Bruce Jancin

Oral difelikefalin significantly reduced the intense itching associated with stage 3-5 chronic kidney disease, with or without hemodialysis, in a first-of-its-kind randomized clinical trial, Gil Yosipovitch, MD, said at the virtual annual meeting of the American Academy of Dermatology.

“Difelikefalin at 1.0 mg was associated with clinically meaningful improvements in pruritus. The improvement in itch was significant by week 2. And nearly 40% of patients achieved a complete response, which was more than two-and-one-half times more than with placebo,” noted Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami.

Pruritus associated with chronic kidney disease (CKD) is a common, underrecognized, and distressing condition that causes markedly impaired quality of life. It occurs in patients across all stages of CKD, not just in those on hemodialysis, as is widely but mistakenly believed. And at present there is no approved drug in any country for treatment of CKD-associated itch.

Difelikefalin, a novel selective agonist of peripheral kappa opioid receptors, is designed to have very limited CNS penetration. The drug, which is renally excreted, doesn’t bind to mu or delta opioid receptors. Its antipruritic effect arises from activation of kappa opioid receptors on peripheral sensory neurons and immune cells, the dermatologist explained.

Dr. Yosipovitch presented the results of a phase 2, randomized, double-blind, placebo-controlled, 12-week trial in which 240 patients with severe chronic pruritus and stage 3-5 CKD were assigned to once-daily oral difelikefalin at 0.25 mg, 0.5 mg, or 1.0 mg, or placebo. More than 80% of participants were not on dialysis. Indeed, this was the first-ever clinical trial targeting itch in patients across such a broad spectrum of CKD stages.

The primary study endpoint was change from baseline to week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale. The average baseline score was 7, considered severe pruritus on the 0-10 scale. Patients randomized to difelikefalin at 1.0 mg/day had a mean 4.4-point decrease, a significantly greater improvement than the 3.3-point reduction in placebo-treated controls.

“More than a 4-point decrease is considered a very meaningful itch reduction,” Dr. Yosipovitch noted.

The mean reductions in itch score in patients on 0.25 mg and 0.5 mg/day of difelikefalin were 4.0 and 3.8 points, respectively, which fell short of statistical significance versus placebo.

A key prespecified secondary endpoint was the proportion of subjects with at least a 3-point improvement in itch score over 12 weeks. This was achieved in 72% of patients on the top dose of difelikefalin, compared with 58% of controls, a significant difference. A 4-point or larger decrease in itch score occurred in 65% of patients on 1.0 mg/day of the kappa opioid recent agonist, versus 50% of controls, also a significant difference.

A complete response, defined as an itch score of 0 or 1 at least 80% of the time, was significantly more common in all three active treatment groups than in controls, with rates of 33%, 31.6%, and 38.6% at difelikefalin 0.25, 0.5, and 1.0 mg, compared with 4.4% among those on placebo.

Falls occurred in 1.5% of patients on difelikefalin. “The therapy does seem to increase the risk of dizziness, falls, fatigue, and GI complaints,” according to the investigator.

Still, most of these adverse events were mild or moderate in severity. Only about 1% of participants discontinued treatment for such reasons.

Earlier this year, a positive phase 3 trial of an intravenous formulation of difelikefalin for pruritus was reported in CKD patients on hemodialysis (N Engl J Med. 2020 Jan 16;382[3]:222-32).

In an interview, Dr. Yosipovitch said that this new phase 2 oral dose-finding study wasn’t powered to detect differences in treatment efficacy between the dialysis and nondialysis groups. However, the proportion of patients with at least a 3-point improvement in itch at week 12 was similar in the two groups.

“The oral formulation would of course be more convenient and would be preferred for patients not undergoing hemodialysis,” he said. “I would expect that the IV formulation would be the preferred route of administration for a patient undergoing hemodialysis. An IV formulation would be very convenient for such patients because it’s administered at the dialysis clinic at the end of the hemodialysis session.”

The oral difelikefalin phase 3 program is scheduled to start later in 2020.

CKD-associated itch poses a therapeutic challenge because it has so many contributory factors. These include CKD-induced peripheral neuropathy, functional and structural neuropathic changes in the brain, cutaneous mast cell activation, an imbalance between mu opioid receptor overexpression and kappa opioid receptor downregulation, secondary parathyroidism, and systemic accumulation of aluminum, beta 2 microglobulin, and other dialysis-related substances, the dermatologist observed.

Dr. Yosipovitch reported receiving research grants from a half-dozen pharmaceutical companies. He also serves as a consultant to numerous companies, including Cara Therapeutics, which sponsored the phase 2 trial.

bjancin@mdedge.com

Oral difelikefalin significantly reduced the intense itching associated with stage 3-5 chronic kidney disease, with or without hemodialysis, in a first-of-its-kind randomized clinical trial, Gil Yosipovitch, MD, said at the virtual annual meeting of the American Academy of Dermatology.

“Difelikefalin at 1.0 mg was associated with clinically meaningful improvements in pruritus. The improvement in itch was significant by week 2. And nearly 40% of patients achieved a complete response, which was more than two-and-one-half times more than with placebo,” noted Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami.

Pruritus associated with chronic kidney disease (CKD) is a common, underrecognized, and distressing condition that causes markedly impaired quality of life. It occurs in patients across all stages of CKD, not just in those on hemodialysis, as is widely but mistakenly believed. And at present there is no approved drug in any country for treatment of CKD-associated itch.

Difelikefalin, a novel selective agonist of peripheral kappa opioid receptors, is designed to have very limited CNS penetration. The drug, which is renally excreted, doesn’t bind to mu or delta opioid receptors. Its antipruritic effect arises from activation of kappa opioid receptors on peripheral sensory neurons and immune cells, the dermatologist explained.

Dr. Yosipovitch presented the results of a phase 2, randomized, double-blind, placebo-controlled, 12-week trial in which 240 patients with severe chronic pruritus and stage 3-5 CKD were assigned to once-daily oral difelikefalin at 0.25 mg, 0.5 mg, or 1.0 mg, or placebo. More than 80% of participants were not on dialysis. Indeed, this was the first-ever clinical trial targeting itch in patients across such a broad spectrum of CKD stages.

The primary study endpoint was change from baseline to week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale. The average baseline score was 7, considered severe pruritus on the 0-10 scale. Patients randomized to difelikefalin at 1.0 mg/day had a mean 4.4-point decrease, a significantly greater improvement than the 3.3-point reduction in placebo-treated controls.

“More than a 4-point decrease is considered a very meaningful itch reduction,” Dr. Yosipovitch noted.

The mean reductions in itch score in patients on 0.25 mg and 0.5 mg/day of difelikefalin were 4.0 and 3.8 points, respectively, which fell short of statistical significance versus placebo.

A key prespecified secondary endpoint was the proportion of subjects with at least a 3-point improvement in itch score over 12 weeks. This was achieved in 72% of patients on the top dose of difelikefalin, compared with 58% of controls, a significant difference. A 4-point or larger decrease in itch score occurred in 65% of patients on 1.0 mg/day of the kappa opioid recent agonist, versus 50% of controls, also a significant difference.

A complete response, defined as an itch score of 0 or 1 at least 80% of the time, was significantly more common in all three active treatment groups than in controls, with rates of 33%, 31.6%, and 38.6% at difelikefalin 0.25, 0.5, and 1.0 mg, compared with 4.4% among those on placebo.

Falls occurred in 1.5% of patients on difelikefalin. “The therapy does seem to increase the risk of dizziness, falls, fatigue, and GI complaints,” according to the investigator.

Still, most of these adverse events were mild or moderate in severity. Only about 1% of participants discontinued treatment for such reasons.

Earlier this year, a positive phase 3 trial of an intravenous formulation of difelikefalin for pruritus was reported in CKD patients on hemodialysis (N Engl J Med. 2020 Jan 16;382[3]:222-32).

In an interview, Dr. Yosipovitch said that this new phase 2 oral dose-finding study wasn’t powered to detect differences in treatment efficacy between the dialysis and nondialysis groups. However, the proportion of patients with at least a 3-point improvement in itch at week 12 was similar in the two groups.

“The oral formulation would of course be more convenient and would be preferred for patients not undergoing hemodialysis,” he said. “I would expect that the IV formulation would be the preferred route of administration for a patient undergoing hemodialysis. An IV formulation would be very convenient for such patients because it’s administered at the dialysis clinic at the end of the hemodialysis session.”

The oral difelikefalin phase 3 program is scheduled to start later in 2020.

CKD-associated itch poses a therapeutic challenge because it has so many contributory factors. These include CKD-induced peripheral neuropathy, functional and structural neuropathic changes in the brain, cutaneous mast cell activation, an imbalance between mu opioid receptor overexpression and kappa opioid receptor downregulation, secondary parathyroidism, and systemic accumulation of aluminum, beta 2 microglobulin, and other dialysis-related substances, the dermatologist observed.

Dr. Yosipovitch reported receiving research grants from a half-dozen pharmaceutical companies. He also serves as a consultant to numerous companies, including Cara Therapeutics, which sponsored the phase 2 trial.

bjancin@mdedge.com

Oral difelikefalin significantly reduced the intense itching associated with stage 3-5 chronic kidney disease, with or without hemodialysis, in a first-of-its-kind randomized clinical trial, Gil Yosipovitch, MD, said at the virtual annual meeting of the American Academy of Dermatology.

“Difelikefalin at 1.0 mg was associated with clinically meaningful improvements in pruritus. The improvement in itch was significant by week 2. And nearly 40% of patients achieved a complete response, which was more than two-and-one-half times more than with placebo,” noted Dr. Yosipovitch, professor of dermatology and director of the Miami Itch Center at the University of Miami.

Pruritus associated with chronic kidney disease (CKD) is a common, underrecognized, and distressing condition that causes markedly impaired quality of life. It occurs in patients across all stages of CKD, not just in those on hemodialysis, as is widely but mistakenly believed. And at present there is no approved drug in any country for treatment of CKD-associated itch.

Difelikefalin, a novel selective agonist of peripheral kappa opioid receptors, is designed to have very limited CNS penetration. The drug, which is renally excreted, doesn’t bind to mu or delta opioid receptors. Its antipruritic effect arises from activation of kappa opioid receptors on peripheral sensory neurons and immune cells, the dermatologist explained.

Dr. Yosipovitch presented the results of a phase 2, randomized, double-blind, placebo-controlled, 12-week trial in which 240 patients with severe chronic pruritus and stage 3-5 CKD were assigned to once-daily oral difelikefalin at 0.25 mg, 0.5 mg, or 1.0 mg, or placebo. More than 80% of participants were not on dialysis. Indeed, this was the first-ever clinical trial targeting itch in patients across such a broad spectrum of CKD stages.

The primary study endpoint was change from baseline to week 12 in the weekly mean score on the 24-hour Worst Itching Intensity Numerical Rating Scale. The average baseline score was 7, considered severe pruritus on the 0-10 scale. Patients randomized to difelikefalin at 1.0 mg/day had a mean 4.4-point decrease, a significantly greater improvement than the 3.3-point reduction in placebo-treated controls.

“More than a 4-point decrease is considered a very meaningful itch reduction,” Dr. Yosipovitch noted.

The mean reductions in itch score in patients on 0.25 mg and 0.5 mg/day of difelikefalin were 4.0 and 3.8 points, respectively, which fell short of statistical significance versus placebo.

A key prespecified secondary endpoint was the proportion of subjects with at least a 3-point improvement in itch score over 12 weeks. This was achieved in 72% of patients on the top dose of difelikefalin, compared with 58% of controls, a significant difference. A 4-point or larger decrease in itch score occurred in 65% of patients on 1.0 mg/day of the kappa opioid recent agonist, versus 50% of controls, also a significant difference.

A complete response, defined as an itch score of 0 or 1 at least 80% of the time, was significantly more common in all three active treatment groups than in controls, with rates of 33%, 31.6%, and 38.6% at difelikefalin 0.25, 0.5, and 1.0 mg, compared with 4.4% among those on placebo.

Falls occurred in 1.5% of patients on difelikefalin. “The therapy does seem to increase the risk of dizziness, falls, fatigue, and GI complaints,” according to the investigator.

Still, most of these adverse events were mild or moderate in severity. Only about 1% of participants discontinued treatment for such reasons.

Earlier this year, a positive phase 3 trial of an intravenous formulation of difelikefalin for pruritus was reported in CKD patients on hemodialysis (N Engl J Med. 2020 Jan 16;382[3]:222-32).

In an interview, Dr. Yosipovitch said that this new phase 2 oral dose-finding study wasn’t powered to detect differences in treatment efficacy between the dialysis and nondialysis groups. However, the proportion of patients with at least a 3-point improvement in itch at week 12 was similar in the two groups.

“The oral formulation would of course be more convenient and would be preferred for patients not undergoing hemodialysis,” he said. “I would expect that the IV formulation would be the preferred route of administration for a patient undergoing hemodialysis. An IV formulation would be very convenient for such patients because it’s administered at the dialysis clinic at the end of the hemodialysis session.”

The oral difelikefalin phase 3 program is scheduled to start later in 2020.

