the figure was $376 million.
“When you’re talking about the burden of disease, it’s important to actually talk to employers about how important it is to pay for the treatment of skin cancer because that keeps people at work and productive,” the dermatologist said.
Investigators for the World Health Organization’s Global Burden of Disease project estimate that the total years lost to disability for patients with NMSC are comparable with the figures for patients with thyroid, esophageal, or ovarian cancer, Dr. Van Beek noted.
Payers and health policy makers are unnerved by the growing utilization of Mohs surgery, she warned.
“This is really important: If you want to substantiate our utilization, you have to make policy makers understand that we are doing this because more people have skin cancer,” she emphasized.
Dr. Van Beek reported no financial conflicts regarding her presentation.
CHICAGO – The true extent of the burden imposed by nonmelanoma skin cancer remains widely underappreciated by health policy makers, the public, employers, and nondermatologist physicians, Marta J. Van Beek, MD, asserted at the annual meeting of the American College of Mohs Surgery.
It’s very much in the interest of Mohs surgeons, as the experts in cutaneous malignancies, to get the accurate message out, she added.
Abundant evidence indicates there is an ongoing epidemic of nonmelanoma skin cancer (NMSC) in the United States – and it is associated with a surprising amount of morbidity and mortality, the dermatologic surgeon observed.
For example, while the American Academy of Dermatology’s 93-page Burden of Skin Disease report identified melanoma as the No. 1 cause of mortality because of skin disease – no surprise there – what may come as news to many is that NMSC was No. 2, accounting for 4,376 deaths in 2013, or 19% of the total. That’s more deaths than occurred because of wounds and burns.
And while the number of cases of NMSC is going up year after year as the population ages, it’s also the case that patients with complex NMSC are developing it at a younger and younger age. As documented in the AAD’s DataDerm registry encompassing more than 6 million patients seen by dermatologists during 2015-2017, well over 20,000 patients who underwent Mohs micrographic surgery for NMSC were aged 45-55 years, and another 60,000 were aged 55-65 years. That being said, Mohs surgery was used to treat 477,365 NMSCs in 318,933 patients included in DataDerm during 2015-2017, and in that population, basal cell carcinomas outnumbered squamous cell carcinomas 2:1.
An interesting aspect of the burden imparted by NMSC is that patients with NMSC have a higher risk of other types of cancer, and when they develop those other primary cancers they tend to do more poorly than cancer patients without a history of NMSC, Dr. Van Beek continued.
She cited a comprehensive study by investigators at the Medical University of South Carolina, Charleston, who concluded that the odds of developing a noncutaneous second primary malignancy were 27% greater in individuals with a history of NMSC than in those without such a history. The increased risk was statistically significant for 26 types of noncutaneous cancer, consistent in both men and women, and the younger a patient’s age at onset of NMSC, the stronger the association with noncutaneous cancers (Adv Cancer Res. 2016;130:257-91).
In a separate systematic review by some of the same investigators, patients with a history of squamous cell carcinoma were at a 30% increased risk of all-cause mortality and 117% greater cancer-specific mortality than those without a history of the disease. The associations were less potent for basal cell carcinoma (Arch Dermatol Res. 2017 May;309[4]:243-51).
“You are more likely to die of your nonskin cancer if you’ve ever had a skin cancer, regardless of what that other cancer is. This may mean that once you have a skin cancer, maybe that proves you have poor protoplasm that makes you more prone to other cancers, but even if that’s the case I think it demonstrates that nonmelanoma skin cancer has a substantial contribution to morbidity and mortality outside of what we normally think about,” Dr. Van Beek said.
Another underappreciated aspect of the burden of NMSC is what economists call lost opportunity cost. This isn’t the direct medical cost, but work time missed because of disease. In 2013, according to the AAD Burden of Skin Disease report, melanoma was responsible for $88 million worth of lost productivity, while for NMSC, the figure was $376 million.
“When you’re talking about the burden of disease, it’s important to actually talk to employers about how important it is to pay for the treatment of skin cancer because that keeps people at work and productive,” the dermatologist said.
Investigators for the World Health Organization’s Global Burden of Disease project estimate that the total years lost to disability for patients with NMSC are comparable with the figures for patients with thyroid, esophageal, or ovarian cancer, Dr. Van Beek noted.
Payers and health policy makers are unnerved by the growing utilization of Mohs surgery, she warned.
“This is really important: If you want to substantiate our utilization, you have to make policy makers understand that we are doing this because more people have skin cancer,” she emphasized.
Dr. Van Beek reported no financial conflicts regarding her presentation.
EXPERT ANALYSIS FROM THE ACMS ANNUAL MEETING
Breakthrough in noninvasive assessment of multivessel CAD
PARIS – A completely noninvasive method of identifying functionally significant lesions in patients with triple-vessel coronary artery disease yielded results comparable to conventional invasive angiographic assessment accompanied by an intracoronary pressure wire, in a prespecified secondary analysis of the SYNTAX II study.
That noninvasive method uses fractional flow reserve calculated from computed tomographic angiography, Carlos Collet, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
The results were hailed as a harbinger of a coming era in which interventional decision making will be based entirely upon noninvasively acquired anatomic and physiologic data. Conventional diagnostic angiography is predicted to fall by the wayside, with resultant savings in time and cost as well as avoidance of the risks of percutaneous diagnostic angiography, which entails considerably more radiation exposure than does noninvasive CT angiography (CTA).
“We are on the verge of a major change,” said Patrick W. Serruys, MD, PhD, professor of cardiology at Imperial College London, who was the senior coinvestigator in the study. “I think that the next disruptive moment in cardiology will be the introduction of the new generation of multislice CT scans replacing conventional cineangiography in the next 5-10 years. For the interventional cardiologist, to have the results of a multislice CT scan the day before a procedure is a wonderful bonus. You know in advance what you’re going to see, you can develop your treatment strategy, and you can spare contrast.”
Compared with conventional invasive angiographic assessment with the use of an intracoronary pressure wire to measure iFR, the noninvasively calculated SYNTAX II score had 95% sensitivity and 61% specificity for detection of functionally significant stenosis, with a positive predictive value of 81% and a negative predictive value of 87%. And this was achieved using older scanners and software considerably less accurate than today’s rapidly evolving state of the art, Dr. Collet noted.
Background
The original landmark SYNTAX trial led to development of an anatomically based SYNTAX score for use in stratifying risk and guiding treatment planning – coronary artery bypass grafting versus PCI – in patients with multivessel CAD. Both the U.S. and European guidelines recommend the use of this score, based on invasive angiography, giving it a Class IIa and I recommendation, respectively. Patients with a low-risk SYNTAX score of 22 or less were shown to have similar outcomes with PCI and coronary artery bypass grafting, while those with a score of 23 or more had better outcomes at 5-year follow-up with CABG.
Subsequently, incorporation of clinical characteristics formed the basis of the updated SYNTAX II score, with enhanced predictive accuracy allowing for projections of 4-year all-cause mortality with CABG versus PCI in a given patient (www.syntaxscore.com). The new SYNTAX II substudy takes things a giant step further by rendering the coronary imaging and physiology assessment noninvasive.
Simultaneous with Dr. Collet’s presentation at EuroPCR 2018, the study results were published in the Journal of the American College of Cardiology.
In an accompanying editorial, Bjarne L. Norgaard, MD, PhD, of Aarhus (Denmark) University and coauthors enthused, “These data suggest that we may be entering a new era in the management of CAD. The days of having patients entering the catheterization laboratory with nothing more than symptoms and a positive stress test result may be coming to an end. This study may be signaling a shifting paradigm in which CAD is diagnosed and thoroughly characterized noninvasively, and revascularization planning made in a collaborative fashion integrating the heart team, and a wealth of noninvasive data that will hopefully lead to more effective and cost-efficient revascularization strategies.”
What’s next
Elsewhere at EuroPCR 2018, Dr. Serruys presented the results of the SYNTAX III Revolution Trial, which randomized six pairs of heart teams – each comprising an interventional cardiologist, surgeon, and radiologist – to collectively assess and plan revascularization strategies for 223 patients with left main or triple-vessel CAD. One heart team in each pair was provided with a patient’s noninvasive CTA and FFR results, while the other team was given only the results of conventional angiography.
“There was almost perfect agreement between the heart teams on their decisions,” according to Dr. Serruys. “We were impressed that the surgeons were enthusiastic about the prospect of operating based on multislice CT alone.
On the basis of this evidence that heart teams found, the noninvasive assessment to be acceptable, he and his coinvestigators are organizing a multicenter trial to assess the feasibility and safety of the fully noninvasive stratification, compared with conventional angiography and invasive physiologic assessment of lesions. The primary safety endpoint will be the 1-month patency of bypass grafts.
The multislice scanner used in the SYNTAX III Revolution trial was the General Electric Revolution CT scanner, which enables imaging of the heart during a single heart beat. But Dr. Serruys said most of the big medical imaging companies with an eye to the near future are now developing multislice scanners specifically for the heart.
“They cost half the price and take only half the space of conventional scanners. I think these small units – which are not used for the brain, the abdomen, and all the rest – are going to play a big role in cardiology,” he predicted.
William Wijns, MD, codirector of EuroPCR, called the results of the SYNTAX II and SYNTAX III Revolution studies “transformative.” He and the other meeting organizers highlighted the studies in a special “deep-dive” session, which he urged younger interventionalists in particular to attend because he believes it’s likely they will be relying on these noninvasive assessments in the near future.
The SYNTAX III Revolution trial was sponsored by the European Cardiovascular Research Institute with support from GE Healthcare and HeartFlow. Dr. Serruys reported having no financial relationship with either company.
SOURCE: Collet C. EuroPCR 2018, Simultaneous publication (J Am Coll Cardiol 2018;71:40-53).
PARIS – A completely noninvasive method of identifying functionally significant lesions in patients with triple-vessel coronary artery disease yielded results comparable to conventional invasive angiographic assessment accompanied by an intracoronary pressure wire, in a prespecified secondary analysis of the SYNTAX II study.
That noninvasive method uses fractional flow reserve calculated from computed tomographic angiography, Carlos Collet, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
The results were hailed as a harbinger of a coming era in which interventional decision making will be based entirely upon noninvasively acquired anatomic and physiologic data. Conventional diagnostic angiography is predicted to fall by the wayside, with resultant savings in time and cost as well as avoidance of the risks of percutaneous diagnostic angiography, which entails considerably more radiation exposure than does noninvasive CT angiography (CTA).
“We are on the verge of a major change,” said Patrick W. Serruys, MD, PhD, professor of cardiology at Imperial College London, who was the senior coinvestigator in the study. “I think that the next disruptive moment in cardiology will be the introduction of the new generation of multislice CT scans replacing conventional cineangiography in the next 5-10 years. For the interventional cardiologist, to have the results of a multislice CT scan the day before a procedure is a wonderful bonus. You know in advance what you’re going to see, you can develop your treatment strategy, and you can spare contrast.”
Compared with conventional invasive angiographic assessment with the use of an intracoronary pressure wire to measure iFR, the noninvasively calculated SYNTAX II score had 95% sensitivity and 61% specificity for detection of functionally significant stenosis, with a positive predictive value of 81% and a negative predictive value of 87%. And this was achieved using older scanners and software considerably less accurate than today’s rapidly evolving state of the art, Dr. Collet noted.
Background
The original landmark SYNTAX trial led to development of an anatomically based SYNTAX score for use in stratifying risk and guiding treatment planning – coronary artery bypass grafting versus PCI – in patients with multivessel CAD. Both the U.S. and European guidelines recommend the use of this score, based on invasive angiography, giving it a Class IIa and I recommendation, respectively. Patients with a low-risk SYNTAX score of 22 or less were shown to have similar outcomes with PCI and coronary artery bypass grafting, while those with a score of 23 or more had better outcomes at 5-year follow-up with CABG.
Subsequently, incorporation of clinical characteristics formed the basis of the updated SYNTAX II score, with enhanced predictive accuracy allowing for projections of 4-year all-cause mortality with CABG versus PCI in a given patient (www.syntaxscore.com). The new SYNTAX II substudy takes things a giant step further by rendering the coronary imaging and physiology assessment noninvasive.
Simultaneous with Dr. Collet’s presentation at EuroPCR 2018, the study results were published in the Journal of the American College of Cardiology.
In an accompanying editorial, Bjarne L. Norgaard, MD, PhD, of Aarhus (Denmark) University and coauthors enthused, “These data suggest that we may be entering a new era in the management of CAD. The days of having patients entering the catheterization laboratory with nothing more than symptoms and a positive stress test result may be coming to an end. This study may be signaling a shifting paradigm in which CAD is diagnosed and thoroughly characterized noninvasively, and revascularization planning made in a collaborative fashion integrating the heart team, and a wealth of noninvasive data that will hopefully lead to more effective and cost-efficient revascularization strategies.”
What’s next
Elsewhere at EuroPCR 2018, Dr. Serruys presented the results of the SYNTAX III Revolution Trial, which randomized six pairs of heart teams – each comprising an interventional cardiologist, surgeon, and radiologist – to collectively assess and plan revascularization strategies for 223 patients with left main or triple-vessel CAD. One heart team in each pair was provided with a patient’s noninvasive CTA and FFR results, while the other team was given only the results of conventional angiography.
“There was almost perfect agreement between the heart teams on their decisions,” according to Dr. Serruys. “We were impressed that the surgeons were enthusiastic about the prospect of operating based on multislice CT alone.
On the basis of this evidence that heart teams found, the noninvasive assessment to be acceptable, he and his coinvestigators are organizing a multicenter trial to assess the feasibility and safety of the fully noninvasive stratification, compared with conventional angiography and invasive physiologic assessment of lesions. The primary safety endpoint will be the 1-month patency of bypass grafts.
The multislice scanner used in the SYNTAX III Revolution trial was the General Electric Revolution CT scanner, which enables imaging of the heart during a single heart beat. But Dr. Serruys said most of the big medical imaging companies with an eye to the near future are now developing multislice scanners specifically for the heart.
“They cost half the price and take only half the space of conventional scanners. I think these small units – which are not used for the brain, the abdomen, and all the rest – are going to play a big role in cardiology,” he predicted.
William Wijns, MD, codirector of EuroPCR, called the results of the SYNTAX II and SYNTAX III Revolution studies “transformative.” He and the other meeting organizers highlighted the studies in a special “deep-dive” session, which he urged younger interventionalists in particular to attend because he believes it’s likely they will be relying on these noninvasive assessments in the near future.
The SYNTAX III Revolution trial was sponsored by the European Cardiovascular Research Institute with support from GE Healthcare and HeartFlow. Dr. Serruys reported having no financial relationship with either company.
SOURCE: Collet C. EuroPCR 2018, Simultaneous publication (J Am Coll Cardiol 2018;71:40-53).
PARIS – A completely noninvasive method of identifying functionally significant lesions in patients with triple-vessel coronary artery disease yielded results comparable to conventional invasive angiographic assessment accompanied by an intracoronary pressure wire, in a prespecified secondary analysis of the SYNTAX II study.
That noninvasive method uses fractional flow reserve calculated from computed tomographic angiography, Carlos Collet, MD, said at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.
The results were hailed as a harbinger of a coming era in which interventional decision making will be based entirely upon noninvasively acquired anatomic and physiologic data. Conventional diagnostic angiography is predicted to fall by the wayside, with resultant savings in time and cost as well as avoidance of the risks of percutaneous diagnostic angiography, which entails considerably more radiation exposure than does noninvasive CT angiography (CTA).
“We are on the verge of a major change,” said Patrick W. Serruys, MD, PhD, professor of cardiology at Imperial College London, who was the senior coinvestigator in the study. “I think that the next disruptive moment in cardiology will be the introduction of the new generation of multislice CT scans replacing conventional cineangiography in the next 5-10 years. For the interventional cardiologist, to have the results of a multislice CT scan the day before a procedure is a wonderful bonus. You know in advance what you’re going to see, you can develop your treatment strategy, and you can spare contrast.”
Compared with conventional invasive angiographic assessment with the use of an intracoronary pressure wire to measure iFR, the noninvasively calculated SYNTAX II score had 95% sensitivity and 61% specificity for detection of functionally significant stenosis, with a positive predictive value of 81% and a negative predictive value of 87%. And this was achieved using older scanners and software considerably less accurate than today’s rapidly evolving state of the art, Dr. Collet noted.
Background
The original landmark SYNTAX trial led to development of an anatomically based SYNTAX score for use in stratifying risk and guiding treatment planning – coronary artery bypass grafting versus PCI – in patients with multivessel CAD. Both the U.S. and European guidelines recommend the use of this score, based on invasive angiography, giving it a Class IIa and I recommendation, respectively. Patients with a low-risk SYNTAX score of 22 or less were shown to have similar outcomes with PCI and coronary artery bypass grafting, while those with a score of 23 or more had better outcomes at 5-year follow-up with CABG.
Subsequently, incorporation of clinical characteristics formed the basis of the updated SYNTAX II score, with enhanced predictive accuracy allowing for projections of 4-year all-cause mortality with CABG versus PCI in a given patient (www.syntaxscore.com). The new SYNTAX II substudy takes things a giant step further by rendering the coronary imaging and physiology assessment noninvasive.
Simultaneous with Dr. Collet’s presentation at EuroPCR 2018, the study results were published in the Journal of the American College of Cardiology.
In an accompanying editorial, Bjarne L. Norgaard, MD, PhD, of Aarhus (Denmark) University and coauthors enthused, “These data suggest that we may be entering a new era in the management of CAD. The days of having patients entering the catheterization laboratory with nothing more than symptoms and a positive stress test result may be coming to an end. This study may be signaling a shifting paradigm in which CAD is diagnosed and thoroughly characterized noninvasively, and revascularization planning made in a collaborative fashion integrating the heart team, and a wealth of noninvasive data that will hopefully lead to more effective and cost-efficient revascularization strategies.”
What’s next
Elsewhere at EuroPCR 2018, Dr. Serruys presented the results of the SYNTAX III Revolution Trial, which randomized six pairs of heart teams – each comprising an interventional cardiologist, surgeon, and radiologist – to collectively assess and plan revascularization strategies for 223 patients with left main or triple-vessel CAD. One heart team in each pair was provided with a patient’s noninvasive CTA and FFR results, while the other team was given only the results of conventional angiography.
“There was almost perfect agreement between the heart teams on their decisions,” according to Dr. Serruys. “We were impressed that the surgeons were enthusiastic about the prospect of operating based on multislice CT alone.
On the basis of this evidence that heart teams found, the noninvasive assessment to be acceptable, he and his coinvestigators are organizing a multicenter trial to assess the feasibility and safety of the fully noninvasive stratification, compared with conventional angiography and invasive physiologic assessment of lesions. The primary safety endpoint will be the 1-month patency of bypass grafts.
The multislice scanner used in the SYNTAX III Revolution trial was the General Electric Revolution CT scanner, which enables imaging of the heart during a single heart beat. But Dr. Serruys said most of the big medical imaging companies with an eye to the near future are now developing multislice scanners specifically for the heart.
“They cost half the price and take only half the space of conventional scanners. I think these small units – which are not used for the brain, the abdomen, and all the rest – are going to play a big role in cardiology,” he predicted.
William Wijns, MD, codirector of EuroPCR, called the results of the SYNTAX II and SYNTAX III Revolution studies “transformative.” He and the other meeting organizers highlighted the studies in a special “deep-dive” session, which he urged younger interventionalists in particular to attend because he believes it’s likely they will be relying on these noninvasive assessments in the near future.
The SYNTAX III Revolution trial was sponsored by the European Cardiovascular Research Institute with support from GE Healthcare and HeartFlow. Dr. Serruys reported having no financial relationship with either company.
SOURCE: Collet C. EuroPCR 2018, Simultaneous publication (J Am Coll Cardiol 2018;71:40-53).
REPORTING FROM EUROPCR 2018
Key clinical point:
Major finding: A completely noninvasive method of identifying functionally significant lesions in patients with triple-vessel CAD by means of fractional flow reserve calculated from CT angiography yielded results comparable to conventional pressure-wire-based invasive angiographic assessment.
Study details: This prespecified secondary analysis of the SYNTAX II trial compared the results of noninvasive assessment of patients with triple-vessel CAD using FFR calculated from CT angiography with conventional angiography plus an invasive pressure wire.
Disclosures: The study was sponsored by the European Cardiovascular Research Institute with research grant support from Volcano and Boston Scientific. The presenter reported financial relationships with half a dozen medical device companies, but neither of those two.
Source: Collet C. EuroPCR 2018, simultaneous publication (J Am Coll Cardiol 2018;71:40-53).
Cemiplimab impresses in advanced CSCC
CHICAGO – The investigational programmed cell death protein 1 checkpoint inhibitor cemiplimab proved highly effective for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma in a phase 1 clinical trial, Michael R. Migden, MD, reported at the annual meeting of the American College of Mohs Surgery.
And this was no ordinary phase 1 study, he noted. Because there is no Food and Drug Administration–approved treatment for advanced cutaneous squamous cell carcinoma (CSCC), cemiplimab has been granted both Breakthrough Drug and Orphan Drug status by the FDA and the European Medicines Agency.
Given the likelihood that cemiplimab will receive expeditious regulatory approval to address this major unmet need, he offered his colleagues practical tips on its use, including information about the drug’s chief side effects as well as a heads-up regarding the importance of early recognition of the pseudoprogression phenomenon that can occur with the drug.
He predicted this fully human monoclonal antibody directed at programmed cell death protein 1 (PD-1) is going to be an important drug for Mohs surgeons.
“Immunotherapy is becoming increasingly relevant to micrographic surgery and dermatologic oncology practice and fellowship training. Care for larger, advanced CSCC falls within our scope of practice and we should play an essential role, inclusive of multidisciplinary care, in the management and follow-up of these patients,” asserted Dr. Migden, a dermatologic surgeon at the University of Texas MD Anderson Cancer Center, Houston.
The open-label, phase 1 study included seven patients with distant metastatic CSCC and nine with locally and/or regionally advanced disease. They were treated with 3 mg/kg IV cemiplimab every 2 weeks for 48 weeks, with Response Evaluation Criteria In Solid Tumors 1.1 criteria used for assessment of response status every 8 weeks. More than 80% of the tumors were located in the head and neck. The great majority of study participants had previously been treated with radiation therapy and systemic agents, to little effect.
The complete response rate at 48 weeks was 12.5%, with tumor clearance occurring as quickly as 14 weeks. Another 25% of patients had a partial response, for an overall response rate of 37.5%. But that’s not the full success story, as another 31% of patients had stable disease. Thus, 11 of 16 patients, or 69%, experienced disease control.
“A disease-control rate of nearly 70% is really important because these are patients with life-threatening tumors. To be able to hold them steady is a big deal,” Dr. Migden observed.