CKD-associated itch poses a therapeutic challenge because it has so many contributory factors. These include CKD-induced peripheral neuropathy, functional and structural neuropathic changes in the brain, cutaneous mast cell activation, an imbalance between mu opioid receptor overexpression and kappa opioid receptor downregulation, secondary parathyroidism, and systemic accumulation of aluminum, beta 2 microglobulin, and other dialysis-related substances, the dermatologist observed.

Dr. Yosipovitch reported receiving research grants from a half-dozen pharmaceutical companies. He also serves as a consultant to numerous companies, including Cara Therapeutics, which sponsored the phase 2 trial.

bjancin@mdedge.com

The care transition period between inpatient psychiatric hospitalization and initiation of outpatient mental health services is a time of extraordinarily heightened suicide risk that has been woefully neglected, according to speakers from the National Action Alliance for Suicide Prevention at the virtual annual meeting of the American Association of Suicidology.

This transition period traditionally has been a time when nobody really takes responsibility for patient care. In an effort to close this potentially deadly gap in services, the alliance recently has issued a report entitled, “Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care.” The recommendations focus on specific, innovative, evidence-based strategies that health care systems can use to prevent patients from falling through the cracks in care, mainly by implementing protocols aimed at fostering interorganizational teamwork between inpatient and outpatient behavioral health services.

“I believe that improving care transitions in the United States is the area where we can likely save the most lives. It’s within our grasp if we can just do this better,” declared Richard McKeon, PhD, MPH, chief of the Suicide Prevention Branch at the Center for Mental Health Services within SAMHSA, the Substance Abuse and Mental Health Services Administration.

He cited a recent meta-analysis that concluded that the risk of suicide during the first week post discharge after psychiatric hospitalization is a staggering 300 times greater than in the general population, while in the first month, the risk is increased 200-fold. The meta-analysis included 29 studies encompassing 3,551 suicides during the first month and 24 studies reporting 1,928 suicides during the first week post discharge (BMJ Open. 2019 Mar 23;9[3]:e023883. doi: 10.1136/bmjopen-2018-023883).

Everyone in the mental health field as well as patients and their families should know those statistics, but they don’t.

“I think it’s natural for people to think someone who’s been discharged from an inpatient unit or the emergency department is not at risk, when in reality it’s still a high-risk time. Suicide risk is not like a light switch that you can just switch off,” the clinical psychologist observed.

He cited other harrowing statistics that underscore the vast problem of poor care transitions. Nationally, fully one-third of patients don’t complete a single outpatient visit within the first 30 days after discharge from inpatient behavioral health care. And one in seven people who die by suicide have had contact with inpatient mental health services in the year before they died.

“That doesn’t mean that inpatient care did not do everything that they could do. What it does reflect is the need to make sure that there’s follow-up care after inpatient discharge. Too often, people don’t get the follow-up care that they need. And the research literature is clear that intervention can save lives,” Dr. McKeon said.

Panelist Becky Stoll, LCSW, vice president for crisis and disaster management at Centerstone Health in Nashville, Tenn., noted, “We see a lot of no-shows on the outpatient side, because nobody ever asked the patients if they can actually get to the outpatient appointment that’s been made.

“We have got to figure out this care transition and do better. The road to mental health is paved with Swiss cheese. There are so many holes to fall into, even if you know how to navigate the system – and most of the people we’re serving don’t know how,” observed Ms. Stoll, who, like Dr. McKeon, was among the coauthors of the alliance’s guidelines on best practices in care transitions. Ms. Stoll also serves on the AAS board as crisis services division chair.* 

The National Action Alliance for Suicide Prevention is a public/private partnership whose goal is to advance the National Strategy for Suicide Prevention, which was developed by the alliance and the U.S. Surgeon General. The alliance includes mental health professionals as well as influential leaders from the military, journalism, entertainment, railroad, health insurance, law enforcement, defense, education, technology, and other industries.

Dr. McKeon and Ms. Stall were joined by Karen Johnson, MSW, another coauthor of the guidelines. They shared highlights of the report.

Inpatient provider strategies

Discharge and crisis safety planning should begin upon admission, according to Ms. Johnson, senior vice president for clinical services and division compliance at Universal Health Services, which owns and operates more than 200 behavioral health facilities across the United States.

Inpatient and outpatient care providers need to sit down and develop collaborative protocols and negotiate a memorandum of understanding regarding expectations, which absolutely must include procedures to ensure timely electronic delivery of medical records and other key documents to the outpatient care providers. The inpatient providers need to work collaboratively with the patient, family, and community support resources to develop a safety plan – including reduced access to lethal mean – as part of predischarge planning.

Among the strategies routinely employed on the inpatient side at Universal Health Services are advance scheduling of an initial outpatient appointment within 24-72 hours post discharge. Also, someone on the inpatient team is tasked with connecting with the outpatient provider prior to discharge to develop rapport.

“If our outpatient providers are located in our facility, as many of them are, we ask them to come in and attend inpatient team meetings to identify and meet with patients who are appropriate for continuing care in outpatient settings,” she explained. “A soft, warm handoff is critical.”

At these team meetings, the appropriateness of step-down care in the form of partial hospitalization or intensive outpatient care is weighed. Someone from the inpatient side is charged with maintaining contact with the patient until after the first outpatient appointment. Ongoing caring contact in the form of brief, encouraging postcards, emails, or texts that do not require a response from the patient should be maintained for several months.
 

Strategies for outpatient providers

Ms. Stoll is a big believer in the guideline-recommended practice of notifying the inpatient provider that the patient kept the outpatient appointment, along with having a system for red-flagging no-shows for prompt follow-up by a crisis management team.

She and her colleagues at Centerstone Health have conducted two studies of an intensive patient outreach program designed for the first 30 days of the care transition. The program included many elements of the alliance’s best practices guidelines. The yearlong first study, funded by Blue Cross/Blue Shield of Tennessee, documented zero suicides and 92% freedom from emergency department visits during the care transition period, along with greater than $400,000 savings in health care costs, compared with usual care. The second study, funded by SAMHSA, showed much the same over a 2-year period.

She emphasized that this was not a high-tech, intensive intervention. She characterized it, instead as “high-touch follow-up.

“It’s some staff and a phone and a laptop, nothing fancy, just a person who’s competent and confident and skilled with a laptop. With that, you can do some pretty amazing stuff: Get people what they need, keep them alive, and oh, guess what? You can also save a lot of health care dollars that can be put back into the system,” Ms. Stoll said.

She recognizes that it’s a lot to ask busy outpatient providers to leave their practice during the workday to participate in inpatient team meetings addressing discharge planning, as recommended in the alliance guidelines. But in this regard, she sees a silver lining to the COVID-19 pandemic, in that it forces health professionals to rely upon newly opened channels of telemedicine.

“COVID-19 is giving us an opportunity to do things in a different way. Things don’t just have to be done in person. Now that we’ve opened up new channels of telehealth, I’m really excited that we’re almost in a beta test that we’ve dreamed about for decades, where we can do things in a more innovative way,” she said.

Dr. McKeon agreed that reimbursement issues have long impeded efforts to improve the inpatient to outpatient care transition. He added that it will be really important that adequate reimbursement of remote forms of care remain in place after COVID-19 fades.

“This is exactly the kind of thing that’s needed to improve care transitions,” according to Dr. McKeon.

*This story was updated 7/9/2020.

bjancin@mdedge.com

The care transition period between inpatient psychiatric hospitalization and initiation of outpatient mental health services is a time of extraordinarily heightened suicide risk that has been woefully neglected, according to speakers from the National Action Alliance for Suicide Prevention at the virtual annual meeting of the American Association of Suicidology.

This transition period traditionally has been a time when nobody really takes responsibility for patient care. In an effort to close this potentially deadly gap in services, the alliance recently has issued a report entitled, “Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care.” The recommendations focus on specific, innovative, evidence-based strategies that health care systems can use to prevent patients from falling through the cracks in care, mainly by implementing protocols aimed at fostering interorganizational teamwork between inpatient and outpatient behavioral health services.

“I believe that improving care transitions in the United States is the area where we can likely save the most lives. It’s within our grasp if we can just do this better,” declared Richard McKeon, PhD, MPH, chief of the Suicide Prevention Branch at the Center for Mental Health Services within SAMHSA, the Substance Abuse and Mental Health Services Administration.

He cited a recent meta-analysis that concluded that the risk of suicide during the first week post discharge after psychiatric hospitalization is a staggering 300 times greater than in the general population, while in the first month, the risk is increased 200-fold. The meta-analysis included 29 studies encompassing 3,551 suicides during the first month and 24 studies reporting 1,928 suicides during the first week post discharge (BMJ Open. 2019 Mar 23;9[3]:e023883. doi: 10.1136/bmjopen-2018-023883).

Everyone in the mental health field as well as patients and their families should know those statistics, but they don’t.

“I think it’s natural for people to think someone who’s been discharged from an inpatient unit or the emergency department is not at risk, when in reality it’s still a high-risk time. Suicide risk is not like a light switch that you can just switch off,” the clinical psychologist observed.

He cited other harrowing statistics that underscore the vast problem of poor care transitions. Nationally, fully one-third of patients don’t complete a single outpatient visit within the first 30 days after discharge from inpatient behavioral health care. And one in seven people who die by suicide have had contact with inpatient mental health services in the year before they died.

“That doesn’t mean that inpatient care did not do everything that they could do. What it does reflect is the need to make sure that there’s follow-up care after inpatient discharge. Too often, people don’t get the follow-up care that they need. And the research literature is clear that intervention can save lives,” Dr. McKeon said.

Panelist Becky Stoll, LCSW, vice president for crisis and disaster management at Centerstone Health in Nashville, Tenn., noted, “We see a lot of no-shows on the outpatient side, because nobody ever asked the patients if they can actually get to the outpatient appointment that’s been made.

“We have got to figure out this care transition and do better. The road to mental health is paved with Swiss cheese. There are so many holes to fall into, even if you know how to navigate the system – and most of the people we’re serving don’t know how,” observed Ms. Stoll, who, like Dr. McKeon, was among the coauthors of the alliance’s guidelines on best practices in care transitions. Ms. Stoll also serves on the AAS board as crisis services division chair.* 

The National Action Alliance for Suicide Prevention is a public/private partnership whose goal is to advance the National Strategy for Suicide Prevention, which was developed by the alliance and the U.S. Surgeon General. The alliance includes mental health professionals as well as influential leaders from the military, journalism, entertainment, railroad, health insurance, law enforcement, defense, education, technology, and other industries.

Dr. McKeon and Ms. Stall were joined by Karen Johnson, MSW, another coauthor of the guidelines. They shared highlights of the report.

Inpatient provider strategies

Discharge and crisis safety planning should begin upon admission, according to Ms. Johnson, senior vice president for clinical services and division compliance at Universal Health Services, which owns and operates more than 200 behavioral health facilities across the United States.

Inpatient and outpatient care providers need to sit down and develop collaborative protocols and negotiate a memorandum of understanding regarding expectations, which absolutely must include procedures to ensure timely electronic delivery of medical records and other key documents to the outpatient care providers. The inpatient providers need to work collaboratively with the patient, family, and community support resources to develop a safety plan – including reduced access to lethal mean – as part of predischarge planning.

Among the strategies routinely employed on the inpatient side at Universal Health Services are advance scheduling of an initial outpatient appointment within 24-72 hours post discharge. Also, someone on the inpatient team is tasked with connecting with the outpatient provider prior to discharge to develop rapport.

“If our outpatient providers are located in our facility, as many of them are, we ask them to come in and attend inpatient team meetings to identify and meet with patients who are appropriate for continuing care in outpatient settings,” she explained. “A soft, warm handoff is critical.”

At these team meetings, the appropriateness of step-down care in the form of partial hospitalization or intensive outpatient care is weighed. Someone from the inpatient side is charged with maintaining contact with the patient until after the first outpatient appointment. Ongoing caring contact in the form of brief, encouraging postcards, emails, or texts that do not require a response from the patient should be maintained for several months.
 

Strategies for outpatient providers

Ms. Stoll is a big believer in the guideline-recommended practice of notifying the inpatient provider that the patient kept the outpatient appointment, along with having a system for red-flagging no-shows for prompt follow-up by a crisis management team.

She and her colleagues at Centerstone Health have conducted two studies of an intensive patient outreach program designed for the first 30 days of the care transition. The program included many elements of the alliance’s best practices guidelines. The yearlong first study, funded by Blue Cross/Blue Shield of Tennessee, documented zero suicides and 92% freedom from emergency department visits during the care transition period, along with greater than $400,000 savings in health care costs, compared with usual care. The second study, funded by SAMHSA, showed much the same over a 2-year period.

She emphasized that this was not a high-tech, intensive intervention. She characterized it, instead as “high-touch follow-up.

“It’s some staff and a phone and a laptop, nothing fancy, just a person who’s competent and confident and skilled with a laptop. With that, you can do some pretty amazing stuff: Get people what they need, keep them alive, and oh, guess what? You can also save a lot of health care dollars that can be put back into the system,” Ms. Stoll said.

She recognizes that it’s a lot to ask busy outpatient providers to leave their practice during the workday to participate in inpatient team meetings addressing discharge planning, as recommended in the alliance guidelines. But in this regard, she sees a silver lining to the COVID-19 pandemic, in that it forces health professionals to rely upon newly opened channels of telemedicine.

“COVID-19 is giving us an opportunity to do things in a different way. Things don’t just have to be done in person. Now that we’ve opened up new channels of telehealth, I’m really excited that we’re almost in a beta test that we’ve dreamed about for decades, where we can do things in a more innovative way,” she said.

Dr. McKeon agreed that reimbursement issues have long impeded efforts to improve the inpatient to outpatient care transition. He added that it will be really important that adequate reimbursement of remote forms of care remain in place after COVID-19 fades.

“This is exactly the kind of thing that’s needed to improve care transitions,” according to Dr. McKeon.

*This story was updated 7/9/2020.

bjancin@mdedge.com

The care transition period between inpatient psychiatric hospitalization and initiation of outpatient mental health services is a time of extraordinarily heightened suicide risk that has been woefully neglected, according to speakers from the National Action Alliance for Suicide Prevention at the virtual annual meeting of the American Association of Suicidology.

This transition period traditionally has been a time when nobody really takes responsibility for patient care. In an effort to close this potentially deadly gap in services, the alliance recently has issued a report entitled, “Best Practices in Care Transitions for Individuals with Suicide Risk: Inpatient Care to Outpatient Care.” The recommendations focus on specific, innovative, evidence-based strategies that health care systems can use to prevent patients from falling through the cracks in care, mainly by implementing protocols aimed at fostering interorganizational teamwork between inpatient and outpatient behavioral health services.

“I believe that improving care transitions in the United States is the area where we can likely save the most lives. It’s within our grasp if we can just do this better,” declared Richard McKeon, PhD, MPH, chief of the Suicide Prevention Branch at the Center for Mental Health Services within SAMHSA, the Substance Abuse and Mental Health Services Administration.

He cited a recent meta-analysis that concluded that the risk of suicide during the first week post discharge after psychiatric hospitalization is a staggering 300 times greater than in the general population, while in the first month, the risk is increased 200-fold. The meta-analysis included 29 studies encompassing 3,551 suicides during the first month and 24 studies reporting 1,928 suicides during the first week post discharge (BMJ Open. 2019 Mar 23;9[3]:e023883. doi: 10.1136/bmjopen-2018-023883).

Everyone in the mental health field as well as patients and their families should know those statistics, but they don’t.

“I think it’s natural for people to think someone who’s been discharged from an inpatient unit or the emergency department is not at risk, when in reality it’s still a high-risk time. Suicide risk is not like a light switch that you can just switch off,” the clinical psychologist observed.

He cited other harrowing statistics that underscore the vast problem of poor care transitions. Nationally, fully one-third of patients don’t complete a single outpatient visit within the first 30 days after discharge from inpatient behavioral health care. And one in seven people who die by suicide have had contact with inpatient mental health services in the year before they died.

“That doesn’t mean that inpatient care did not do everything that they could do. What it does reflect is the need to make sure that there’s follow-up care after inpatient discharge. Too often, people don’t get the follow-up care that they need. And the research literature is clear that intervention can save lives,” Dr. McKeon said.

Panelist Becky Stoll, LCSW, vice president for crisis and disaster management at Centerstone Health in Nashville, Tenn., noted, “We see a lot of no-shows on the outpatient side, because nobody ever asked the patients if they can actually get to the outpatient appointment that’s been made.

“We have got to figure out this care transition and do better. The road to mental health is paved with Swiss cheese. There are so many holes to fall into, even if you know how to navigate the system – and most of the people we’re serving don’t know how,” observed Ms. Stoll, who, like Dr. McKeon, was among the coauthors of the alliance’s guidelines on best practices in care transitions. Ms. Stoll also serves on the AAS board as crisis services division chair.* 

The National Action Alliance for Suicide Prevention is a public/private partnership whose goal is to advance the National Strategy for Suicide Prevention, which was developed by the alliance and the U.S. Surgeon General. The alliance includes mental health professionals as well as influential leaders from the military, journalism, entertainment, railroad, health insurance, law enforcement, defense, education, technology, and other industries.

Dr. McKeon and Ms. Stall were joined by Karen Johnson, MSW, another coauthor of the guidelines. They shared highlights of the report.

Inpatient provider strategies

Discharge and crisis safety planning should begin upon admission, according to Ms. Johnson, senior vice president for clinical services and division compliance at Universal Health Services, which owns and operates more than 200 behavioral health facilities across the United States.

Inpatient and outpatient care providers need to sit down and develop collaborative protocols and negotiate a memorandum of understanding regarding expectations, which absolutely must include procedures to ensure timely electronic delivery of medical records and other key documents to the outpatient care providers. The inpatient providers need to work collaboratively with the patient, family, and community support resources to develop a safety plan – including reduced access to lethal mean – as part of predischarge planning.

Among the strategies routinely employed on the inpatient side at Universal Health Services are advance scheduling of an initial outpatient appointment within 24-72 hours post discharge. Also, someone on the inpatient team is tasked with connecting with the outpatient provider prior to discharge to develop rapport.

“If our outpatient providers are located in our facility, as many of them are, we ask them to come in and attend inpatient team meetings to identify and meet with patients who are appropriate for continuing care in outpatient settings,” she explained. “A soft, warm handoff is critical.”

At these team meetings, the appropriateness of step-down care in the form of partial hospitalization or intensive outpatient care is weighed. Someone from the inpatient side is charged with maintaining contact with the patient until after the first outpatient appointment. Ongoing caring contact in the form of brief, encouraging postcards, emails, or texts that do not require a response from the patient should be maintained for several months.
 

Strategies for outpatient providers

Ms. Stoll is a big believer in the guideline-recommended practice of notifying the inpatient provider that the patient kept the outpatient appointment, along with having a system for red-flagging no-shows for prompt follow-up by a crisis management team.

She and her colleagues at Centerstone Health have conducted two studies of an intensive patient outreach program designed for the first 30 days of the care transition. The program included many elements of the alliance’s best practices guidelines. The yearlong first study, funded by Blue Cross/Blue Shield of Tennessee, documented zero suicides and 92% freedom from emergency department visits during the care transition period, along with greater than $400,000 savings in health care costs, compared with usual care. The second study, funded by SAMHSA, showed much the same over a 2-year period.

She emphasized that this was not a high-tech, intensive intervention. She characterized it, instead as “high-touch follow-up.

“It’s some staff and a phone and a laptop, nothing fancy, just a person who’s competent and confident and skilled with a laptop. With that, you can do some pretty amazing stuff: Get people what they need, keep them alive, and oh, guess what? You can also save a lot of health care dollars that can be put back into the system,” Ms. Stoll said.

She recognizes that it’s a lot to ask busy outpatient providers to leave their practice during the workday to participate in inpatient team meetings addressing discharge planning, as recommended in the alliance guidelines. But in this regard, she sees a silver lining to the COVID-19 pandemic, in that it forces health professionals to rely upon newly opened channels of telemedicine.

“COVID-19 is giving us an opportunity to do things in a different way. Things don’t just have to be done in person. Now that we’ve opened up new channels of telehealth, I’m really excited that we’re almost in a beta test that we’ve dreamed about for decades, where we can do things in a more innovative way,” she said.

Dr. McKeon agreed that reimbursement issues have long impeded efforts to improve the inpatient to outpatient care transition. He added that it will be really important that adequate reimbursement of remote forms of care remain in place after COVID-19 fades.

“This is exactly the kind of thing that’s needed to improve care transitions,” according to Dr. McKeon.

*This story was updated 7/9/2020.

bjancin@mdedge.com

Danicamtiv, a novel oral selective cardiac myosin activator, demonstrated promising beneficial effects on left ventricular systolic function coupled with marked improvements in left atrial volume and function in patients with heart failure with reduced ejection fraction in a phase 2a clinical trial, Adriaan A. Voors, MD, PhD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Importantly, these improvements weren’t accompanied by any unwelcome significant increase in diastolic stiffness, added Dr. Voors, a cardiologist at the University of Groningen (the Netherlands).

This is a drug whose novel mechanism of action could make it a good fit in combination with existing guideline-recommended therapies known to improve morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), none of which do what danicamtiv does: namely, activates cardiac myosin by enhancing myofibrillar adenosine triphosphatase activity, thereby boosting intrinsic myocardial contractility without any impact upon calcium homeostasis, he explained.

Dr. Voors reported on 40 patients with stable HFrEF and a left ventricular ejection fraction of 35% or less, all on background guideline-directed medical therapy. They were randomized double blind to 7 days of danicamtiv at 50, 75, or 100 mg twice daily, or placebo. A total of 489 ECGs were performed in conjunction with blood draws to measure plasma drug concentrations during the study.

Danicamtiv significantly improved left ventricular stroke volume and global longitudinal and circumferential strain in plasma drug concentration–dependent fashion, while simultaneously decreasing left ventricular end-systolic and end-diastolic diameters. Danicamtiv increased systolic ejection time from 286 milliseconds at baseline by an additional placebo-corrected 15, 36, and 48 milliseconds in patients with low, mid-range, and high drug concentrations.

The cardiac myosin activator’s concentration-dependent salutary effects on left atrial (LA) parameters in this brief study were intriguing, since LA function is often compromised in patients with heart failure and has been shown in prior observational studies to independently predict cardiovascular outcomes, the cardiologist noted. The favorable changes in response to danicamtiv included a reduction in LA minimal volume index and an increase in LA emptying fraction. Also, there were marked improvements in LA function index, by 6.1 and 5.8 points, respectively, in patients with mid- and high drug concentrations, from a baseline of 26 points.

Holter monitoring revealed no increased risk of atrial or ventricular arrhythmias in study participants.

Treatment-emergent adverse events were mild and/or unrelated to treatment and showed no particular pattern. The one serious adverse event in the study was a case of hyperkalemia deemed by investigators to be unrelated to treatment.

Seven of 30 danicamtiv-treated patients developed mild, transient, asymptomatic increases in serum cardiac troponin I and/or high-sensitivity troponin T. Dr. Voors said the significance of this must await further examination in larger clinical trials. A phase 2 clinical trial in patients with HFrEF and paroxysmal or persistent atrial fibrillation is planned in order to learn if chronic therapy with danicamtiv results in sustained LA remodeling and clinical benefits. Another planned phase 2 study will be conducted in patients with selected forms of genetic dilated cardiomyopathy.

Because danicamtiv appears to have no effects on blood pressure, renal function, or electrolytes, Dr. Voors speculated that the drug might prove to be an attractive therapeutic option in patients with advanced refractory heart failure, who often have low blood pressure, poor renal function, and a very low left ventricular ejection fraction.

Discussant Thomas Thum, MD, PhD, commented that danicamtiv has definitely earned an opportunity to show what it can do in larger, long-term clinical trials. He was impressed by the significant increase in systolic ejection time, a good marker for cardiac contractility. But he added that the troponin signal warrants careful scrutiny.

“The slight increase over baseline in the phase 2a study was not correlated with any ECG changes or clinical symptoms. However, whether this is a detrimental biomarker sign of a silent harm to the heart remains to be investigated,” said Dr. Thum, a cardiologist at the Institute of Molecular and Translational Therapeutic Strategies at Hannover (Germany) Medical School.

The phase 2a study finding of a plasma drug concentration–dependent prolongation in isovolumetric relaxation time “warrants some caution in future clinical development in patients with impaired diastolic function,” he added.

Simultaneous with Dr. Voors’ presentation, the study results were published online (Eur J Heart Fail. 2020 Jun 19. doi: 10.1002/ejhf.1933).

The danicamtiv study was sponsored by MyoKardia. Dr. Voors reported receiving research funding from and serving as a consultant to MyoKardia and numerous other companies.

bjancin@mdedge.com

Danicamtiv, a novel oral selective cardiac myosin activator, demonstrated promising beneficial effects on left ventricular systolic function coupled with marked improvements in left atrial volume and function in patients with heart failure with reduced ejection fraction in a phase 2a clinical trial, Adriaan A. Voors, MD, PhD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Importantly, these improvements weren’t accompanied by any unwelcome significant increase in diastolic stiffness, added Dr. Voors, a cardiologist at the University of Groningen (the Netherlands).

This is a drug whose novel mechanism of action could make it a good fit in combination with existing guideline-recommended therapies known to improve morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), none of which do what danicamtiv does: namely, activates cardiac myosin by enhancing myofibrillar adenosine triphosphatase activity, thereby boosting intrinsic myocardial contractility without any impact upon calcium homeostasis, he explained.

Dr. Voors reported on 40 patients with stable HFrEF and a left ventricular ejection fraction of 35% or less, all on background guideline-directed medical therapy. They were randomized double blind to 7 days of danicamtiv at 50, 75, or 100 mg twice daily, or placebo. A total of 489 ECGs were performed in conjunction with blood draws to measure plasma drug concentrations during the study.