One-quarter of study participants experienced progressive disease. The remainder weren’t evaluated for various reasons.
The dermatologist pointed out that locally advanced disease was particularly responsive to cemiplimab, with four of nine affected patients experiencing complete or partial response, for an overall response rate of 44%. This is consistent with the preliminary results of the pivotal phase 2 study, in which the overall response rate in the 78 participants with unresectable, locally advanced CSCC was 46%.
The phase 2 trial also includes another 59 patients with metastatic CSCC on 3 mg/kg IV cemiplimab every 14 days, as well as 56 patients with metastatic disease assigned to flat-dose 350-mg IV cemiplimab every 21 days.
Treatment side effects
In the phase 1 study, immunotherapy with cemiplimab was far better tolerated than in traditional cancer chemotherapy. There were two grade 3 cases of elevated liver enzymes and one of arthralgia, but no significant fatigue or nausea and no hypothyroidism. However, judging from the cumulative experience accrued with the five PD-1 checkpoint inhibitors already approved for treatment of other cancers, one must be prepared to encounter hypothyroidism and other endocrinopathies, pneumonitis, hepatitis, and rashes.
“The clinician must have a very high index of suspicion for these immune-related adverse events and a low threshold to consult with colleagues in other specialties – pulmonary, endocrine, and medical oncology – for evaluation and management of these possible side effects. I tell all the patients who are on cemiplimab, ‘Any new anything – a slight cough, mild diarrhea – you’re coming in and you’re getting checked,’ ” according to Dr. Migden.
That being said, the majority of immune-related adverse events because of PD-1 inhibitors are mild to moderate. Of the few that reach grade 3 or above, most can be successfully managed by pausing or discontinuing anti–PD-1 therapy coupled with prompt initiation of immunosuppressive therapy, typically with high-dose steroids, he added.
Look sharp for pseudoprogression
Pseudoprogression is a phenomenon whereby immunotherapy results in inflammatory changes bringing about a temporary increase in tumor size that precedes tumor shrinkage. It’s uncommon, occurring in 3 of 16 patients in the phase 1 study. The mechanism probably involves tumor infiltration by massive numbers of activated T cells. And there is evidence from other PD-1 inhibitor studies in advanced cancers that pseudoprogression may actually be a marker for increased likelihood of survival beyond 1 year.
“Pseudoprogression is important to recognize because the patients you treat with cemiplimab can get worse before they get better,” the dermatologist explained. “So you don’t want to prematurely discontinue treatment because you’re misclassifying it as tumor progression.”
The rationale for anti-PD-1 therapy in CSCC
Tumors that express PD-1 bind to PD–ligand 1 on T cells, switching off T-cell mediated tumor destruction and thereby allowing the malignancy to thrive.
“Simplified, the strategy here is to interfere with the interaction at the T-cell off switch, either with an antibody to PD–ligand 1, such as atezolizumab [Tecentriq], or an antibody to the PD-1 receptor, where cemiplimab works. By turning off the off switch, we get a T cell fully on and attacking the tumor cell,” Dr. Migden said.
“The more the tumor mutation burden, the better immunotherapy works – and CSCC has the highest tumor mutation burden of any tumor type in the Cancer Genome Atlas, several times higher than melanoma. Interestingly, basal cell carcinoma has an even higher tumor mutation burden than CSCC, but it’s not part of the atlas,” he continued.
Although the proportion of CSCCs that are locally advanced hasn’t been well established, it’s clear that CSCC is the deadliest nonmelanoma skin cancer, accounting for 3,900-8,800 deaths annually in the United States.
The cemiplimab phase 1 and 2 clinical trials for CSCC were jointly sponsored by Regeneron and Sanofi. The monoclonal antibody is also being developed for treatment of myeloma and lung cancer. Dr. Migden reported receiving honoraria from Regeneron and Sanofi, as well as from Genentech, Lilly, Novartis, and Sun Pharmaceuticals.
CHICAGO – The investigational programmed cell death protein 1 checkpoint inhibitor cemiplimab proved highly effective for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma in a phase 1 clinical trial, Michael R. Migden, MD, reported at the annual meeting of the American College of Mohs Surgery.
And this was no ordinary phase 1 study, he noted. Because there is no Food and Drug Administration–approved treatment for advanced cutaneous squamous cell carcinoma (CSCC), cemiplimab has been granted both Breakthrough Drug and Orphan Drug status by the FDA and the European Medicines Agency.
Given the likelihood that cemiplimab will receive expeditious regulatory approval to address this major unmet need, he offered his colleagues practical tips on its use, including information about the drug’s chief side effects as well as a heads-up regarding the importance of early recognition of the pseudoprogression phenomenon that can occur with the drug.
He predicted this fully human monoclonal antibody directed at programmed cell death protein 1 (PD-1) is going to be an important drug for Mohs surgeons.
“Immunotherapy is becoming increasingly relevant to micrographic surgery and dermatologic oncology practice and fellowship training. Care for larger, advanced CSCC falls within our scope of practice and we should play an essential role, inclusive of multidisciplinary care, in the management and follow-up of these patients,” asserted Dr. Migden, a dermatologic surgeon at the University of Texas MD Anderson Cancer Center, Houston.
The open-label, phase 1 study included seven patients with distant metastatic CSCC and nine with locally and/or regionally advanced disease. They were treated with 3 mg/kg IV cemiplimab every 2 weeks for 48 weeks, with Response Evaluation Criteria In Solid Tumors 1.1 criteria used for assessment of response status every 8 weeks. More than 80% of the tumors were located in the head and neck. The great majority of study participants had previously been treated with radiation therapy and systemic agents, to little effect.
The complete response rate at 48 weeks was 12.5%, with tumor clearance occurring as quickly as 14 weeks. Another 25% of patients had a partial response, for an overall response rate of 37.5%. But that’s not the full success story, as another 31% of patients had stable disease. Thus, 11 of 16 patients, or 69%, experienced disease control.
“A disease-control rate of nearly 70% is really important because these are patients with life-threatening tumors. To be able to hold them steady is a big deal,” Dr. Migden observed.
One-quarter of study participants experienced progressive disease. The remainder weren’t evaluated for various reasons.
The dermatologist pointed out that locally advanced disease was particularly responsive to cemiplimab, with four of nine affected patients experiencing complete or partial response, for an overall response rate of 44%. This is consistent with the preliminary results of the pivotal phase 2 study, in which the overall response rate in the 78 participants with unresectable, locally advanced CSCC was 46%.
The phase 2 trial also includes another 59 patients with metastatic CSCC on 3 mg/kg IV cemiplimab every 14 days, as well as 56 patients with metastatic disease assigned to flat-dose 350-mg IV cemiplimab every 21 days.
Treatment side effects
In the phase 1 study, immunotherapy with cemiplimab was far better tolerated than in traditional cancer chemotherapy. There were two grade 3 cases of elevated liver enzymes and one of arthralgia, but no significant fatigue or nausea and no hypothyroidism. However, judging from the cumulative experience accrued with the five PD-1 checkpoint inhibitors already approved for treatment of other cancers, one must be prepared to encounter hypothyroidism and other endocrinopathies, pneumonitis, hepatitis, and rashes.
“The clinician must have a very high index of suspicion for these immune-related adverse events and a low threshold to consult with colleagues in other specialties – pulmonary, endocrine, and medical oncology – for evaluation and management of these possible side effects. I tell all the patients who are on cemiplimab, ‘Any new anything – a slight cough, mild diarrhea – you’re coming in and you’re getting checked,’ ” according to Dr. Migden.
That being said, the majority of immune-related adverse events because of PD-1 inhibitors are mild to moderate. Of the few that reach grade 3 or above, most can be successfully managed by pausing or discontinuing anti–PD-1 therapy coupled with prompt initiation of immunosuppressive therapy, typically with high-dose steroids, he added.
Look sharp for pseudoprogression
Pseudoprogression is a phenomenon whereby immunotherapy results in inflammatory changes bringing about a temporary increase in tumor size that precedes tumor shrinkage. It’s uncommon, occurring in 3 of 16 patients in the phase 1 study. The mechanism probably involves tumor infiltration by massive numbers of activated T cells. And there is evidence from other PD-1 inhibitor studies in advanced cancers that pseudoprogression may actually be a marker for increased likelihood of survival beyond 1 year.
“Pseudoprogression is important to recognize because the patients you treat with cemiplimab can get worse before they get better,” the dermatologist explained. “So you don’t want to prematurely discontinue treatment because you’re misclassifying it as tumor progression.”
The rationale for anti-PD-1 therapy in CSCC
Tumors that express PD-1 bind to PD–ligand 1 on T cells, switching off T-cell mediated tumor destruction and thereby allowing the malignancy to thrive.
“Simplified, the strategy here is to interfere with the interaction at the T-cell off switch, either with an antibody to PD–ligand 1, such as atezolizumab [Tecentriq], or an antibody to the PD-1 receptor, where cemiplimab works. By turning off the off switch, we get a T cell fully on and attacking the tumor cell,” Dr. Migden said.
“The more the tumor mutation burden, the better immunotherapy works – and CSCC has the highest tumor mutation burden of any tumor type in the Cancer Genome Atlas, several times higher than melanoma. Interestingly, basal cell carcinoma has an even higher tumor mutation burden than CSCC, but it’s not part of the atlas,” he continued.
Although the proportion of CSCCs that are locally advanced hasn’t been well established, it’s clear that CSCC is the deadliest nonmelanoma skin cancer, accounting for 3,900-8,800 deaths annually in the United States.
The cemiplimab phase 1 and 2 clinical trials for CSCC were jointly sponsored by Regeneron and Sanofi. The monoclonal antibody is also being developed for treatment of myeloma and lung cancer. Dr. Migden reported receiving honoraria from Regeneron and Sanofi, as well as from Genentech, Lilly, Novartis, and Sun Pharmaceuticals.
CHICAGO – The investigational programmed cell death protein 1 checkpoint inhibitor cemiplimab proved highly effective for the treatment of locally advanced or metastatic cutaneous squamous cell carcinoma in a phase 1 clinical trial, Michael R. Migden, MD, reported at the annual meeting of the American College of Mohs Surgery.
And this was no ordinary phase 1 study, he noted. Because there is no Food and Drug Administration–approved treatment for advanced cutaneous squamous cell carcinoma (CSCC), cemiplimab has been granted both Breakthrough Drug and Orphan Drug status by the FDA and the European Medicines Agency.
Given the likelihood that cemiplimab will receive expeditious regulatory approval to address this major unmet need, he offered his colleagues practical tips on its use, including information about the drug’s chief side effects as well as a heads-up regarding the importance of early recognition of the pseudoprogression phenomenon that can occur with the drug.
He predicted this fully human monoclonal antibody directed at programmed cell death protein 1 (PD-1) is going to be an important drug for Mohs surgeons.
“Immunotherapy is becoming increasingly relevant to micrographic surgery and dermatologic oncology practice and fellowship training. Care for larger, advanced CSCC falls within our scope of practice and we should play an essential role, inclusive of multidisciplinary care, in the management and follow-up of these patients,” asserted Dr. Migden, a dermatologic surgeon at the University of Texas MD Anderson Cancer Center, Houston.