Danicamtiv significantly improved left ventricular stroke volume and global longitudinal and circumferential strain in plasma drug concentration–dependent fashion, while simultaneously decreasing left ventricular end-systolic and end-diastolic diameters. Danicamtiv increased systolic ejection time from 286 milliseconds at baseline by an additional placebo-corrected 15, 36, and 48 milliseconds in patients with low, mid-range, and high drug concentrations.

The cardiac myosin activator’s concentration-dependent salutary effects on left atrial (LA) parameters in this brief study were intriguing, since LA function is often compromised in patients with heart failure and has been shown in prior observational studies to independently predict cardiovascular outcomes, the cardiologist noted. The favorable changes in response to danicamtiv included a reduction in LA minimal volume index and an increase in LA emptying fraction. Also, there were marked improvements in LA function index, by 6.1 and 5.8 points, respectively, in patients with mid- and high drug concentrations, from a baseline of 26 points.

Holter monitoring revealed no increased risk of atrial or ventricular arrhythmias in study participants.

Treatment-emergent adverse events were mild and/or unrelated to treatment and showed no particular pattern. The one serious adverse event in the study was a case of hyperkalemia deemed by investigators to be unrelated to treatment.

Seven of 30 danicamtiv-treated patients developed mild, transient, asymptomatic increases in serum cardiac troponin I and/or high-sensitivity troponin T. Dr. Voors said the significance of this must await further examination in larger clinical trials. A phase 2 clinical trial in patients with HFrEF and paroxysmal or persistent atrial fibrillation is planned in order to learn if chronic therapy with danicamtiv results in sustained LA remodeling and clinical benefits. Another planned phase 2 study will be conducted in patients with selected forms of genetic dilated cardiomyopathy.

Because danicamtiv appears to have no effects on blood pressure, renal function, or electrolytes, Dr. Voors speculated that the drug might prove to be an attractive therapeutic option in patients with advanced refractory heart failure, who often have low blood pressure, poor renal function, and a very low left ventricular ejection fraction.

Discussant Thomas Thum, MD, PhD, commented that danicamtiv has definitely earned an opportunity to show what it can do in larger, long-term clinical trials. He was impressed by the significant increase in systolic ejection time, a good marker for cardiac contractility. But he added that the troponin signal warrants careful scrutiny.

“The slight increase over baseline in the phase 2a study was not correlated with any ECG changes or clinical symptoms. However, whether this is a detrimental biomarker sign of a silent harm to the heart remains to be investigated,” said Dr. Thum, a cardiologist at the Institute of Molecular and Translational Therapeutic Strategies at Hannover (Germany) Medical School.

The phase 2a study finding of a plasma drug concentration–dependent prolongation in isovolumetric relaxation time “warrants some caution in future clinical development in patients with impaired diastolic function,” he added.

Simultaneous with Dr. Voors’ presentation, the study results were published online (Eur J Heart Fail. 2020 Jun 19. doi: 10.1002/ejhf.1933).

The danicamtiv study was sponsored by MyoKardia. Dr. Voors reported receiving research funding from and serving as a consultant to MyoKardia and numerous other companies.

bjancin@mdedge.com

Danicamtiv, a novel oral selective cardiac myosin activator, demonstrated promising beneficial effects on left ventricular systolic function coupled with marked improvements in left atrial volume and function in patients with heart failure with reduced ejection fraction in a phase 2a clinical trial, Adriaan A. Voors, MD, PhD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Importantly, these improvements weren’t accompanied by any unwelcome significant increase in diastolic stiffness, added Dr. Voors, a cardiologist at the University of Groningen (the Netherlands).

This is a drug whose novel mechanism of action could make it a good fit in combination with existing guideline-recommended therapies known to improve morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), none of which do what danicamtiv does: namely, activates cardiac myosin by enhancing myofibrillar adenosine triphosphatase activity, thereby boosting intrinsic myocardial contractility without any impact upon calcium homeostasis, he explained.

Dr. Voors reported on 40 patients with stable HFrEF and a left ventricular ejection fraction of 35% or less, all on background guideline-directed medical therapy. They were randomized double blind to 7 days of danicamtiv at 50, 75, or 100 mg twice daily, or placebo. A total of 489 ECGs were performed in conjunction with blood draws to measure plasma drug concentrations during the study.

Danicamtiv significantly improved left ventricular stroke volume and global longitudinal and circumferential strain in plasma drug concentration–dependent fashion, while simultaneously decreasing left ventricular end-systolic and end-diastolic diameters. Danicamtiv increased systolic ejection time from 286 milliseconds at baseline by an additional placebo-corrected 15, 36, and 48 milliseconds in patients with low, mid-range, and high drug concentrations.

The cardiac myosin activator’s concentration-dependent salutary effects on left atrial (LA) parameters in this brief study were intriguing, since LA function is often compromised in patients with heart failure and has been shown in prior observational studies to independently predict cardiovascular outcomes, the cardiologist noted. The favorable changes in response to danicamtiv included a reduction in LA minimal volume index and an increase in LA emptying fraction. Also, there were marked improvements in LA function index, by 6.1 and 5.8 points, respectively, in patients with mid- and high drug concentrations, from a baseline of 26 points.

Holter monitoring revealed no increased risk of atrial or ventricular arrhythmias in study participants.

Treatment-emergent adverse events were mild and/or unrelated to treatment and showed no particular pattern. The one serious adverse event in the study was a case of hyperkalemia deemed by investigators to be unrelated to treatment.

Seven of 30 danicamtiv-treated patients developed mild, transient, asymptomatic increases in serum cardiac troponin I and/or high-sensitivity troponin T. Dr. Voors said the significance of this must await further examination in larger clinical trials. A phase 2 clinical trial in patients with HFrEF and paroxysmal or persistent atrial fibrillation is planned in order to learn if chronic therapy with danicamtiv results in sustained LA remodeling and clinical benefits. Another planned phase 2 study will be conducted in patients with selected forms of genetic dilated cardiomyopathy.

Because danicamtiv appears to have no effects on blood pressure, renal function, or electrolytes, Dr. Voors speculated that the drug might prove to be an attractive therapeutic option in patients with advanced refractory heart failure, who often have low blood pressure, poor renal function, and a very low left ventricular ejection fraction.

Discussant Thomas Thum, MD, PhD, commented that danicamtiv has definitely earned an opportunity to show what it can do in larger, long-term clinical trials. He was impressed by the significant increase in systolic ejection time, a good marker for cardiac contractility. But he added that the troponin signal warrants careful scrutiny.

“The slight increase over baseline in the phase 2a study was not correlated with any ECG changes or clinical symptoms. However, whether this is a detrimental biomarker sign of a silent harm to the heart remains to be investigated,” said Dr. Thum, a cardiologist at the Institute of Molecular and Translational Therapeutic Strategies at Hannover (Germany) Medical School.

The phase 2a study finding of a plasma drug concentration–dependent prolongation in isovolumetric relaxation time “warrants some caution in future clinical development in patients with impaired diastolic function,” he added.

Simultaneous with Dr. Voors’ presentation, the study results were published online (Eur J Heart Fail. 2020 Jun 19. doi: 10.1002/ejhf.1933).

The danicamtiv study was sponsored by MyoKardia. Dr. Voors reported receiving research funding from and serving as a consultant to MyoKardia and numerous other companies.

bjancin@mdedge.com

Transcatheter implantation of the Tendyne mitral valve replacement device for treatment of mitral regurgitation in patients at prohibitive surgical risk because of severe mitral annular calcification showed considerable promise in a small feasibility study, Paul Sorajja, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Bruce Jancin/MDedge News

There is a huge unmet need for safe and effective therapies for severe mitral annular calcification (MAC).

“Severe MAC often precludes surgical treatment, and there’s a poor prognosis in patients with MAC and mitral regurgitation when untreated, with 2-year survival of about 60% in some studies,” noted Dr. Sorajja, a cardiologist at the Minneapolis Heart Institute Foundation.

Attempts at repurposing transcatheter aortic valves for use in the mitral location have been largely unsatisfactory, he added.

The 6-month outcomes in the 11 patients who received the Tendyne device in the multicenter U.S. feasibility study featured low rates of mortality and nonfatal adverse events, elimination of mitral regurgitation, marked improvement on quality of life measures, and a mean gradient of 4.1 mm Hg. The acute procedural outcomes were encouraging as well.

“We had technical success in 11 of 11 patients, no procedural mortality or left ventricular outflow tract obstruction, no valve embolization or malposition, and no conversion to open heart surgery,” he said.

There was one death caused by mesenteric ischemia 16 days post Tendyne implantation. One patient experienced a nondisabling stroke at day 4. Two patients developed new-onset atrial fibrillation, one of whom cardioverted to sinus rhythm. And one patient had a moderate paravalvular leak that resolved with placement of a plug at 3 months. There were no MIs.

At baseline, 9 of 11 patients were New York Heart Association functional class III and the others were class II. At 6 months, six patients were class I, four were class II, and one was class III. The average score on the Kansas City Cardiomyopathy Questionnaire improved from 45.9 at baseline to 65.5 at 1 month, 77.4 at 3 months, and 70.3 at 6 months.

This was a highly selected study population with a Society of Thoracic Surgery Predicted Risk of Mortality score of 9.03%. Part of the screening process for study participation involved preprocedural CT imaging with simulated device overlay in order to identify candidates who were likely to have an optimal device fit.

Discussant Francesco Maisano, MD, was impressed by how well this simulation resembled the actual results as depicted in side-by-side pre- and postprocedural CT images presented by Dr. Sorajja.

“What really surprised me was the correlation between preprocedural simulation data and the actual CT scan after the procedure. This trial shows that the simulation works, and also that Tendyne is a great alternative to aortic valve-in-MAC for these very-high-risk patients,” said Dr. Maisano, professor of cardiac surgery at the University of Zürich and a pioneer of catheter-based mitral and tricuspid interventions.

Earlier this year the Tendyne device was approved in Europe for patients with mitral regurgitation who aren’t candidates for surgical valve replacement or transcatheter mitral valve repair. The approval does not, however, extend to MAC. The Abbott device remains investigational in the United States, where the pivotal SUMMIT trial is underway. In one arm of the trial, patients with mitral regurgitation are being randomized to the investigational Tendyne device or to Abbott’s MitraClip, which is approved for that indication. In the other arm, patients with severe MAC at prohibitive surgical risk will get the Tendyne device. Results are expected in 2020.

Dr. Sorajja reported receiving research grants from and serving as a consultant to Abbott, the feasibility study sponsor, as well as to several other medical device companies, as did Dr. Maisano.

bjancin@mdedge.com

Transcatheter implantation of the Tendyne mitral valve replacement device for treatment of mitral regurgitation in patients at prohibitive surgical risk because of severe mitral annular calcification showed considerable promise in a small feasibility study, Paul Sorajja, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Bruce Jancin/MDedge News

There is a huge unmet need for safe and effective therapies for severe mitral annular calcification (MAC).

“Severe MAC often precludes surgical treatment, and there’s a poor prognosis in patients with MAC and mitral regurgitation when untreated, with 2-year survival of about 60% in some studies,” noted Dr. Sorajja, a cardiologist at the Minneapolis Heart Institute Foundation.

Attempts at repurposing transcatheter aortic valves for use in the mitral location have been largely unsatisfactory, he added.

The 6-month outcomes in the 11 patients who received the Tendyne device in the multicenter U.S. feasibility study featured low rates of mortality and nonfatal adverse events, elimination of mitral regurgitation, marked improvement on quality of life measures, and a mean gradient of 4.1 mm Hg. The acute procedural outcomes were encouraging as well.

“We had technical success in 11 of 11 patients, no procedural mortality or left ventricular outflow tract obstruction, no valve embolization or malposition, and no conversion to open heart surgery,” he said.

There was one death caused by mesenteric ischemia 16 days post Tendyne implantation. One patient experienced a nondisabling stroke at day 4. Two patients developed new-onset atrial fibrillation, one of whom cardioverted to sinus rhythm. And one patient had a moderate paravalvular leak that resolved with placement of a plug at 3 months. There were no MIs.

At baseline, 9 of 11 patients were New York Heart Association functional class III and the others were class II. At 6 months, six patients were class I, four were class II, and one was class III. The average score on the Kansas City Cardiomyopathy Questionnaire improved from 45.9 at baseline to 65.5 at 1 month, 77.4 at 3 months, and 70.3 at 6 months.

This was a highly selected study population with a Society of Thoracic Surgery Predicted Risk of Mortality score of 9.03%. Part of the screening process for study participation involved preprocedural CT imaging with simulated device overlay in order to identify candidates who were likely to have an optimal device fit.

Discussant Francesco Maisano, MD, was impressed by how well this simulation resembled the actual results as depicted in side-by-side pre- and postprocedural CT images presented by Dr. Sorajja.

“What really surprised me was the correlation between preprocedural simulation data and the actual CT scan after the procedure. This trial shows that the simulation works, and also that Tendyne is a great alternative to aortic valve-in-MAC for these very-high-risk patients,” said Dr. Maisano, professor of cardiac surgery at the University of Zürich and a pioneer of catheter-based mitral and tricuspid interventions.