The open-label, phase 1 study included seven patients with distant metastatic CSCC and nine with locally and/or regionally advanced disease. They were treated with 3 mg/kg IV cemiplimab every 2 weeks for 48 weeks, with Response Evaluation Criteria In Solid Tumors 1.1 criteria used for assessment of response status every 8 weeks. More than 80% of the tumors were located in the head and neck. The great majority of study participants had previously been treated with radiation therapy and systemic agents, to little effect.
The complete response rate at 48 weeks was 12.5%, with tumor clearance occurring as quickly as 14 weeks. Another 25% of patients had a partial response, for an overall response rate of 37.5%. But that’s not the full success story, as another 31% of patients had stable disease. Thus, 11 of 16 patients, or 69%, experienced disease control.
“A disease-control rate of nearly 70% is really important because these are patients with life-threatening tumors. To be able to hold them steady is a big deal,” Dr. Migden observed.
One-quarter of study participants experienced progressive disease. The remainder weren’t evaluated for various reasons.
The dermatologist pointed out that locally advanced disease was particularly responsive to cemiplimab, with four of nine affected patients experiencing complete or partial response, for an overall response rate of 44%. This is consistent with the preliminary results of the pivotal phase 2 study, in which the overall response rate in the 78 participants with unresectable, locally advanced CSCC was 46%.
The phase 2 trial also includes another 59 patients with metastatic CSCC on 3 mg/kg IV cemiplimab every 14 days, as well as 56 patients with metastatic disease assigned to flat-dose 350-mg IV cemiplimab every 21 days.
Treatment side effects
In the phase 1 study, immunotherapy with cemiplimab was far better tolerated than in traditional cancer chemotherapy. There were two grade 3 cases of elevated liver enzymes and one of arthralgia, but no significant fatigue or nausea and no hypothyroidism. However, judging from the cumulative experience accrued with the five PD-1 checkpoint inhibitors already approved for treatment of other cancers, one must be prepared to encounter hypothyroidism and other endocrinopathies, pneumonitis, hepatitis, and rashes.
“The clinician must have a very high index of suspicion for these immune-related adverse events and a low threshold to consult with colleagues in other specialties – pulmonary, endocrine, and medical oncology – for evaluation and management of these possible side effects. I tell all the patients who are on cemiplimab, ‘Any new anything – a slight cough, mild diarrhea – you’re coming in and you’re getting checked,’ ” according to Dr. Migden.
That being said, the majority of immune-related adverse events because of PD-1 inhibitors are mild to moderate. Of the few that reach grade 3 or above, most can be successfully managed by pausing or discontinuing anti–PD-1 therapy coupled with prompt initiation of immunosuppressive therapy, typically with high-dose steroids, he added.
Look sharp for pseudoprogression
Pseudoprogression is a phenomenon whereby immunotherapy results in inflammatory changes bringing about a temporary increase in tumor size that precedes tumor shrinkage. It’s uncommon, occurring in 3 of 16 patients in the phase 1 study. The mechanism probably involves tumor infiltration by massive numbers of activated T cells. And there is evidence from other PD-1 inhibitor studies in advanced cancers that pseudoprogression may actually be a marker for increased likelihood of survival beyond 1 year.
“Pseudoprogression is important to recognize because the patients you treat with cemiplimab can get worse before they get better,” the dermatologist explained. “So you don’t want to prematurely discontinue treatment because you’re misclassifying it as tumor progression.”
The rationale for anti-PD-1 therapy in CSCC
Tumors that express PD-1 bind to PD–ligand 1 on T cells, switching off T-cell mediated tumor destruction and thereby allowing the malignancy to thrive.
“Simplified, the strategy here is to interfere with the interaction at the T-cell off switch, either with an antibody to PD–ligand 1, such as atezolizumab [Tecentriq], or an antibody to the PD-1 receptor, where cemiplimab works. By turning off the off switch, we get a T cell fully on and attacking the tumor cell,” Dr. Migden said.
“The more the tumor mutation burden, the better immunotherapy works – and CSCC has the highest tumor mutation burden of any tumor type in the Cancer Genome Atlas, several times higher than melanoma. Interestingly, basal cell carcinoma has an even higher tumor mutation burden than CSCC, but it’s not part of the atlas,” he continued.
Although the proportion of CSCCs that are locally advanced hasn’t been well established, it’s clear that CSCC is the deadliest nonmelanoma skin cancer, accounting for 3,900-8,800 deaths annually in the United States.
The cemiplimab phase 1 and 2 clinical trials for CSCC were jointly sponsored by Regeneron and Sanofi. The monoclonal antibody is also being developed for treatment of myeloma and lung cancer. Dr. Migden reported receiving honoraria from Regeneron and Sanofi, as well as from Genentech, Lilly, Novartis, and Sun Pharmaceuticals.
REPORTING FROM THE ACMS ANNUAL MEETING
Key clinical point:
Major finding: Disease control was achieved in 11 of 16 patients (69%).
Study details: The open-label, phase 1 study included seven patients with distant metastatic cutaneous squamous cell carcinoma and nine with locally and/or regionally advanced disease.
Disclosures: The cemiplimab phase 1 and 2 clinical trials for CSCC were jointly sponsored by Regeneron and Sanofi. Dr. Migden reported receiving honoraria from Regeneron and Sanofi as well as from Genentech, Lilly, Novartis, and Sun Pharmaceuticals.
Ropivacaine called top anesthesia for nail surgery
CHICAGO – Ropivacaine has a fast onset of action, longer duration than either lidocaine or bupivacaine, and it’s the only one of the three that’s inherently vasoconstrictive. For Brienne Cressey, MD, those features make ropivacaine the local anesthetic of choice in performing nail surgery.
“Local anesthesia is really key for nail surgery. If you don’t have good anesthesia it’s not a good experience for either the surgeon or the patient,” she observed at the annual meeting of the American College of Mohs Surgery.
Lidocaine has a fast onset – less than 1 minute – but a problematic short duration of 30-120 minutes. Bupivacaine has the disadvantage of a slow onset of up to 5 minutes, albeit with a longer duration of anesthesia at 2-4 hours. Ropivacaine has a fast onset, plus a duration of up to 8 hours. And unlike lidocaine and bupivacaine, which are vasodilatory, ropivacaine is vasoconstrictive.
“With lidocaine, you get a lot of blood right after you take off your tourniquet. With ropivacaine, you get really nice reperfusion, but it’s not too much. You take off the tourniquet, check to see you’ve got reperfusion, then you add a little ropivacaine – about 0.5 mL – on either side of the base of the distal phalanx. It stops the bleeding immediately and you can easily put on a pressure dressing. It’s a nice way to get the patient over the hump of those first hours of pain and lets them drive home in comfort,” explained Dr. Cressey, a dermatologist working in a group practice at Dermatology Professionals in East Greenwich, R.I.
Ropivacaine is less cardiotoxic than bupivacaine. And ropivacaine offers an additional advantage: Its pH is such that no buffering is necessary. “Ropivacaine doesn’t require any compounding. You can just use it at 1% straight out of the bottle. That’s what we do in our office, and we’ve had very good experience with it,” according to the dermatologist.
Achieving smooth sailing with local anesthesia
Dr. Cressey delivers ropivacaine slowly through a 30-gauge needle, which makes for a smaller, less painful puncture. She utilizes a topical cold spray, and places a vibrating machine as a distractant proximal to where she is injecting. She keeps the anesthetic at room temperature or warms it to body temperature in a water bath as another means of reducing the pain of injection.
The distal digital block
This is a cross between a traditional proximal digital block and a wing block. It works well for the second, third, and fourth digits, which are mostly volar dominant. The block bathes the volar nerve branch in anesthesia at the midline of the finger or toe.
Dr. Cressey begins by injecting ropivacaine proximal and lateral to the junction of the proximal nail fold and lateral nail fold. After creating a dermal wheal, she directs her needle perpendicularly downward toward the finger or toe pad, injecting 1-4 mL of anesthesia, depending upon digit size. Visible blanching will progress digitally. If resistance is encountered, it suggests the needle has penetrated a ligament or other fibrous tissue. Simply withdraw the needle and continue injecting.
“What’s nice about the distal digital block is you get an immediate effect, and there’s good hemostasis during the procedure as well,” she said.
Dr. Cressey reported no financial conflicts regarding her presentation.
CHICAGO – Ropivacaine has a fast onset of action, longer duration than either lidocaine or bupivacaine, and it’s the only one of the three that’s inherently vasoconstrictive. For Brienne Cressey, MD, those features make ropivacaine the local anesthetic of choice in performing nail surgery.
“Local anesthesia is really key for nail surgery. If you don’t have good anesthesia it’s not a good experience for either the surgeon or the patient,” she observed at the annual meeting of the American College of Mohs Surgery.
Lidocaine has a fast onset – less than 1 minute – but a problematic short duration of 30-120 minutes. Bupivacaine has the disadvantage of a slow onset of up to 5 minutes, albeit with a longer duration of anesthesia at 2-4 hours. Ropivacaine has a fast onset, plus a duration of up to 8 hours. And unlike lidocaine and bupivacaine, which are vasodilatory, ropivacaine is vasoconstrictive.
“With lidocaine, you get a lot of blood right after you take off your tourniquet. With ropivacaine, you get really nice reperfusion, but it’s not too much. You take off the tourniquet, check to see you’ve got reperfusion, then you add a little ropivacaine – about 0.5 mL – on either side of the base of the distal phalanx. It stops the bleeding immediately and you can easily put on a pressure dressing. It’s a nice way to get the patient over the hump of those first hours of pain and lets them drive home in comfort,” explained Dr. Cressey, a dermatologist working in a group practice at Dermatology Professionals in East Greenwich, R.I.
Ropivacaine is less cardiotoxic than bupivacaine. And ropivacaine offers an additional advantage: Its pH is such that no buffering is necessary. “Ropivacaine doesn’t require any compounding. You can just use it at 1% straight out of the bottle. That’s what we do in our office, and we’ve had very good experience with it,” according to the dermatologist.
Achieving smooth sailing with local anesthesia
Dr. Cressey delivers ropivacaine slowly through a 30-gauge needle, which makes for a smaller, less painful puncture. She utilizes a topical cold spray, and places a vibrating machine as a distractant proximal to where she is injecting. She keeps the anesthetic at room temperature or warms it to body temperature in a water bath as another means of reducing the pain of injection.
The distal digital block
This is a cross between a traditional proximal digital block and a wing block. It works well for the second, third, and fourth digits, which are mostly volar dominant. The block bathes the volar nerve branch in anesthesia at the midline of the finger or toe.
Dr. Cressey begins by injecting ropivacaine proximal and lateral to the junction of the proximal nail fold and lateral nail fold. After creating a dermal wheal, she directs her needle perpendicularly downward toward the finger or toe pad, injecting 1-4 mL of anesthesia, depending upon digit size. Visible blanching will progress digitally. If resistance is encountered, it suggests the needle has penetrated a ligament or other fibrous tissue. Simply withdraw the needle and continue injecting.
“What’s nice about the distal digital block is you get an immediate effect, and there’s good hemostasis during the procedure as well,” she said.
Dr. Cressey reported no financial conflicts regarding her presentation.
CHICAGO – Ropivacaine has a fast onset of action, longer duration than either lidocaine or bupivacaine, and it’s the only one of the three that’s inherently vasoconstrictive. For Brienne Cressey, MD, those features make ropivacaine the local anesthetic of choice in performing nail surgery.
“Local anesthesia is really key for nail surgery. If you don’t have good anesthesia it’s not a good experience for either the surgeon or the patient,” she observed at the annual meeting of the American College of Mohs Surgery.