Earlier this year the Tendyne device was approved in Europe for patients with mitral regurgitation who aren’t candidates for surgical valve replacement or transcatheter mitral valve repair. The approval does not, however, extend to MAC. The Abbott device remains investigational in the United States, where the pivotal SUMMIT trial is underway. In one arm of the trial, patients with mitral regurgitation are being randomized to the investigational Tendyne device or to Abbott’s MitraClip, which is approved for that indication. In the other arm, patients with severe MAC at prohibitive surgical risk will get the Tendyne device. Results are expected in 2020.

Dr. Sorajja reported receiving research grants from and serving as a consultant to Abbott, the feasibility study sponsor, as well as to several other medical device companies, as did Dr. Maisano.

bjancin@mdedge.com

Transcatheter implantation of the Tendyne mitral valve replacement device for treatment of mitral regurgitation in patients at prohibitive surgical risk because of severe mitral annular calcification showed considerable promise in a small feasibility study, Paul Sorajja, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Bruce Jancin/MDedge News

There is a huge unmet need for safe and effective therapies for severe mitral annular calcification (MAC).

“Severe MAC often precludes surgical treatment, and there’s a poor prognosis in patients with MAC and mitral regurgitation when untreated, with 2-year survival of about 60% in some studies,” noted Dr. Sorajja, a cardiologist at the Minneapolis Heart Institute Foundation.

Attempts at repurposing transcatheter aortic valves for use in the mitral location have been largely unsatisfactory, he added.

The 6-month outcomes in the 11 patients who received the Tendyne device in the multicenter U.S. feasibility study featured low rates of mortality and nonfatal adverse events, elimination of mitral regurgitation, marked improvement on quality of life measures, and a mean gradient of 4.1 mm Hg. The acute procedural outcomes were encouraging as well.

“We had technical success in 11 of 11 patients, no procedural mortality or left ventricular outflow tract obstruction, no valve embolization or malposition, and no conversion to open heart surgery,” he said.

There was one death caused by mesenteric ischemia 16 days post Tendyne implantation. One patient experienced a nondisabling stroke at day 4. Two patients developed new-onset atrial fibrillation, one of whom cardioverted to sinus rhythm. And one patient had a moderate paravalvular leak that resolved with placement of a plug at 3 months. There were no MIs.

At baseline, 9 of 11 patients were New York Heart Association functional class III and the others were class II. At 6 months, six patients were class I, four were class II, and one was class III. The average score on the Kansas City Cardiomyopathy Questionnaire improved from 45.9 at baseline to 65.5 at 1 month, 77.4 at 3 months, and 70.3 at 6 months.

This was a highly selected study population with a Society of Thoracic Surgery Predicted Risk of Mortality score of 9.03%. Part of the screening process for study participation involved preprocedural CT imaging with simulated device overlay in order to identify candidates who were likely to have an optimal device fit.

Discussant Francesco Maisano, MD, was impressed by how well this simulation resembled the actual results as depicted in side-by-side pre- and postprocedural CT images presented by Dr. Sorajja.

“What really surprised me was the correlation between preprocedural simulation data and the actual CT scan after the procedure. This trial shows that the simulation works, and also that Tendyne is a great alternative to aortic valve-in-MAC for these very-high-risk patients,” said Dr. Maisano, professor of cardiac surgery at the University of Zürich and a pioneer of catheter-based mitral and tricuspid interventions.

Earlier this year the Tendyne device was approved in Europe for patients with mitral regurgitation who aren’t candidates for surgical valve replacement or transcatheter mitral valve repair. The approval does not, however, extend to MAC. The Abbott device remains investigational in the United States, where the pivotal SUMMIT trial is underway. In one arm of the trial, patients with mitral regurgitation are being randomized to the investigational Tendyne device or to Abbott’s MitraClip, which is approved for that indication. In the other arm, patients with severe MAC at prohibitive surgical risk will get the Tendyne device. Results are expected in 2020.

Dr. Sorajja reported receiving research grants from and serving as a consultant to Abbott, the feasibility study sponsor, as well as to several other medical device companies, as did Dr. Maisano.

bjancin@mdedge.com

Tirofiban is far superior to cangrelor at achieving rapid and potent inhibition of platelet aggregation in patients undergoing primary percutaneous coronary intervention for ST-elevation MI.

Frontline Medical News

And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).

He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.

But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.

The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.

The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).

Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.

The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.

FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.

Bruce Jancin/Frontline Medical News

Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.

“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.

Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.

However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.

Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).

Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.

bjancin@mdedge.com

Tirofiban is far superior to cangrelor at achieving rapid and potent inhibition of platelet aggregation in patients undergoing primary percutaneous coronary intervention for ST-elevation MI.

Frontline Medical News

And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).

He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.

But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.

The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.

The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).

Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.

The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.

FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.

Bruce Jancin/Frontline Medical News

Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.

“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.

Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.

However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.

Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).

Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.

bjancin@mdedge.com

Tirofiban is far superior to cangrelor at achieving rapid and potent inhibition of platelet aggregation in patients undergoing primary percutaneous coronary intervention for ST-elevation MI.

Frontline Medical News

And cangrelor, in turn, is superior to oral prasugrel, according to the randomized FABOLUS FASTER trial, Marco Valgimigli, MD, PhD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

Moreover, contrary to conventional wisdom, chewed prasugrel (Effient) proved no better than swallowing the tablets whole for platelet inhibition, said Dr. Valgimigli, an interventional cardiologist at the University of Bern (Switzerland).

He explained that standard administration of the newer oral P2Y12 inhibitors prasugrel and ticagrelor (Brilinta) in patients undergoing percutaneous coronary intervention (PCI) for ST-elevation MI (STEMI) does not provide optimal early inhibition of platelet aggregation. The parenteral antiplatelet drugs tirofiban and cangrelor have been shown to provide faster and more prolonged inhibition of platelet aggregation than the oral P2Y12 inhibitors.

But there has been no head-to-head comparative data for the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat) and the P2Y12 inhibitor cangrelor (Kengreal) in the setting of primary PCI for STEMI. This was the impetus for FABOLUS FASTER, the first study to compare the pharmacodynamic effects of the two parenteral antiplatelet agents. The trial also looked at how these potent parenteral drugs, compared with chewed prasugrel, another previously unexamined yet highly practical issue.

The three-center, multinational, open-label FABOLUS FASTER trial randomized 122 patients undergoing primary PCI for STEMI to one of three arms: a standard intravenous bolus and 2-hour infusion of either the P2Y12 inhibitor cangrelor (Kengreal) or the glycoprotein IIb/IIIA inhibitor tirofiban (Aggrastat), followed in either case by 60 mg of oral prasugrel, or a third arm in which patients didn’t receive either drug but were instead randomized to a 60-mg loading dose of chewed or whole prasugrel tablets.

The primary study endpoint was inhibition of platelet aggregation at 30 minutes as measured by light transmittance aggregometry in response to 20 mcmol/L of adenosine diphosphate (ADP).

Tirofiban was the unequivocal winner with 95% inhibition, as compared with 34.1% with cangrelor, 10.5% with chewed prasugrel, and 6.3% with prasugrel swallowed whole, even though the concentration of prasugrel’s active metabolite was far greater at 62.3 ng/mL after prasugrel was chewed, compared with 17.1 ng/mL when swallowed in integral tablet form.

The rate of nonresponsiveness to tirofiban as defined by greater than 59% platelet aggregation was zero for tirofiban during its 2-hour infusion, then a scant 8% thereafter during repeated testing at 3 and 4-6 hours. In contrast, the cangrelor nonresponsiveness rate was 50%-58% during the 2-hour infusion, rising to 82% at 3 hours.

FABOLUS FASTER, while not powered for clinical endpoints, might nevertheless have important clinical implications, according to Dr. Valgimigli. First, the superiority of the intravenous drugs tirofiban and cangrelor over prasugrel for early, strong platelet inhibition underscores the importance of giving parenteral antiplatelet drugs over oral therapy during the acute phase of STEMI therapy. Moreover, tirofiban’s outstanding performance – and the high residual platelet reactivity associated with cangrelor – makes a strong case for large comparative, randomized trials of the two drugs, with hard clinical endpoints.

Bruce Jancin/Frontline Medical News

Discussant Christoph K. Naber, MD, PhD, opined that he personally doesn’t consider the FABOLUS FASTER results practice changing, for a couple of reasons.

“Platelet inhibition measured by ADP in vitro is not necessarily related to true effects in vivo. We know that platelets are activated by multiple mechanisms, and the ADP pathway is just one of them,” said Dr. Naber, an interventional cardiologist at the Wilhemshaven (Germany) Clinic.

Also, there’s a good reason why no glycoprotein IIb/IIIA inhibitors are approved for treatment of STEMI, and why tirofiban, despite its impressive antiplatelet effects, is currently largely reserved for bailout situations, such as complex lesions with large thrombus burden. It’s because tirofiban’s potent antiplatelet activity is accompanied by a high risk of bleeding, he added.

However, Dr. Valgimigli noted that this conviction about excessive bleeding risk is mainly based on older studies in which glycoprotein IIb/IIIA inhibitors were administered for prolonged duration through femoral access sites. He argued that it’s time for large clinical trials examining the risk/benefit ratio of short infusion of these agents in the contemporary practice of primary PCI for STEMI.

Simultaneously with Dr. Valgimigli’s presentation, the FABOLUS FASTER results were published online (Circulation. 2020 Jun 27; doi: 10.1161/CIRCULATIONAHA.120.046928).

Dr. Valgimigli reported that Medicure, the sponsor of the FABOLUS FASTER trial, provided an institutional research grant to conduct the study. He also disclosed receiving research grants and personal fees outside the scope of this study from a dozen pharmaceutical and medical device companies. Dr. Naber reported having no financial conflicts.

bjancin@mdedge.com

A systematic two-stent approach to complex coronary bifurcation lesions led to significantly improved clinical outcomes at 1 year, compared with the long-popular provisional stenting technique, in the first randomized trial to prospectively validate a standardized definition of what constitutes a complex bifurcation.

Since the double-kissing (DK) crush technique was employed in 78% of the systematic two-stent procedures, and the two-stent approach provided superior outcomes, it’s reasonable to infer that the DK crush is the preferred technique in patients with truly complex coronary bifurcation lesions (CBLs), Shao-Liang Chen, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

He presented the results of the DEFINITION II trial, a multinational trial in which 653 patients at 49 medical centers who fulfilled the criteria for complex CBLs were randomized to a systematic two-stent approach or provisional stenting, with a second stent deployed by interventionalists as needed. Dr. Chen, director of the cardiology department and deputy president of Nanjing (China) Medical University, and coworkers had previously published their standardized criteria for CBLs (JACC Cardiovasc Interv. 2014 Nov;7[11]:1266-76), which they developed by analysis of a large bifurcation cohort; however, until the DEFINITION II trial, the criteria had never been used in a prospective randomized trial.

According to the standardized definition developed by Dr. Chen and associates, complex coronary bifurcation lesions must meet one major and two minor criteria.

Major criteria:

• A side branch lesion length of at least 10 mm with a diameter stenosis of 70% or more for distal left main bifurcation lesions.
• For non–left main bifurcation lesions, a side branch diameter stenosis of at least 90% along with a side branch lesion length of at least 10 mm.

Minor criteria:

• Moderate to severe calcification multiple lesions
• Bifurcation angle of <45 degrees or >70 degrees
• Thrombus-containing lesions
• Main vessel residual diameter <2.5 mm
• Main vessel lesion length of at least 25 mm

Interventionalists were strongly encouraged to utilize the DK crush or culotte stenting techniques in patients randomized to the systematic two-stent approach. In contrast, in the provisional stenting group, where 23% of patients received a second stent, that stent was placed using the T and small protrusion technique 64% of the time.

The primary endpoint was the target lesion failure rate at 1-year of follow-up. Target lesion failure was a composite comprising cardiac death, target vessel MI, and clinically driven target vessel revascularization. The rate was 6.1% in the systematic two-stent group and 11.4% with provisional stenting, for a highly significant 48% relative risk reduction. The difference was driven largely by the systematic two-stent group’s lower rates of target vessel MI – 3.0% versus 7.1% with provisional stenting – and target lesion revascularization, with rates of 2.4% and 5.5%, respectively.

“The underlying mechanisms for the increased target vessel MI rate after the provisional stenting technique are unclear, and further study is urgently warranted,” Dr. Chen said.

There were no significant between-group differences in all-cause mortality or cardiac death, although both endpoints were numerically less frequent in the two-stent group.

The primary safety outcome was the 12-month rate of definite or probable stent thrombosis. This occurred in 1.2% of the systematic two-stent group and 2.5% of the provisional stent patients, a nonsignificant difference.

Bruce Jancin/MDedge News

Discussant Davide Capodanno, MD, PhD, declared the DEFINITE II trial to be “another success for this DK crush technique everyone is talking about recently.”