Lidocaine has a fast onset – less than 1 minute – but a problematic short duration of 30-120 minutes. Bupivacaine has the disadvantage of a slow onset of up to 5 minutes, albeit with a longer duration of anesthesia at 2-4 hours. Ropivacaine has a fast onset, plus a duration of up to 8 hours. And unlike lidocaine and bupivacaine, which are vasodilatory, ropivacaine is vasoconstrictive.
“With lidocaine, you get a lot of blood right after you take off your tourniquet. With ropivacaine, you get really nice reperfusion, but it’s not too much. You take off the tourniquet, check to see you’ve got reperfusion, then you add a little ropivacaine – about 0.5 mL – on either side of the base of the distal phalanx. It stops the bleeding immediately and you can easily put on a pressure dressing. It’s a nice way to get the patient over the hump of those first hours of pain and lets them drive home in comfort,” explained Dr. Cressey, a dermatologist working in a group practice at Dermatology Professionals in East Greenwich, R.I.
Ropivacaine is less cardiotoxic than bupivacaine. And ropivacaine offers an additional advantage: Its pH is such that no buffering is necessary. “Ropivacaine doesn’t require any compounding. You can just use it at 1% straight out of the bottle. That’s what we do in our office, and we’ve had very good experience with it,” according to the dermatologist.
Achieving smooth sailing with local anesthesia
Dr. Cressey delivers ropivacaine slowly through a 30-gauge needle, which makes for a smaller, less painful puncture. She utilizes a topical cold spray, and places a vibrating machine as a distractant proximal to where she is injecting. She keeps the anesthetic at room temperature or warms it to body temperature in a water bath as another means of reducing the pain of injection.
The distal digital block
This is a cross between a traditional proximal digital block and a wing block. It works well for the second, third, and fourth digits, which are mostly volar dominant. The block bathes the volar nerve branch in anesthesia at the midline of the finger or toe.
Dr. Cressey begins by injecting ropivacaine proximal and lateral to the junction of the proximal nail fold and lateral nail fold. After creating a dermal wheal, she directs her needle perpendicularly downward toward the finger or toe pad, injecting 1-4 mL of anesthesia, depending upon digit size. Visible blanching will progress digitally. If resistance is encountered, it suggests the needle has penetrated a ligament or other fibrous tissue. Simply withdraw the needle and continue injecting.
“What’s nice about the distal digital block is you get an immediate effect, and there’s good hemostasis during the procedure as well,” she said.
Dr. Cressey reported no financial conflicts regarding her presentation.
EXPERT ANALYSIS FROM THE ACMS ANNUAL MEETING
How to choose between highly effective HBV therapies
MAUI, HAWAII – With three highly effective, guideline-recommended nucleoside/tide therapies for chronic hepatitis B virus (HBV) infection now available, the selection of the optimal antiviral agent for a given patient can seem daunting.
Norah Terrault, MD, offered guidance on this score at the Gastroenterology Updates, IBD, Liver Disease meeting.
As the current guidelines of the American Association for the Study of Liver Disease and European Association for the Study of the Liver make clear, these agents are to be used in targeting patients with active disease, defined by elevated alanine aminotransferase and HBV DNA levels and/or advanced fibrosis. These antivirals aim at long-term HBV control rather than disease cure.
Although numerous investigational drugs are in development with a focus on cure, the day of curative therapy has not yet arrived, noted Dr. Terrault, a professor of medicine and the director of the viral hepatitis center at the University of California, San Francisco.
Randomized trials presented at the 2017 annual meeting of European Association for the Study of the Liver demonstrated that the newest agent, tenofovir alafenamide (TAF), was as effective as tenofovir disoproxil fumarate (TDF) at suppressing HBV DNA through 96 weeks in both hepatitis B e-antigen (HBeAg)–negative and HBeAg-positive patients.
Moreover, TAF had a small but statistically significant advantage in terms of seroconversion rate at week 96 in the HBeAg-positive group, by a margin of 18%-12%. The alanine aminotransferase normalization rate was also significantly higher in the TAF group, by a margin of 81%-71% in HBeAg-negative patients and 75%-68% in HBeAg-positive patients.
“This [TAF] is a very good drug, a nice one to have at our disposal,” according to Dr. Terrault. “The primary reason we wanted it has to do with its safety profile.”
Its potential benefit in this regard was illustrated in a pair of multinational phase 3 clinical trials totaling nearly 1,300 patients with chronic HBV presented at the 2017 meeting of American Association for the Study of Liver Disease. After completing 96 weeks of double-blind treatment with TAF or TDF, everyone was switched to open-label TAF.
“There was a nice rebound in creatinine clearance and bone density when the switch was made from TDF to TAF,” she observed. “This is encouraging data for us, in that if you have a patient on TDF and you are concerned about renal or bone safety, you can do the switch to TAF and very quickly see some recovery in those abnormalities.”
Dr. Terrault offered the following guidance in selecting HBV therapy: For most patients with no comorbidities, monotherapy with either TAF, TDF, or entecavir is an excellent approach.
However, in a patient who has preexisting bone or renal disease – or who is at increased risk for such disease based upon age greater than 60 years, a history of fragility fractures, chronic systemic corticosteroid therapy, or renal abnormalities – entecavir or TAF is a better option than TDF.
TAF becomes the preferred choice over entecavir if the patient has previously been exposed to a nucleoside or if the patient is coinfected with HIV because the drug is approved for treatment of HIV and HBV, while entecavir is not.
Also, no dose adjustment of TAF is needed so long as the creatinine clearance is at least 15 mL/min, whereas the dose-adjustment threshold is 50 mL/min for both entecavir and TDF.
Conversely, entecavir, an older and less expensive drug than TAF, deserves priority in a patient with no prior exposure to a nucleoside, no HIV coinfection, or in an individual with a creatinine clearance below 15 mL/min after dose adjustment. TAF hasn’t been studied in patients with a creatinine clearance that low.
Also, TAF has not been studied in pregnant women or in patients with decompensated cirrhosis, the hepatologist noted.
Dr. Terrault serves as a consultant to AbbVie, Biotest, CoCrystal Pharmaceuticals, and Gilead Sciences.
MAUI, HAWAII – With three highly effective, guideline-recommended nucleoside/tide therapies for chronic hepatitis B virus (HBV) infection now available, the selection of the optimal antiviral agent for a given patient can seem daunting.
Norah Terrault, MD, offered guidance on this score at the Gastroenterology Updates, IBD, Liver Disease meeting.
As the current guidelines of the American Association for the Study of Liver Disease and European Association for the Study of the Liver make clear, these agents are to be used in targeting patients with active disease, defined by elevated alanine aminotransferase and HBV DNA levels and/or advanced fibrosis. These antivirals aim at long-term HBV control rather than disease cure.
Although numerous investigational drugs are in development with a focus on cure, the day of curative therapy has not yet arrived, noted Dr. Terrault, a professor of medicine and the director of the viral hepatitis center at the University of California, San Francisco.
Randomized trials presented at the 2017 annual meeting of European Association for the Study of the Liver demonstrated that the newest agent, tenofovir alafenamide (TAF), was as effective as tenofovir disoproxil fumarate (TDF) at suppressing HBV DNA through 96 weeks in both hepatitis B e-antigen (HBeAg)–negative and HBeAg-positive patients.
Moreover, TAF had a small but statistically significant advantage in terms of seroconversion rate at week 96 in the HBeAg-positive group, by a margin of 18%-12%. The alanine aminotransferase normalization rate was also significantly higher in the TAF group, by a margin of 81%-71% in HBeAg-negative patients and 75%-68% in HBeAg-positive patients.
“This [TAF] is a very good drug, a nice one to have at our disposal,” according to Dr. Terrault. “The primary reason we wanted it has to do with its safety profile.”
Its potential benefit in this regard was illustrated in a pair of multinational phase 3 clinical trials totaling nearly 1,300 patients with chronic HBV presented at the 2017 meeting of American Association for the Study of Liver Disease. After completing 96 weeks of double-blind treatment with TAF or TDF, everyone was switched to open-label TAF.
“There was a nice rebound in creatinine clearance and bone density when the switch was made from TDF to TAF,” she observed. “This is encouraging data for us, in that if you have a patient on TDF and you are concerned about renal or bone safety, you can do the switch to TAF and very quickly see some recovery in those abnormalities.”
Dr. Terrault offered the following guidance in selecting HBV therapy: For most patients with no comorbidities, monotherapy with either TAF, TDF, or entecavir is an excellent approach.
However, in a patient who has preexisting bone or renal disease – or who is at increased risk for such disease based upon age greater than 60 years, a history of fragility fractures, chronic systemic corticosteroid therapy, or renal abnormalities – entecavir or TAF is a better option than TDF.
TAF becomes the preferred choice over entecavir if the patient has previously been exposed to a nucleoside or if the patient is coinfected with HIV because the drug is approved for treatment of HIV and HBV, while entecavir is not.
Also, no dose adjustment of TAF is needed so long as the creatinine clearance is at least 15 mL/min, whereas the dose-adjustment threshold is 50 mL/min for both entecavir and TDF.
Conversely, entecavir, an older and less expensive drug than TAF, deserves priority in a patient with no prior exposure to a nucleoside, no HIV coinfection, or in an individual with a creatinine clearance below 15 mL/min after dose adjustment. TAF hasn’t been studied in patients with a creatinine clearance that low.
Also, TAF has not been studied in pregnant women or in patients with decompensated cirrhosis, the hepatologist noted.
Dr. Terrault serves as a consultant to AbbVie, Biotest, CoCrystal Pharmaceuticals, and Gilead Sciences.
MAUI, HAWAII – With three highly effective, guideline-recommended nucleoside/tide therapies for chronic hepatitis B virus (HBV) infection now available, the selection of the optimal antiviral agent for a given patient can seem daunting.
Norah Terrault, MD, offered guidance on this score at the Gastroenterology Updates, IBD, Liver Disease meeting.
As the current guidelines of the American Association for the Study of Liver Disease and European Association for the Study of the Liver make clear, these agents are to be used in targeting patients with active disease, defined by elevated alanine aminotransferase and HBV DNA levels and/or advanced fibrosis. These antivirals aim at long-term HBV control rather than disease cure.
Although numerous investigational drugs are in development with a focus on cure, the day of curative therapy has not yet arrived, noted Dr. Terrault, a professor of medicine and the director of the viral hepatitis center at the University of California, San Francisco.
Randomized trials presented at the 2017 annual meeting of European Association for the Study of the Liver demonstrated that the newest agent, tenofovir alafenamide (TAF), was as effective as tenofovir disoproxil fumarate (TDF) at suppressing HBV DNA through 96 weeks in both hepatitis B e-antigen (HBeAg)–negative and HBeAg-positive patients.
Moreover, TAF had a small but statistically significant advantage in terms of seroconversion rate at week 96 in the HBeAg-positive group, by a margin of 18%-12%. The alanine aminotransferase normalization rate was also significantly higher in the TAF group, by a margin of 81%-71% in HBeAg-negative patients and 75%-68% in HBeAg-positive patients.
“This [TAF] is a very good drug, a nice one to have at our disposal,” according to Dr. Terrault. “The primary reason we wanted it has to do with its safety profile.”
Its potential benefit in this regard was illustrated in a pair of multinational phase 3 clinical trials totaling nearly 1,300 patients with chronic HBV presented at the 2017 meeting of American Association for the Study of Liver Disease. After completing 96 weeks of double-blind treatment with TAF or TDF, everyone was switched to open-label TAF.
“There was a nice rebound in creatinine clearance and bone density when the switch was made from TDF to TAF,” she observed. “This is encouraging data for us, in that if you have a patient on TDF and you are concerned about renal or bone safety, you can do the switch to TAF and very quickly see some recovery in those abnormalities.”
Dr. Terrault offered the following guidance in selecting HBV therapy: For most patients with no comorbidities, monotherapy with either TAF, TDF, or entecavir is an excellent approach.
However, in a patient who has preexisting bone or renal disease – or who is at increased risk for such disease based upon age greater than 60 years, a history of fragility fractures, chronic systemic corticosteroid therapy, or renal abnormalities – entecavir or TAF is a better option than TDF.
TAF becomes the preferred choice over entecavir if the patient has previously been exposed to a nucleoside or if the patient is coinfected with HIV because the drug is approved for treatment of HIV and HBV, while entecavir is not.
Also, no dose adjustment of TAF is needed so long as the creatinine clearance is at least 15 mL/min, whereas the dose-adjustment threshold is 50 mL/min for both entecavir and TDF.
Conversely, entecavir, an older and less expensive drug than TAF, deserves priority in a patient with no prior exposure to a nucleoside, no HIV coinfection, or in an individual with a creatinine clearance below 15 mL/min after dose adjustment. TAF hasn’t been studied in patients with a creatinine clearance that low.
Also, TAF has not been studied in pregnant women or in patients with decompensated cirrhosis, the hepatologist noted.
Dr. Terrault serves as a consultant to AbbVie, Biotest, CoCrystal Pharmaceuticals, and Gilead Sciences.
EXPERT ANALYSIS FROM GUILD 2018
Patidegib, the first topical hedgehog inhibitor, scores in Gorlin syndrome
CHICAGO – in a phase 2 study, and did so without causing the problematic adverse events that prompt many Gorlin patients to discontinue systemic hedgehog inhibitor drugs, Ervin Epstein Jr., MD, said at the annual meeting of the American College of Mohs Surgery.
He characterized patidegib, a small-molecule cyclopamine derivative, as “a Goldilocks drug, a topical hedgehog inhibitor with percutaneous absorption that’s just right: sufficient to have anti-hedgehog and anti–basal cell carcinoma efficacy, but not enough to cause systemic exposure or systemic adverse events.”
A complete response – tumor clinical disappearance – occurred in 25% of the BCCs in the two active treatment arms. In contrast, none of the BCCs in the control group cleared. Patients on patidegib developed one or more new surgically eligible BCCs after study week 2 at a rate of 0.4 tumors per patient, markedly less than the rate of 1.4 tumors per patient in controls.
“We think that prevention is really the place to go with this drug,” said Dr. Epstein, cofounder and chief medical officer at PellePharm, the company based in Menlo Park, Calif., that is developing patidegib.
Indeed, he envisions patidegib gel as lifetime therapy for Gorlin patients.
Tumor shrinkage was significantly greater with 2% patidegib than with the 4% concentration. But so was treatment adherence: Patients in the 2% patidegib arm missed on average just 2 days of therapy over the course of 6 months, while those in the 4% arm missed 50 days. Dr. Epstein attributed this discrepancy to a freak of randomization that can occur in such a small study: 5 of 6 patients in the 2% patidegib group were women, while most in the 4% arm were men. And the men were far less adherent to treatment, possibly because men are less accustomed to applying a product on their face daily, he noted.
In any case, it’s the 2% gel formulation that is moving on to a phase 3, double-blind, randomized trial. The 150-patient U.S. and European study, scheduled to start this summer, will have as its primary endpoint the rate of new BCCs over the course of 1 year. The Food and Drug Administration has granted topical patidegib Breakthrough Drug and Orphan Drug status.
Dr. Epstein said that, in the phase 2 study, BCC shrinkage occurred only in patients whose hedgehog pathway activity decreased after 6 weeks of topical therapy as evidenced by a reduction in the GLI1 mRNA biomarker. Of note, circulating blood levels of patidegib in study participants were more than 500-fold lower than when the drug is given orally. And of greatest importance, rates of the hallmark side effects of oral hedgehog inhibitor therapy that cause so many patients to discontinue therapy – muscle cramps, taste loss, and hair loss – were no different in patients on patidegib gel than in those on placebo.
“In the randomized trial of vismodegib [Erivedge], half of patients stopped taking it within 1 year despite good results. And indeed, when they stopped taking the drug, the basal cell carcinomas returned,” the dermatologist noted.
Dr. Epstein is an employee of PellePharm, which is developing patidegib. Dermatologists with patients with Gorlin syndrome who are interested in participating in the phase 3 trial can contact him at eepstein@pellepharm.com.
CHICAGO – in a phase 2 study, and did so without causing the problematic adverse events that prompt many Gorlin patients to discontinue systemic hedgehog inhibitor drugs, Ervin Epstein Jr., MD, said at the annual meeting of the American College of Mohs Surgery.
He characterized patidegib, a small-molecule cyclopamine derivative, as “a Goldilocks drug, a topical hedgehog inhibitor with percutaneous absorption that’s just right: sufficient to have anti-hedgehog and anti–basal cell carcinoma efficacy, but not enough to cause systemic exposure or systemic adverse events.”
A complete response – tumor clinical disappearance – occurred in 25% of the BCCs in the two active treatment arms. In contrast, none of the BCCs in the control group cleared. Patients on patidegib developed one or more new surgically eligible BCCs after study week 2 at a rate of 0.4 tumors per patient, markedly less than the rate of 1.4 tumors per patient in controls.
“We think that prevention is really the place to go with this drug,” said Dr. Epstein, cofounder and chief medical officer at PellePharm, the company based in Menlo Park, Calif., that is developing patidegib.
Indeed, he envisions patidegib gel as lifetime therapy for Gorlin patients.
Tumor shrinkage was significantly greater with 2% patidegib than with the 4% concentration. But so was treatment adherence: Patients in the 2% patidegib arm missed on average just 2 days of therapy over the course of 6 months, while those in the 4% arm missed 50 days. Dr. Epstein attributed this discrepancy to a freak of randomization that can occur in such a small study: 5 of 6 patients in the 2% patidegib group were women, while most in the 4% arm were men. And the men were far less adherent to treatment, possibly because men are less accustomed to applying a product on their face daily, he noted.
In any case, it’s the 2% gel formulation that is moving on to a phase 3, double-blind, randomized trial. The 150-patient U.S. and European study, scheduled to start this summer, will have as its primary endpoint the rate of new BCCs over the course of 1 year. The Food and Drug Administration has granted topical patidegib Breakthrough Drug and Orphan Drug status.
Dr. Epstein said that, in the phase 2 study, BCC shrinkage occurred only in patients whose hedgehog pathway activity decreased after 6 weeks of topical therapy as evidenced by a reduction in the GLI1 mRNA biomarker. Of note, circulating blood levels of patidegib in study participants were more than 500-fold lower than when the drug is given orally. And of greatest importance, rates of the hallmark side effects of oral hedgehog inhibitor therapy that cause so many patients to discontinue therapy – muscle cramps, taste loss, and hair loss – were no different in patients on patidegib gel than in those on placebo.
“In the randomized trial of vismodegib [Erivedge], half of patients stopped taking it within 1 year despite good results. And indeed, when they stopped taking the drug, the basal cell carcinomas returned,” the dermatologist noted.
Dr. Epstein is an employee of PellePharm, which is developing patidegib. Dermatologists with patients with Gorlin syndrome who are interested in participating in the phase 3 trial can contact him at eepstein@pellepharm.com.
CHICAGO – in a phase 2 study, and did so without causing the problematic adverse events that prompt many Gorlin patients to discontinue systemic hedgehog inhibitor drugs, Ervin Epstein Jr., MD, said at the annual meeting of the American College of Mohs Surgery.
He characterized patidegib, a small-molecule cyclopamine derivative, as “a Goldilocks drug, a topical hedgehog inhibitor with percutaneous absorption that’s just right: sufficient to have anti-hedgehog and anti–basal cell carcinoma efficacy, but not enough to cause systemic exposure or systemic adverse events.”
A complete response – tumor clinical disappearance – occurred in 25% of the BCCs in the two active treatment arms. In contrast, none of the BCCs in the control group cleared. Patients on patidegib developed one or more new surgically eligible BCCs after study week 2 at a rate of 0.4 tumors per patient, markedly less than the rate of 1.4 tumors per patient in controls.
“We think that prevention is really the place to go with this drug,” said Dr. Epstein, cofounder and chief medical officer at PellePharm, the company based in Menlo Park, Calif., that is developing patidegib.
Indeed, he envisions patidegib gel as lifetime therapy for Gorlin patients.
Tumor shrinkage was significantly greater with 2% patidegib than with the 4% concentration. But so was treatment adherence: Patients in the 2% patidegib arm missed on average just 2 days of therapy over the course of 6 months, while those in the 4% arm missed 50 days. Dr. Epstein attributed this discrepancy to a freak of randomization that can occur in such a small study: 5 of 6 patients in the 2% patidegib group were women, while most in the 4% arm were men. And the men were far less adherent to treatment, possibly because men are less accustomed to applying a product on their face daily, he noted.
In any case, it’s the 2% gel formulation that is moving on to a phase 3, double-blind, randomized trial. The 150-patient U.S. and European study, scheduled to start this summer, will have as its primary endpoint the rate of new BCCs over the course of 1 year. The Food and Drug Administration has granted topical patidegib Breakthrough Drug and Orphan Drug status.
Dr. Epstein said that, in the phase 2 study, BCC shrinkage occurred only in patients whose hedgehog pathway activity decreased after 6 weeks of topical therapy as evidenced by a reduction in the GLI1 mRNA biomarker. Of note, circulating blood levels of patidegib in study participants were more than 500-fold lower than when the drug is given orally. And of greatest importance, rates of the hallmark side effects of oral hedgehog inhibitor therapy that cause so many patients to discontinue therapy – muscle cramps, taste loss, and hair loss – were no different in patients on patidegib gel than in those on placebo.
“In the randomized trial of vismodegib [Erivedge], half of patients stopped taking it within 1 year despite good results. And indeed, when they stopped taking the drug, the basal cell carcinomas returned,” the dermatologist noted.
Dr. Epstein is an employee of PellePharm, which is developing patidegib. Dermatologists with patients with Gorlin syndrome who are interested in participating in the phase 3 trial can contact him at eepstein@pellepharm.com.
REPORTING FROM THE ACMS ANNUAL MEETING
Vestibular/oculomotor component of concussion warrants more attention
NEW ORLEANS – Vestibular and oculomotor impairment is increasingly recognized as a common, underappreciated, and yet treatable aspect of sports concussions, Gary W. Dorshimer, MD, said at the annual meeting of the American College of Physicians.
A major advance in the diagnosis and treatment of this form of impairment has been achieved by researchers at the University of Pittsburgh Medical Center sports medicine concussion program.
“The Pitt group has come up with a nice exam to assess this part of the concussion injury, which doesn’t affect your memory, it doesn’t affect your cognition, it affects what I’ve found to be the thing that takes the longest to get better: the oculomotor/vestibular mechanism,” explained Dr. Dorshimer, chief of general internal medicine at Penn Medicine, Philadelphia, and team physician for the Philadelphia Flyers professional ice hockey team.