He noted that, in a recent meta-analysis of 21 randomized, controlled trials including 5,711 patients with bifurcation lesions treated using five different percutaneous coronary intervention techniques, DK crush stood out from the pack. Particularly impressive was the finding that the target lesion revascularization rate in patients treated using the DK crush technique was 64% lower than with provisional stenting (JACC Cardiovasc Interv. 2020 Jun 22;13[12]:1432-44).

Dr. Capodanno said that, although the DEFINITE II results were strongly positive in favor of the systematic two-stent approach and DK crush technique, he’s not convinced of the generalizability of the study results.

“These investigators are very expert in this technique. They invented it. They’ve been using it for 10 years. So of course you may expect excellent results when you have masters of this technique,” observed Dr. Capodanno, a cardiologist at the University of Catania (Italy).

Independent replication of the DEFINITE II findings is needed. Fortunately, two ongoing randomized trials are addressing the issue of how to best treat bifurcation lesions. The EBC-MAIN trial is comparing the provisional approach with the systematic two-stent strategy in patients with left main bifurcation lesions; the study will include the DK crush as well as culotte and TAP PCI techniques, with a primary endpoint consisting of the 12-month rate of death, MI, and target lesion revascularization. And the BBK-3 trial will compare systematic two-stent strategies pitting the culotte against the DK crush, with the primary endpoint being the 9-month rate of angiographic restenosis by quantitative coronary angiography.

“After these trials are complete, we’ll probably know much more about the tailoring of bifurcation techniques for particular patients,” according to Dr. Capodanno.

Simultaneous with Dr. Chen’s presentation, the results of the DEFINITION II trial were published online (Eur Heart J. 2020 Jun 26.doi: 10.1093/eurheartj/ehaa543).

Dr. Chen and Dr. Capodanno reported having no financial conflicts of interest regarding the study, which was funded mainly by the National Science Foundation of China.

bjancin@mdedge.com

A systematic two-stent approach to complex coronary bifurcation lesions led to significantly improved clinical outcomes at 1 year, compared with the long-popular provisional stenting technique, in the first randomized trial to prospectively validate a standardized definition of what constitutes a complex bifurcation.

Since the double-kissing (DK) crush technique was employed in 78% of the systematic two-stent procedures, and the two-stent approach provided superior outcomes, it’s reasonable to infer that the DK crush is the preferred technique in patients with truly complex coronary bifurcation lesions (CBLs), Shao-Liang Chen, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

He presented the results of the DEFINITION II trial, a multinational trial in which 653 patients at 49 medical centers who fulfilled the criteria for complex CBLs were randomized to a systematic two-stent approach or provisional stenting, with a second stent deployed by interventionalists as needed. Dr. Chen, director of the cardiology department and deputy president of Nanjing (China) Medical University, and coworkers had previously published their standardized criteria for CBLs (JACC Cardiovasc Interv. 2014 Nov;7[11]:1266-76), which they developed by analysis of a large bifurcation cohort; however, until the DEFINITION II trial, the criteria had never been used in a prospective randomized trial.

According to the standardized definition developed by Dr. Chen and associates, complex coronary bifurcation lesions must meet one major and two minor criteria.

Major criteria:

• A side branch lesion length of at least 10 mm with a diameter stenosis of 70% or more for distal left main bifurcation lesions.
• For non–left main bifurcation lesions, a side branch diameter stenosis of at least 90% along with a side branch lesion length of at least 10 mm.

Minor criteria:

• Moderate to severe calcification multiple lesions
• Bifurcation angle of <45 degrees or >70 degrees
• Thrombus-containing lesions
• Main vessel residual diameter <2.5 mm
• Main vessel lesion length of at least 25 mm

Interventionalists were strongly encouraged to utilize the DK crush or culotte stenting techniques in patients randomized to the systematic two-stent approach. In contrast, in the provisional stenting group, where 23% of patients received a second stent, that stent was placed using the T and small protrusion technique 64% of the time.

The primary endpoint was the target lesion failure rate at 1-year of follow-up. Target lesion failure was a composite comprising cardiac death, target vessel MI, and clinically driven target vessel revascularization. The rate was 6.1% in the systematic two-stent group and 11.4% with provisional stenting, for a highly significant 48% relative risk reduction. The difference was driven largely by the systematic two-stent group’s lower rates of target vessel MI – 3.0% versus 7.1% with provisional stenting – and target lesion revascularization, with rates of 2.4% and 5.5%, respectively.

“The underlying mechanisms for the increased target vessel MI rate after the provisional stenting technique are unclear, and further study is urgently warranted,” Dr. Chen said.

There were no significant between-group differences in all-cause mortality or cardiac death, although both endpoints were numerically less frequent in the two-stent group.

The primary safety outcome was the 12-month rate of definite or probable stent thrombosis. This occurred in 1.2% of the systematic two-stent group and 2.5% of the provisional stent patients, a nonsignificant difference.

Bruce Jancin/MDedge News

Discussant Davide Capodanno, MD, PhD, declared the DEFINITE II trial to be “another success for this DK crush technique everyone is talking about recently.”

He noted that, in a recent meta-analysis of 21 randomized, controlled trials including 5,711 patients with bifurcation lesions treated using five different percutaneous coronary intervention techniques, DK crush stood out from the pack. Particularly impressive was the finding that the target lesion revascularization rate in patients treated using the DK crush technique was 64% lower than with provisional stenting (JACC Cardiovasc Interv. 2020 Jun 22;13[12]:1432-44).

Dr. Capodanno said that, although the DEFINITE II results were strongly positive in favor of the systematic two-stent approach and DK crush technique, he’s not convinced of the generalizability of the study results.

“These investigators are very expert in this technique. They invented it. They’ve been using it for 10 years. So of course you may expect excellent results when you have masters of this technique,” observed Dr. Capodanno, a cardiologist at the University of Catania (Italy).

Independent replication of the DEFINITE II findings is needed. Fortunately, two ongoing randomized trials are addressing the issue of how to best treat bifurcation lesions. The EBC-MAIN trial is comparing the provisional approach with the systematic two-stent strategy in patients with left main bifurcation lesions; the study will include the DK crush as well as culotte and TAP PCI techniques, with a primary endpoint consisting of the 12-month rate of death, MI, and target lesion revascularization. And the BBK-3 trial will compare systematic two-stent strategies pitting the culotte against the DK crush, with the primary endpoint being the 9-month rate of angiographic restenosis by quantitative coronary angiography.

“After these trials are complete, we’ll probably know much more about the tailoring of bifurcation techniques for particular patients,” according to Dr. Capodanno.

Simultaneous with Dr. Chen’s presentation, the results of the DEFINITION II trial were published online (Eur Heart J. 2020 Jun 26.doi: 10.1093/eurheartj/ehaa543).

Dr. Chen and Dr. Capodanno reported having no financial conflicts of interest regarding the study, which was funded mainly by the National Science Foundation of China.

bjancin@mdedge.com

A systematic two-stent approach to complex coronary bifurcation lesions led to significantly improved clinical outcomes at 1 year, compared with the long-popular provisional stenting technique, in the first randomized trial to prospectively validate a standardized definition of what constitutes a complex bifurcation.

Since the double-kissing (DK) crush technique was employed in 78% of the systematic two-stent procedures, and the two-stent approach provided superior outcomes, it’s reasonable to infer that the DK crush is the preferred technique in patients with truly complex coronary bifurcation lesions (CBLs), Shao-Liang Chen, MD, reported at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

He presented the results of the DEFINITION II trial, a multinational trial in which 653 patients at 49 medical centers who fulfilled the criteria for complex CBLs were randomized to a systematic two-stent approach or provisional stenting, with a second stent deployed by interventionalists as needed. Dr. Chen, director of the cardiology department and deputy president of Nanjing (China) Medical University, and coworkers had previously published their standardized criteria for CBLs (JACC Cardiovasc Interv. 2014 Nov;7[11]:1266-76), which they developed by analysis of a large bifurcation cohort; however, until the DEFINITION II trial, the criteria had never been used in a prospective randomized trial.

According to the standardized definition developed by Dr. Chen and associates, complex coronary bifurcation lesions must meet one major and two minor criteria.

Major criteria:

• A side branch lesion length of at least 10 mm with a diameter stenosis of 70% or more for distal left main bifurcation lesions.
• For non–left main bifurcation lesions, a side branch diameter stenosis of at least 90% along with a side branch lesion length of at least 10 mm.

Minor criteria:

• Moderate to severe calcification multiple lesions
• Bifurcation angle of <45 degrees or >70 degrees
• Thrombus-containing lesions
• Main vessel residual diameter <2.5 mm
• Main vessel lesion length of at least 25 mm

Interventionalists were strongly encouraged to utilize the DK crush or culotte stenting techniques in patients randomized to the systematic two-stent approach. In contrast, in the provisional stenting group, where 23% of patients received a second stent, that stent was placed using the T and small protrusion technique 64% of the time.

The primary endpoint was the target lesion failure rate at 1-year of follow-up. Target lesion failure was a composite comprising cardiac death, target vessel MI, and clinically driven target vessel revascularization. The rate was 6.1% in the systematic two-stent group and 11.4% with provisional stenting, for a highly significant 48% relative risk reduction. The difference was driven largely by the systematic two-stent group’s lower rates of target vessel MI – 3.0% versus 7.1% with provisional stenting – and target lesion revascularization, with rates of 2.4% and 5.5%, respectively.

“The underlying mechanisms for the increased target vessel MI rate after the provisional stenting technique are unclear, and further study is urgently warranted,” Dr. Chen said.

There were no significant between-group differences in all-cause mortality or cardiac death, although both endpoints were numerically less frequent in the two-stent group.

The primary safety outcome was the 12-month rate of definite or probable stent thrombosis. This occurred in 1.2% of the systematic two-stent group and 2.5% of the provisional stent patients, a nonsignificant difference.

Bruce Jancin/MDedge News

Discussant Davide Capodanno, MD, PhD, declared the DEFINITE II trial to be “another success for this DK crush technique everyone is talking about recently.”

He noted that, in a recent meta-analysis of 21 randomized, controlled trials including 5,711 patients with bifurcation lesions treated using five different percutaneous coronary intervention techniques, DK crush stood out from the pack. Particularly impressive was the finding that the target lesion revascularization rate in patients treated using the DK crush technique was 64% lower than with provisional stenting (JACC Cardiovasc Interv. 2020 Jun 22;13[12]:1432-44).

Dr. Capodanno said that, although the DEFINITE II results were strongly positive in favor of the systematic two-stent approach and DK crush technique, he’s not convinced of the generalizability of the study results.

“These investigators are very expert in this technique. They invented it. They’ve been using it for 10 years. So of course you may expect excellent results when you have masters of this technique,” observed Dr. Capodanno, a cardiologist at the University of Catania (Italy).

Independent replication of the DEFINITE II findings is needed. Fortunately, two ongoing randomized trials are addressing the issue of how to best treat bifurcation lesions. The EBC-MAIN trial is comparing the provisional approach with the systematic two-stent strategy in patients with left main bifurcation lesions; the study will include the DK crush as well as culotte and TAP PCI techniques, with a primary endpoint consisting of the 12-month rate of death, MI, and target lesion revascularization. And the BBK-3 trial will compare systematic two-stent strategies pitting the culotte against the DK crush, with the primary endpoint being the 9-month rate of angiographic restenosis by quantitative coronary angiography.

“After these trials are complete, we’ll probably know much more about the tailoring of bifurcation techniques for particular patients,” according to Dr. Capodanno.

Simultaneous with Dr. Chen’s presentation, the results of the DEFINITION II trial were published online (Eur Heart J. 2020 Jun 26.doi: 10.1093/eurheartj/ehaa543).

Dr. Chen and Dr. Capodanno reported having no financial conflicts of interest regarding the study, which was funded mainly by the National Science Foundation of China.

bjancin@mdedge.com

Every rheumatologist ought to be comfortable in using a validated gastrointestinal symptom scale for evaluation of gastroesophageal reflux disease in patients with scleroderma, Tracy M. Frech, MD, declared at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

copyright nebari/Thinkstock

About 90% of scleroderma patients will develop GI tract involvement during the course of their connective tissue disease. And while any portion of the GI tract from esophagus to anus can be involved, the most common GI manifestation is gastroesophageal reflux disease (GERD), affecting up to 90% of scleroderma patients, observed Dr. Frech, a rheumatologist and director of the systemic sclerosis clinic at the University of Utah and the George E. Wahlen Department of Veterans Affairs Medical Center, both in Salt Lake City.

“It is essential to ask scleroderma patients questions in order to understand their gastrointestinal tract symptoms. The questionnaires are really critical for us to grade the severity and then properly order tests,” she explained. “The goal is symptom identification, ideally with minimal time burden and at no cost, to guide decisions that move our patients’ care forward.”

Three of the most useful validated instruments for assessment of GERD symptoms in scleroderma patients in routine clinical practice are the GerdQ, the University of California, Los Angeles, Scleroderma Clinical Trial Consortium GI Tract Questionnaire (UCLA GIT) 2.0 reflux scale, and the Patient-Reported Outcomes Measurement Information System (PROMIS) reflux scale.

The GerdQ is a six-item, self-administered questionnaire in which patients specify how many days in the past week they have experienced heartburn, regurgitation, nausea, sleep interference, upper abdominal pain, and need for medication. A free online tool is available for calculating the likelihood of having GERD based upon GerdQ score. A score of 8 or more points out of a possible 18 has the highest sensitivity and specificity for diagnosis of GERD.

The UCLA GIT 2.0 – the most commonly used instrument for GI symptom assessment in scleroderma patients – includes 34 items. It takes 6-8 minutes to complete the whole thing, but patients being assessed for GERD only need answer the eight GERD-specific questions. Six of these eight questions are the same as in the GerdQ. One of the two extra questions asks about difficulty in swallowing solid food, which if answered affirmatively warrants early referral to a gastroenterologist. The other question inquires about any food triggers for the reflux, providing an opportunity for a rheumatologist to educate the patient about the importance of avoiding acidic foods, such as tomatoes, and other food and drink generally considered healthy but which actually exacerbate GERD.

The National Institutes of Health PROMIS scale, the newest of the three instruments, is a 60-item questionnaire; however, only 20 questions relate to reflux and dysphagia and are thus germane to a focused GERD assessment in scleroderma.

When a clinical diagnosis of GERD is made in a scleroderma patient based upon symptoms elicited by questionnaire, guidelines recommend a trial of empiric proton pump inhibitor therapy and behavioral interventions, such as raising the head of the bed, in order to confirm the diagnosis. If the patient reports feeling better after these basic interventions, the diagnosis is confirmed. If not, it’s time to make a referral to a gastroenterologist for specialized care, Dr. Frech said.

Dr. Frech was a coinvestigator in an international, prospective, longitudinal study of patient-reported outcomes measures in 116 patients with scleroderma and GERD. All study participants had to complete the UCLA GIT 2.0, the PROMIS reflux scale, and a third patient-reported GERD measure both before and after the therapeutic intervention. The UCLA GIT 2.0 and PROMIS instruments demonstrated similarly robust sensitivity for identifying changes in GERD symptoms after therapeutic intervention.

“It doesn’t really matter what questionnaire we’re using,” according to the rheumatologist. “But I will point out that there is significant overlap in symptoms among GERD, gastroparesis, functional dyspepsia, and eosinophilic esophagitis, all of which cause symptoms of heartburn and regurgitation. So we don’t want to ask these questions just once, we want to make an intervention and then reask the questions to ensure that we’re continuously moving forward with the gastrointestinal tract management plan.”

Dr. Frech reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

Every rheumatologist ought to be comfortable in using a validated gastrointestinal symptom scale for evaluation of gastroesophageal reflux disease in patients with scleroderma, Tracy M. Frech, MD, declared at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

copyright nebari/Thinkstock

About 90% of scleroderma patients will develop GI tract involvement during the course of their connective tissue disease. And while any portion of the GI tract from esophagus to anus can be involved, the most common GI manifestation is gastroesophageal reflux disease (GERD), affecting up to 90% of scleroderma patients, observed Dr. Frech, a rheumatologist and director of the systemic sclerosis clinic at the University of Utah and the George E. Wahlen Department of Veterans Affairs Medical Center, both in Salt Lake City.

“It is essential to ask scleroderma patients questions in order to understand their gastrointestinal tract symptoms. The questionnaires are really critical for us to grade the severity and then properly order tests,” she explained. “The goal is symptom identification, ideally with minimal time burden and at no cost, to guide decisions that move our patients’ care forward.”

Three of the most useful validated instruments for assessment of GERD symptoms in scleroderma patients in routine clinical practice are the GerdQ, the University of California, Los Angeles, Scleroderma Clinical Trial Consortium GI Tract Questionnaire (UCLA GIT) 2.0 reflux scale, and the Patient-Reported Outcomes Measurement Information System (PROMIS) reflux scale.

The GerdQ is a six-item, self-administered questionnaire in which patients specify how many days in the past week they have experienced heartburn, regurgitation, nausea, sleep interference, upper abdominal pain, and need for medication. A free online tool is available for calculating the likelihood of having GERD based upon GerdQ score. A score of 8 or more points out of a possible 18 has the highest sensitivity and specificity for diagnosis of GERD.

The UCLA GIT 2.0 – the most commonly used instrument for GI symptom assessment in scleroderma patients – includes 34 items. It takes 6-8 minutes to complete the whole thing, but patients being assessed for GERD only need answer the eight GERD-specific questions. Six of these eight questions are the same as in the GerdQ. One of the two extra questions asks about difficulty in swallowing solid food, which if answered affirmatively warrants early referral to a gastroenterologist. The other question inquires about any food triggers for the reflux, providing an opportunity for a rheumatologist to educate the patient about the importance of avoiding acidic foods, such as tomatoes, and other food and drink generally considered healthy but which actually exacerbate GERD.

The National Institutes of Health PROMIS scale, the newest of the three instruments, is a 60-item questionnaire; however, only 20 questions relate to reflux and dysphagia and are thus germane to a focused GERD assessment in scleroderma.

When a clinical diagnosis of GERD is made in a scleroderma patient based upon symptoms elicited by questionnaire, guidelines recommend a trial of empiric proton pump inhibitor therapy and behavioral interventions, such as raising the head of the bed, in order to confirm the diagnosis. If the patient reports feeling better after these basic interventions, the diagnosis is confirmed. If not, it’s time to make a referral to a gastroenterologist for specialized care, Dr. Frech said.

Dr. Frech was a coinvestigator in an international, prospective, longitudinal study of patient-reported outcomes measures in 116 patients with scleroderma and GERD. All study participants had to complete the UCLA GIT 2.0, the PROMIS reflux scale, and a third patient-reported GERD measure both before and after the therapeutic intervention. The UCLA GIT 2.0 and PROMIS instruments demonstrated similarly robust sensitivity for identifying changes in GERD symptoms after therapeutic intervention.

“It doesn’t really matter what questionnaire we’re using,” according to the rheumatologist. “But I will point out that there is significant overlap in symptoms among GERD, gastroparesis, functional dyspepsia, and eosinophilic esophagitis, all of which cause symptoms of heartburn and regurgitation. So we don’t want to ask these questions just once, we want to make an intervention and then reask the questions to ensure that we’re continuously moving forward with the gastrointestinal tract management plan.”

Dr. Frech reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

Every rheumatologist ought to be comfortable in using a validated gastrointestinal symptom scale for evaluation of gastroesophageal reflux disease in patients with scleroderma, Tracy M. Frech, MD, declared at the virtual edition of the American College of Rheumatology’s 2020 State-of-the-Art Clinical Symposium.

copyright nebari/Thinkstock

About 90% of scleroderma patients will develop GI tract involvement during the course of their connective tissue disease. And while any portion of the GI tract from esophagus to anus can be involved, the most common GI manifestation is gastroesophageal reflux disease (GERD), affecting up to 90% of scleroderma patients, observed Dr. Frech, a rheumatologist and director of the systemic sclerosis clinic at the University of Utah and the George E. Wahlen Department of Veterans Affairs Medical Center, both in Salt Lake City.

“It is essential to ask scleroderma patients questions in order to understand their gastrointestinal tract symptoms. The questionnaires are really critical for us to grade the severity and then properly order tests,” she explained. “The goal is symptom identification, ideally with minimal time burden and at no cost, to guide decisions that move our patients’ care forward.”

Three of the most useful validated instruments for assessment of GERD symptoms in scleroderma patients in routine clinical practice are the GerdQ, the University of California, Los Angeles, Scleroderma Clinical Trial Consortium GI Tract Questionnaire (UCLA GIT) 2.0 reflux scale, and the Patient-Reported Outcomes Measurement Information System (PROMIS) reflux scale.

The GerdQ is a six-item, self-administered questionnaire in which patients specify how many days in the past week they have experienced heartburn, regurgitation, nausea, sleep interference, upper abdominal pain, and need for medication. A free online tool is available for calculating the likelihood of having GERD based upon GerdQ score. A score of 8 or more points out of a possible 18 has the highest sensitivity and specificity for diagnosis of GERD.

The UCLA GIT 2.0 – the most commonly used instrument for GI symptom assessment in scleroderma patients – includes 34 items. It takes 6-8 minutes to complete the whole thing, but patients being assessed for GERD only need answer the eight GERD-specific questions. Six of these eight questions are the same as in the GerdQ. One of the two extra questions asks about difficulty in swallowing solid food, which if answered affirmatively warrants early referral to a gastroenterologist. The other question inquires about any food triggers for the reflux, providing an opportunity for a rheumatologist to educate the patient about the importance of avoiding acidic foods, such as tomatoes, and other food and drink generally considered healthy but which actually exacerbate GERD.

The National Institutes of Health PROMIS scale, the newest of the three instruments, is a 60-item questionnaire; however, only 20 questions relate to reflux and dysphagia and are thus germane to a focused GERD assessment in scleroderma.

When a clinical diagnosis of GERD is made in a scleroderma patient based upon symptoms elicited by questionnaire, guidelines recommend a trial of empiric proton pump inhibitor therapy and behavioral interventions, such as raising the head of the bed, in order to confirm the diagnosis. If the patient reports feeling better after these basic interventions, the diagnosis is confirmed. If not, it’s time to make a referral to a gastroenterologist for specialized care, Dr. Frech said.

Dr. Frech was a coinvestigator in an international, prospective, longitudinal study of patient-reported outcomes measures in 116 patients with scleroderma and GERD. All study participants had to complete the UCLA GIT 2.0, the PROMIS reflux scale, and a third patient-reported GERD measure both before and after the therapeutic intervention. The UCLA GIT 2.0 and PROMIS instruments demonstrated similarly robust sensitivity for identifying changes in GERD symptoms after therapeutic intervention.

“It doesn’t really matter what questionnaire we’re using,” according to the rheumatologist. “But I will point out that there is significant overlap in symptoms among GERD, gastroparesis, functional dyspepsia, and eosinophilic esophagitis, all of which cause symptoms of heartburn and regurgitation. So we don’t want to ask these questions just once, we want to make an intervention and then reask the questions to ensure that we’re continuously moving forward with the gastrointestinal tract management plan.”

Dr. Frech reported having no financial conflicts regarding her presentation.

bjancin@mdedge.com

A “growing and disturbing” increase in suicidal behavior among black youth has quietly been underway in the United States during the past several decades, even while rates in white and Latino youth have declined, Michael A. Lindsey, PhD, MSW, MPH, declared at the virtual annual meeting of the American Association of Suicidology.

Until recently this trend remained below the radar of public awareness. That’s changing. Dr. Lindsey was coauthor of a December 2019 report to Congress prepared in collaboration with the Congressional Black Caucus entitled, “Ring the Alarm: The Crisis of Black Youth Suicide In America.” Release of the report was accompanied by submission of an omnibus bill aimed at addressing the issue comprehensively, including what Dr. Lindsey considers to be the single most important policy imperative: providing federal resources to support more and better school mental health services proportionate to student needs.

“Black youth, relative to white youth, do not receive treatment for depression, which may be a precursor issue. They’re often disconnected from mental health therapy. This is perhaps a reason why we’re seeing this uptick in suicide expression among black youth,” according to Dr. Lindsey, executive director of the McSilver Institute for Poverty Policy and Research and professor of poverty studies at New York University.

Investigators at Ohio State University analyzed youth suicide data for the years 2001-2015 obtained from the Centers for Disease Control and Prevention. They determined that black children aged 5-12 years had an 82% higher incidence of completed suicide than white children (JAMA Pediatr. 2018 Jul 1;172[7]:697-9).

This report was followed by a study of trends in suicidal behaviors among U.S. high school students during 1991-2017. The study, led by Dr. Lindsey, used data from the Youth Risk Behavior Survey covering the years 1991-2017 to document an overall 19% prevalence of thoughts about suicide, while 15% of high school students had a suicide plan. During the study years there was a 73% increase in suicide attempts among black adolescents, while rates in white and Latino teens fell by 7.5% and 11.4%, respectively (Pediatrics. 2019 Nov;144[5]:e20191187).

Dr. Lindsey cited multiple reasons for undertreatment of depression in black youth. The lack of adequate mental health services in many schools figures prominently. As a result of this situation, mental health problems in black youth are often misinterpreted as conduct problems, leading to well-documented overuse of school suspensions and expulsions.

“We tend to oversuspend and expel black kids from school for problems that are treatable. This becomes a major, major issue in the pathway from schools to prisons,” he said.

Another factor in underutilization of mental health services by black youth is the stigma involved. Many black families see mental health therapy as irrelevant. Dr. Lindsey has received grant support from the National Institute of Mental Health for development of engagement interventions that focus on stigma reduction and enhancing family support for mental health therapy in black youth. He has found that, once those barriers are lowered, therapies seem to be as effective in black youth as in other populations, despite the cultural differences.