The exam, which the Pitt group has described in full detail (Am J Sports Med. 2014;42(10):2479-86), is known as the Vestibular/Ocular Motor Screening assessment, or VOMS. The tool has filled an unmet need in sports medicine, he said. It takes only a few minutes for a physician to perform. The rating scale assesses visual motion sensitivity, smooth eye pursuits, horizontal and vertical saccades, the vestibular ocular reflex, and convergence. Positive findings warrant specialized referral for targeted rehabilitation using visual-ocular and vestibular therapies.
The symptoms of sports concussion–related oculomotor/vestibular impairment may include nausea, vertigo, dizziness, blurred or double vision, difficulty tracking a moving target, and discomfort in busy environments. These symptoms often translate to difficulty reading and academic problems, which historically often were misinterpreted as cognitive impairments.
It’s estimated that oculomotor/vestibular impairment occurs in roughly 60% of sports concussions. These vestibular and/or vision symptoms are associated with protracted recovery. And preliminary evidence demonstrates that targeted physical therapies are effective in speeding recovery.
“It’s so important to be able to find this [impairment] because it’s something you can do something about. We find that when these things are off and people work on them, they get better. That’s why so many people in the field are now saying that if a patient works hard, does the rehabilitation, the majority of them are going to get better. And they won’t get better unless they press forward,” the internist said.
The VOMS screen is simple to perform. It entails tasks such as convergence testing, in which the physician moves a finger or pen steadily closer to the patient’s face; if the patient reports that the single object has turned into two at a distance of more than 6 cm, that’s a positive result indicative of convergence insufficiency.
In another task, the physician hold his two index fingers apart and has the patients move their eyes from finger to finger while holding their heads still.
“I’m not that interested in whether they’re catching the tips of fingers, I’m interested in if they can go fast, and can they go faster if I challenge them, or do they stop doing it? When people with ocular vestibular dysfunction start doing this task, they’re going to slow down. They can’t keep it up because it’s so unpleasant. It really bothers them a lot,” Dr. Dorshimer observed.
In his experience, another key element in a smooth and successful recovery from sports concussions, in addition to getting skilled help for vestibular/oculomotor impairment, if present, is to encourage a positive attitude.
“If you think you’re going to get CTE [chronic traumatic encephalopathy] when you get older because you got waffled a bit in sport, that’s just such a negative attitude. I mean, you can’t lie to them: We don’t know. But I take care of a ton of retired athletes who don’t have CTE. Maybe they’re going to have some tangles in their brains, but they don’t have it clinically. So you want them to keep a positive attitude,” he emphasized.
“CTE was around when your parents and grandparents were jocks. They went out on the playground and pummeled each other every day after school. There are probably all kinds of factors involved in CTE: the number of concussions, hereditary factors, alcohol, drugs. No one really knows yet,” he said.
Dr. Dorshimer reported having no financial conflicts regarding his presentation on the athlete as patient.
NEW ORLEANS – Vestibular and oculomotor impairment is increasingly recognized as a common, underappreciated, and yet treatable aspect of sports concussions, Gary W. Dorshimer, MD, said at the annual meeting of the American College of Physicians.
A major advance in the diagnosis and treatment of this form of impairment has been achieved by researchers at the University of Pittsburgh Medical Center sports medicine concussion program.
“The Pitt group has come up with a nice exam to assess this part of the concussion injury, which doesn’t affect your memory, it doesn’t affect your cognition, it affects what I’ve found to be the thing that takes the longest to get better: the oculomotor/vestibular mechanism,” explained Dr. Dorshimer, chief of general internal medicine at Penn Medicine, Philadelphia, and team physician for the Philadelphia Flyers professional ice hockey team.
The exam, which the Pitt group has described in full detail (Am J Sports Med. 2014;42(10):2479-86), is known as the Vestibular/Ocular Motor Screening assessment, or VOMS. The tool has filled an unmet need in sports medicine, he said. It takes only a few minutes for a physician to perform. The rating scale assesses visual motion sensitivity, smooth eye pursuits, horizontal and vertical saccades, the vestibular ocular reflex, and convergence. Positive findings warrant specialized referral for targeted rehabilitation using visual-ocular and vestibular therapies.
The symptoms of sports concussion–related oculomotor/vestibular impairment may include nausea, vertigo, dizziness, blurred or double vision, difficulty tracking a moving target, and discomfort in busy environments. These symptoms often translate to difficulty reading and academic problems, which historically often were misinterpreted as cognitive impairments.
It’s estimated that oculomotor/vestibular impairment occurs in roughly 60% of sports concussions. These vestibular and/or vision symptoms are associated with protracted recovery. And preliminary evidence demonstrates that targeted physical therapies are effective in speeding recovery.
“It’s so important to be able to find this [impairment] because it’s something you can do something about. We find that when these things are off and people work on them, they get better. That’s why so many people in the field are now saying that if a patient works hard, does the rehabilitation, the majority of them are going to get better. And they won’t get better unless they press forward,” the internist said.
The VOMS screen is simple to perform. It entails tasks such as convergence testing, in which the physician moves a finger or pen steadily closer to the patient’s face; if the patient reports that the single object has turned into two at a distance of more than 6 cm, that’s a positive result indicative of convergence insufficiency.
In another task, the physician hold his two index fingers apart and has the patients move their eyes from finger to finger while holding their heads still.
“I’m not that interested in whether they’re catching the tips of fingers, I’m interested in if they can go fast, and can they go faster if I challenge them, or do they stop doing it? When people with ocular vestibular dysfunction start doing this task, they’re going to slow down. They can’t keep it up because it’s so unpleasant. It really bothers them a lot,” Dr. Dorshimer observed.
In his experience, another key element in a smooth and successful recovery from sports concussions, in addition to getting skilled help for vestibular/oculomotor impairment, if present, is to encourage a positive attitude.
“If you think you’re going to get CTE [chronic traumatic encephalopathy] when you get older because you got waffled a bit in sport, that’s just such a negative attitude. I mean, you can’t lie to them: We don’t know. But I take care of a ton of retired athletes who don’t have CTE. Maybe they’re going to have some tangles in their brains, but they don’t have it clinically. So you want them to keep a positive attitude,” he emphasized.
“CTE was around when your parents and grandparents were jocks. They went out on the playground and pummeled each other every day after school. There are probably all kinds of factors involved in CTE: the number of concussions, hereditary factors, alcohol, drugs. No one really knows yet,” he said.
Dr. Dorshimer reported having no financial conflicts regarding his presentation on the athlete as patient.
NEW ORLEANS – Vestibular and oculomotor impairment is increasingly recognized as a common, underappreciated, and yet treatable aspect of sports concussions, Gary W. Dorshimer, MD, said at the annual meeting of the American College of Physicians.
A major advance in the diagnosis and treatment of this form of impairment has been achieved by researchers at the University of Pittsburgh Medical Center sports medicine concussion program.
“The Pitt group has come up with a nice exam to assess this part of the concussion injury, which doesn’t affect your memory, it doesn’t affect your cognition, it affects what I’ve found to be the thing that takes the longest to get better: the oculomotor/vestibular mechanism,” explained Dr. Dorshimer, chief of general internal medicine at Penn Medicine, Philadelphia, and team physician for the Philadelphia Flyers professional ice hockey team.
The exam, which the Pitt group has described in full detail (Am J Sports Med. 2014;42(10):2479-86), is known as the Vestibular/Ocular Motor Screening assessment, or VOMS. The tool has filled an unmet need in sports medicine, he said. It takes only a few minutes for a physician to perform. The rating scale assesses visual motion sensitivity, smooth eye pursuits, horizontal and vertical saccades, the vestibular ocular reflex, and convergence. Positive findings warrant specialized referral for targeted rehabilitation using visual-ocular and vestibular therapies.
The symptoms of sports concussion–related oculomotor/vestibular impairment may include nausea, vertigo, dizziness, blurred or double vision, difficulty tracking a moving target, and discomfort in busy environments. These symptoms often translate to difficulty reading and academic problems, which historically often were misinterpreted as cognitive impairments.
It’s estimated that oculomotor/vestibular impairment occurs in roughly 60% of sports concussions. These vestibular and/or vision symptoms are associated with protracted recovery. And preliminary evidence demonstrates that targeted physical therapies are effective in speeding recovery.
“It’s so important to be able to find this [impairment] because it’s something you can do something about. We find that when these things are off and people work on them, they get better. That’s why so many people in the field are now saying that if a patient works hard, does the rehabilitation, the majority of them are going to get better. And they won’t get better unless they press forward,” the internist said.
The VOMS screen is simple to perform. It entails tasks such as convergence testing, in which the physician moves a finger or pen steadily closer to the patient’s face; if the patient reports that the single object has turned into two at a distance of more than 6 cm, that’s a positive result indicative of convergence insufficiency.
In another task, the physician hold his two index fingers apart and has the patients move their eyes from finger to finger while holding their heads still.
“I’m not that interested in whether they’re catching the tips of fingers, I’m interested in if they can go fast, and can they go faster if I challenge them, or do they stop doing it? When people with ocular vestibular dysfunction start doing this task, they’re going to slow down. They can’t keep it up because it’s so unpleasant. It really bothers them a lot,” Dr. Dorshimer observed.
In his experience, another key element in a smooth and successful recovery from sports concussions, in addition to getting skilled help for vestibular/oculomotor impairment, if present, is to encourage a positive attitude.
“If you think you’re going to get CTE [chronic traumatic encephalopathy] when you get older because you got waffled a bit in sport, that’s just such a negative attitude. I mean, you can’t lie to them: We don’t know. But I take care of a ton of retired athletes who don’t have CTE. Maybe they’re going to have some tangles in their brains, but they don’t have it clinically. So you want them to keep a positive attitude,” he emphasized.
“CTE was around when your parents and grandparents were jocks. They went out on the playground and pummeled each other every day after school. There are probably all kinds of factors involved in CTE: the number of concussions, hereditary factors, alcohol, drugs. No one really knows yet,” he said.
Dr. Dorshimer reported having no financial conflicts regarding his presentation on the athlete as patient.
REPORTING FROM ACP INTERNAL MEDICINE
To detect subclinical AF, insertable monitor is unequaled
ORLANDO – with other intermittent ambulatory monitoring strategies, in a secondary analysis from the REVEAL AF study.
“If you really want to look for atrial fibrillation because your concern is that the patient has a high-risk profile, and if you saw it you would anticoagulate it and maybe prophylactically use rate control, nothing beats the implanted monitor,” James A. Reiffel, MD, said at the annual meeting of the American College of Cardiology.
As previously reported (JAMA Cardiol. 2017 Oct 1;2[10]:1120-7), the primary outcome – an AF episode lasting for at least 6 minutes – occurred during the first 18 months of the study in 29% of participants. By 30 months, it was 40%. At ACC 2018, Dr. Reiffel presented a new analysis looking at how the insertable cardiac monitor (ICM) would have stacked up against other device-based strategies aimed at detecting silent AF, including a 30-day implantable memory loop, daily transtelephonic ECG monitoring, and one-time or periodic 24- or 48-hour Holter monitoring.
To accomplish this, he and his coinvestigators conducted modeling studies harnessing the REVEAL AF continuous monitoring data. They looked at how many of the real-world patients found to have AF in the study would have been identified had they instead undergone a one-time recording period lasting 1, 2, 7, 14, or 30 days beginning at the time they would have received their ICM. They also looked at the yield of repeated monitoring strategies, including monthly or quarterly 24- or 48-hour Holter monitoring sessions. They repeated the various simulated monitoring strategies 10,000 times each in order to beef up the sample size and stability of the results.
It was no contest, according to Dr. Reiffel, professor of clinical medicine at Columbia University in New York.
That’s because the median time to AF detection in REVEAL AF was 123 days. Thus, any monitoring strategy of 30 days duration or less was doomed to be of comparatively low yield. Indeed, the 12-month AF incidence rate as detected by ICM in REVEAL AF was 27.1%, compared with 1.1%-13.5% for the various modeled monitoring strategies.
Among patients who met the primary endpoint in REVEAL AF, 10.2% had one or more AF episodes lasting 24 hours or more. So a significant proportion of the asymptomatic episodes of AF were not brief.
The take-home lesson of this analysis is straightforward, he said. “While the incidence of screen-detected atrial fibrillation is dependent upon the population screened, it is also strongly dependent upon the duration and intensity of monitoring.”
Session cochair Jeanne E. Poole, MD, observed that while the new REVEAL AF analysis is informative, it leaves unanswered the big questions regarding the clinical importance of these silent episodes of subclinical device-detected AF. That is, are these episodes associated with significantly increased stroke risk, and if so are they just another nonmodifiable risk marker, or are they a risk factor that can be dampened via oral anticoagulation, like symptomatic AF? said Dr. Poole, professor of medicine and director of the clinical cardiac electrophysiology program at the University of Washington, Seattle.
“My own belief is that they are both a risk marker and a risk factor that contributes to stroke,” Dr. Reiffel replied.
He noted that there are two major ongoing clinical trials evaluating the impact of oral anticoagulation in patients with ICM-detected AF. The 3,400-patient German multicenter Non–vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes (NOAH–AFNET 6 ) trial is testing whether oral anticoagulation with edoxaban (Savaysa) is superior to aspirin or no antithrombotic therapy for prevention of stroke or cardiovascular death. And the 4,000-patient Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESIA) trial is randomizing patients to apixaban (Eliquis) or aspirin.
“We’ll know within the next 3-4 years whether patients with high-risk profiles for atrial fibrillation but no clinically manifest atrial fibrillation should in fact be detected and should in fact be anticoagulated if atrial fibrillation is detected. Putting on my ‘Carnac The Magnificent’ hat [made famous by Johnny Carson on the ‘Tonight Show’], I predict the answer to both of those questions is likely to be yes,” the cardiologist added.
He noted that the Medtronic ICM, which is one-third the size of a AAA battery, is implanted via a small incision, which is then covered by a adhesive bandage.
“There’s no major surgical technique involved in putting [int ICM] in,” he said.
The REVEAL AF study was sponsored by Medtronic. Dr. Reiffel reported serving as a consultant to the company.
SOURCE: Reiffel JA et al. ACC 2018, Abstract 900-08.
ORLANDO – with other intermittent ambulatory monitoring strategies, in a secondary analysis from the REVEAL AF study.
“If you really want to look for atrial fibrillation because your concern is that the patient has a high-risk profile, and if you saw it you would anticoagulate it and maybe prophylactically use rate control, nothing beats the implanted monitor,” James A. Reiffel, MD, said at the annual meeting of the American College of Cardiology.
As previously reported (JAMA Cardiol. 2017 Oct 1;2[10]:1120-7), the primary outcome – an AF episode lasting for at least 6 minutes – occurred during the first 18 months of the study in 29% of participants. By 30 months, it was 40%. At ACC 2018, Dr. Reiffel presented a new analysis looking at how the insertable cardiac monitor (ICM) would have stacked up against other device-based strategies aimed at detecting silent AF, including a 30-day implantable memory loop, daily transtelephonic ECG monitoring, and one-time or periodic 24- or 48-hour Holter monitoring.
To accomplish this, he and his coinvestigators conducted modeling studies harnessing the REVEAL AF continuous monitoring data. They looked at how many of the real-world patients found to have AF in the study would have been identified had they instead undergone a one-time recording period lasting 1, 2, 7, 14, or 30 days beginning at the time they would have received their ICM. They also looked at the yield of repeated monitoring strategies, including monthly or quarterly 24- or 48-hour Holter monitoring sessions. They repeated the various simulated monitoring strategies 10,000 times each in order to beef up the sample size and stability of the results.
It was no contest, according to Dr. Reiffel, professor of clinical medicine at Columbia University in New York.
That’s because the median time to AF detection in REVEAL AF was 123 days. Thus, any monitoring strategy of 30 days duration or less was doomed to be of comparatively low yield. Indeed, the 12-month AF incidence rate as detected by ICM in REVEAL AF was 27.1%, compared with 1.1%-13.5% for the various modeled monitoring strategies.
Among patients who met the primary endpoint in REVEAL AF, 10.2% had one or more AF episodes lasting 24 hours or more. So a significant proportion of the asymptomatic episodes of AF were not brief.
The take-home lesson of this analysis is straightforward, he said. “While the incidence of screen-detected atrial fibrillation is dependent upon the population screened, it is also strongly dependent upon the duration and intensity of monitoring.”
Session cochair Jeanne E. Poole, MD, observed that while the new REVEAL AF analysis is informative, it leaves unanswered the big questions regarding the clinical importance of these silent episodes of subclinical device-detected AF. That is, are these episodes associated with significantly increased stroke risk, and if so are they just another nonmodifiable risk marker, or are they a risk factor that can be dampened via oral anticoagulation, like symptomatic AF? said Dr. Poole, professor of medicine and director of the clinical cardiac electrophysiology program at the University of Washington, Seattle.
“My own belief is that they are both a risk marker and a risk factor that contributes to stroke,” Dr. Reiffel replied.
He noted that there are two major ongoing clinical trials evaluating the impact of oral anticoagulation in patients with ICM-detected AF. The 3,400-patient German multicenter Non–vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes (NOAH–AFNET 6 ) trial is testing whether oral anticoagulation with edoxaban (Savaysa) is superior to aspirin or no antithrombotic therapy for prevention of stroke or cardiovascular death. And the 4,000-patient Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESIA) trial is randomizing patients to apixaban (Eliquis) or aspirin.
“We’ll know within the next 3-4 years whether patients with high-risk profiles for atrial fibrillation but no clinically manifest atrial fibrillation should in fact be detected and should in fact be anticoagulated if atrial fibrillation is detected. Putting on my ‘Carnac The Magnificent’ hat [made famous by Johnny Carson on the ‘Tonight Show’], I predict the answer to both of those questions is likely to be yes,” the cardiologist added.
He noted that the Medtronic ICM, which is one-third the size of a AAA battery, is implanted via a small incision, which is then covered by a adhesive bandage.
“There’s no major surgical technique involved in putting [int ICM] in,” he said.
The REVEAL AF study was sponsored by Medtronic. Dr. Reiffel reported serving as a consultant to the company.
SOURCE: Reiffel JA et al. ACC 2018, Abstract 900-08.
ORLANDO – with other intermittent ambulatory monitoring strategies, in a secondary analysis from the REVEAL AF study.
“If you really want to look for atrial fibrillation because your concern is that the patient has a high-risk profile, and if you saw it you would anticoagulate it and maybe prophylactically use rate control, nothing beats the implanted monitor,” James A. Reiffel, MD, said at the annual meeting of the American College of Cardiology.
As previously reported (JAMA Cardiol. 2017 Oct 1;2[10]:1120-7), the primary outcome – an AF episode lasting for at least 6 minutes – occurred during the first 18 months of the study in 29% of participants. By 30 months, it was 40%. At ACC 2018, Dr. Reiffel presented a new analysis looking at how the insertable cardiac monitor (ICM) would have stacked up against other device-based strategies aimed at detecting silent AF, including a 30-day implantable memory loop, daily transtelephonic ECG monitoring, and one-time or periodic 24- or 48-hour Holter monitoring.
To accomplish this, he and his coinvestigators conducted modeling studies harnessing the REVEAL AF continuous monitoring data. They looked at how many of the real-world patients found to have AF in the study would have been identified had they instead undergone a one-time recording period lasting 1, 2, 7, 14, or 30 days beginning at the time they would have received their ICM. They also looked at the yield of repeated monitoring strategies, including monthly or quarterly 24- or 48-hour Holter monitoring sessions. They repeated the various simulated monitoring strategies 10,000 times each in order to beef up the sample size and stability of the results.
It was no contest, according to Dr. Reiffel, professor of clinical medicine at Columbia University in New York.
That’s because the median time to AF detection in REVEAL AF was 123 days. Thus, any monitoring strategy of 30 days duration or less was doomed to be of comparatively low yield. Indeed, the 12-month AF incidence rate as detected by ICM in REVEAL AF was 27.1%, compared with 1.1%-13.5% for the various modeled monitoring strategies.
Among patients who met the primary endpoint in REVEAL AF, 10.2% had one or more AF episodes lasting 24 hours or more. So a significant proportion of the asymptomatic episodes of AF were not brief.
The take-home lesson of this analysis is straightforward, he said. “While the incidence of screen-detected atrial fibrillation is dependent upon the population screened, it is also strongly dependent upon the duration and intensity of monitoring.”
Session cochair Jeanne E. Poole, MD, observed that while the new REVEAL AF analysis is informative, it leaves unanswered the big questions regarding the clinical importance of these silent episodes of subclinical device-detected AF. That is, are these episodes associated with significantly increased stroke risk, and if so are they just another nonmodifiable risk marker, or are they a risk factor that can be dampened via oral anticoagulation, like symptomatic AF? said Dr. Poole, professor of medicine and director of the clinical cardiac electrophysiology program at the University of Washington, Seattle.
“My own belief is that they are both a risk marker and a risk factor that contributes to stroke,” Dr. Reiffel replied.
He noted that there are two major ongoing clinical trials evaluating the impact of oral anticoagulation in patients with ICM-detected AF. The 3,400-patient German multicenter Non–vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes (NOAH–AFNET 6 ) trial is testing whether oral anticoagulation with edoxaban (Savaysa) is superior to aspirin or no antithrombotic therapy for prevention of stroke or cardiovascular death. And the 4,000-patient Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation (ARTESIA) trial is randomizing patients to apixaban (Eliquis) or aspirin.
“We’ll know within the next 3-4 years whether patients with high-risk profiles for atrial fibrillation but no clinically manifest atrial fibrillation should in fact be detected and should in fact be anticoagulated if atrial fibrillation is detected. Putting on my ‘Carnac The Magnificent’ hat [made famous by Johnny Carson on the ‘Tonight Show’], I predict the answer to both of those questions is likely to be yes,” the cardiologist added.
He noted that the Medtronic ICM, which is one-third the size of a AAA battery, is implanted via a small incision, which is then covered by a adhesive bandage.
“There’s no major surgical technique involved in putting [int ICM] in,” he said.
The REVEAL AF study was sponsored by Medtronic. Dr. Reiffel reported serving as a consultant to the company.
SOURCE: Reiffel JA et al. ACC 2018, Abstract 900-08.
REPORTING FROM ACC 2018
Key clinical point: Most patients at high risk for previously unidentified atrial fibrillation whose arrhythmia is detected by means of an insertable continuous ECG monitor would go unidentified by any other detection strategy.
Major finding: The median time to insertable cardiac monitor–based detection of a first episode of silent AF of at least 6 minutes length was 123 days.
Study details: This was a multicenter, prospective, single-arm study of 385 patients at high risk for AF who received an insertable cardiac monitor and were followed for 30 months.
Disclosures: The REVEAL AF study was sponsored by Medtronic. The presenter reported serving as a consultant to the company.
Source: Reiffel JA et al. ACC 2018, Abstract 900-08.