Yet another potential explanation for the racial disparity in pediatric suicide might be that suicide may, in some cases, be more of an impulsive behavior in black youth. Dr. Lindsey presented data from a soon-to-be-published analysis of Youth Risk Behavior Survey data on nearly 5,000 adolescents with suicidal thoughts, plans, and/or attempts within the previous 12 months. About 23% had suicidal thoughts only, 37% had suicidal thoughts and a plan, another 37% had thoughts, plans, and suicide attempts, and 3% had attempts without thoughts or a plan.

Black youth were 3.7 times more likely than white youth to have attempted suicide in the absence of background suicidal thoughts and 3.3 times more likely to have attempted suicide without having suicidal thoughts and plans.

He and his coinvestigators identified a similar pattern of suicide as an impulsive behavior in youths of all races with a history of sexual assault. They were 4.2 times more likely to have attempted suicide without prior suicidal thoughts than individuals without such a history and 3.9 times more likely to have attempted suicide without thinking about it or having a plan.

“This has implications for screening and prevention; warning signs may not be present,” he said.

Dr. Lindsey reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

A “growing and disturbing” increase in suicidal behavior among black youth has quietly been underway in the United States during the past several decades, even while rates in white and Latino youth have declined, Michael A. Lindsey, PhD, MSW, MPH, declared at the virtual annual meeting of the American Association of Suicidology.

Until recently this trend remained below the radar of public awareness. That’s changing. Dr. Lindsey was coauthor of a December 2019 report to Congress prepared in collaboration with the Congressional Black Caucus entitled, “Ring the Alarm: The Crisis of Black Youth Suicide In America.” Release of the report was accompanied by submission of an omnibus bill aimed at addressing the issue comprehensively, including what Dr. Lindsey considers to be the single most important policy imperative: providing federal resources to support more and better school mental health services proportionate to student needs.

“Black youth, relative to white youth, do not receive treatment for depression, which may be a precursor issue. They’re often disconnected from mental health therapy. This is perhaps a reason why we’re seeing this uptick in suicide expression among black youth,” according to Dr. Lindsey, executive director of the McSilver Institute for Poverty Policy and Research and professor of poverty studies at New York University.

Investigators at Ohio State University analyzed youth suicide data for the years 2001-2015 obtained from the Centers for Disease Control and Prevention. They determined that black children aged 5-12 years had an 82% higher incidence of completed suicide than white children (JAMA Pediatr. 2018 Jul 1;172[7]:697-9).

This report was followed by a study of trends in suicidal behaviors among U.S. high school students during 1991-2017. The study, led by Dr. Lindsey, used data from the Youth Risk Behavior Survey covering the years 1991-2017 to document an overall 19% prevalence of thoughts about suicide, while 15% of high school students had a suicide plan. During the study years there was a 73% increase in suicide attempts among black adolescents, while rates in white and Latino teens fell by 7.5% and 11.4%, respectively (Pediatrics. 2019 Nov;144[5]:e20191187).

Dr. Lindsey cited multiple reasons for undertreatment of depression in black youth. The lack of adequate mental health services in many schools figures prominently. As a result of this situation, mental health problems in black youth are often misinterpreted as conduct problems, leading to well-documented overuse of school suspensions and expulsions.

“We tend to oversuspend and expel black kids from school for problems that are treatable. This becomes a major, major issue in the pathway from schools to prisons,” he said.

Another factor in underutilization of mental health services by black youth is the stigma involved. Many black families see mental health therapy as irrelevant. Dr. Lindsey has received grant support from the National Institute of Mental Health for development of engagement interventions that focus on stigma reduction and enhancing family support for mental health therapy in black youth. He has found that, once those barriers are lowered, therapies seem to be as effective in black youth as in other populations, despite the cultural differences.

Yet another potential explanation for the racial disparity in pediatric suicide might be that suicide may, in some cases, be more of an impulsive behavior in black youth. Dr. Lindsey presented data from a soon-to-be-published analysis of Youth Risk Behavior Survey data on nearly 5,000 adolescents with suicidal thoughts, plans, and/or attempts within the previous 12 months. About 23% had suicidal thoughts only, 37% had suicidal thoughts and a plan, another 37% had thoughts, plans, and suicide attempts, and 3% had attempts without thoughts or a plan.

Black youth were 3.7 times more likely than white youth to have attempted suicide in the absence of background suicidal thoughts and 3.3 times more likely to have attempted suicide without having suicidal thoughts and plans.

He and his coinvestigators identified a similar pattern of suicide as an impulsive behavior in youths of all races with a history of sexual assault. They were 4.2 times more likely to have attempted suicide without prior suicidal thoughts than individuals without such a history and 3.9 times more likely to have attempted suicide without thinking about it or having a plan.

“This has implications for screening and prevention; warning signs may not be present,” he said.

Dr. Lindsey reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

A “growing and disturbing” increase in suicidal behavior among black youth has quietly been underway in the United States during the past several decades, even while rates in white and Latino youth have declined, Michael A. Lindsey, PhD, MSW, MPH, declared at the virtual annual meeting of the American Association of Suicidology.

Until recently this trend remained below the radar of public awareness. That’s changing. Dr. Lindsey was coauthor of a December 2019 report to Congress prepared in collaboration with the Congressional Black Caucus entitled, “Ring the Alarm: The Crisis of Black Youth Suicide In America.” Release of the report was accompanied by submission of an omnibus bill aimed at addressing the issue comprehensively, including what Dr. Lindsey considers to be the single most important policy imperative: providing federal resources to support more and better school mental health services proportionate to student needs.

“Black youth, relative to white youth, do not receive treatment for depression, which may be a precursor issue. They’re often disconnected from mental health therapy. This is perhaps a reason why we’re seeing this uptick in suicide expression among black youth,” according to Dr. Lindsey, executive director of the McSilver Institute for Poverty Policy and Research and professor of poverty studies at New York University.

Investigators at Ohio State University analyzed youth suicide data for the years 2001-2015 obtained from the Centers for Disease Control and Prevention. They determined that black children aged 5-12 years had an 82% higher incidence of completed suicide than white children (JAMA Pediatr. 2018 Jul 1;172[7]:697-9).

This report was followed by a study of trends in suicidal behaviors among U.S. high school students during 1991-2017. The study, led by Dr. Lindsey, used data from the Youth Risk Behavior Survey covering the years 1991-2017 to document an overall 19% prevalence of thoughts about suicide, while 15% of high school students had a suicide plan. During the study years there was a 73% increase in suicide attempts among black adolescents, while rates in white and Latino teens fell by 7.5% and 11.4%, respectively (Pediatrics. 2019 Nov;144[5]:e20191187).

Dr. Lindsey cited multiple reasons for undertreatment of depression in black youth. The lack of adequate mental health services in many schools figures prominently. As a result of this situation, mental health problems in black youth are often misinterpreted as conduct problems, leading to well-documented overuse of school suspensions and expulsions.

“We tend to oversuspend and expel black kids from school for problems that are treatable. This becomes a major, major issue in the pathway from schools to prisons,” he said.

Another factor in underutilization of mental health services by black youth is the stigma involved. Many black families see mental health therapy as irrelevant. Dr. Lindsey has received grant support from the National Institute of Mental Health for development of engagement interventions that focus on stigma reduction and enhancing family support for mental health therapy in black youth. He has found that, once those barriers are lowered, therapies seem to be as effective in black youth as in other populations, despite the cultural differences.

Yet another potential explanation for the racial disparity in pediatric suicide might be that suicide may, in some cases, be more of an impulsive behavior in black youth. Dr. Lindsey presented data from a soon-to-be-published analysis of Youth Risk Behavior Survey data on nearly 5,000 adolescents with suicidal thoughts, plans, and/or attempts within the previous 12 months. About 23% had suicidal thoughts only, 37% had suicidal thoughts and a plan, another 37% had thoughts, plans, and suicide attempts, and 3% had attempts without thoughts or a plan.

Black youth were 3.7 times more likely than white youth to have attempted suicide in the absence of background suicidal thoughts and 3.3 times more likely to have attempted suicide without having suicidal thoughts and plans.

He and his coinvestigators identified a similar pattern of suicide as an impulsive behavior in youths of all races with a history of sexual assault. They were 4.2 times more likely to have attempted suicide without prior suicidal thoughts than individuals without such a history and 3.9 times more likely to have attempted suicide without thinking about it or having a plan.

“This has implications for screening and prevention; warning signs may not be present,” he said.

Dr. Lindsey reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

The striking gains in functional capacity and quality of life conferred by baroreflex activation therapy in patients with heart failure, as shown in the pivotal phase 3 clinical trial for this novel intervention, were at least as great in women as in men, JoAnn Lindenfeld, MD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Mitchel L. Zoler/MDedge News

The results of the multicenter, prospective, randomized BeAT-HF trial led to marketing approval of the BaroStim Neo system for improvement in symptoms of heart failure with reduced ejection fraction (HFrEF) by the Food and Drug Administration in August 2019. Dr. Lindenfeld presented a fresh breakdown of the results by gender which showed, intriguingly, that the improvement in all study endpoints was consistently numerically greater in the women – sometimes startlingly so – although these gender differences in response didn’t achieve statistical significance. The 6-month randomized trial was underpowered for drawing definitive conclusions on that score, with a study population of only 53 women and 211 men. So the investigator remained circumspect.

“We think that what this study shows us is that women have at least equivalent improvement as men in this population. I don’t think we can conclude from this study yet that it’s better, but it’s certainly in all these parameters as least as good. And I think this is a population in which we’ve seen that improving symptoms and functional capacity is very important,” said Dr. Lindenfeld, professor of medicine and director of advanced heart failure/cardiac transplantation at Vanderbilt University, Nashville, Tenn.

The FDA approval was restricted to patients like those enrolled in BeAT-HF: that is, individuals with New York Heart Association functional class III heart failure, a left ventricular ejection fraction of 35% or less while on stable optimal medical therapy, and ineligibility for cardiac resynchronization therapy according to current guidelines. Seventy-eight percent of BeAT-HF participants had an implantable cardioverter-defibrillator.

Participants were randomized to baroreflex activation therapy (BAT) plus optimal medical therapy or to optimal medical therapy alone. The three coprimary endpoints were change from baseline to 6 months in 6-minute hall walk distance (6MHW), scores on the Minnesota Living with Heart Failure Questionnaire (MLHF), and N-terminal pro-B-type natriuretic peptide (NT-proBNP).

In the overall study population, 6MHW increased by 60 m in the BAT group and decreased by 8 m in controls; MLHF scores dropped by 14 and 6 points, respectively; and NT-proBNP fell by an average of 25% with BAT while rising by 3% in controls.

Very often, just a 5-point reduction in MLHF score is considered a clinically meaningful improvement in quality of life, the cardiologist noted.

The gender-based analysis is where things got particularly interesting.

The investigators defined a clinically relevant response as a greater than 10% increase from baseline on the 6MHW, at least a one-class improvement in NYHA class, or a reduction of 5 points or more on the MLHF. Among subjects in the BAT group, 70% of women and 60% of men met the clinically relevant response standard in terms of 6MHW, as did 70% of women and 64% of men for improvement in NYHA class, and 78% of women and 66% of men for MLHF score.

Eighty-seven percent of women and 68% of men on BAT had a clinically relevant response on at least one of these endpoints, as did about 28% of controls. Moreover, 31% of women in the BAT group were clinically relevant responders on at least two endpoints, compared with 19% of BAT men and 4% and 9% of controls.
 

Women dominate super-responder category

In order to be classified as a super responder, a patient had to demonstrate a greater than 20% increase in 6MHW, improvement in NYHA class I status, or at least a 10-point improvement in MLHF score. Ninety-one percent of women on BAT achieved super-responder status for at least one of these endpoints, compared with 76% of men. Forty-three percent of women and 24% of men in the BAT group were super responders in at least two domains, as were 8% and 11% of female and male controls, Dr. Lindenfeld continued.

Discussant Ewa Anita Jankowska, MD, PhD, deemed the BeAT-HF results on the therapeutic benefits of this autonomic modulation strategy “quite convincing.”

“We need to acknowledge that in recent years we have been spoiled a bit by the huge trials in heart failure where the ultimate goal was a reduction in mortality. But I think this is the time when we should think about the patients who want to live – here, now – with a better life. Patients expect symptomatic benefits. There is a substantial group of patients who are symptomatic even though they receive quite extensive neurohormonal blockage and who are not suitable for CRT. This study demonstrates that, for this group of patients, BAT can bring really significant symptomatic benefits,” she said.

“If you think about a treatment that provides patients who are NYHA class III an increase in 6MHW of 60 meters, that’s really something. And 20% of patients went from NYHA class III to class I – that’s really something, too,” added Dr. Jankowska, professor of medicine and head of the laboratory of applied research on the cardiovascular system at Wroclaw (Poland) University.

How baroreflex activation therapy works

The BaroStim system consists of a 2-mm unipolar electrode on a 7-mm backer that is placed over the carotid sinus. It is supported by a small generator with a 4- to 5-year battery life implanted under the collarbone, along with radiofrequency telemetry capability and programming flexibility.

Stimulation of the carotid baroreceptor promotes an integrated autonomic nervous system response which enhances parasympathetic activity and inhibits sympathetic nervous system activity. The result, as shown in numerous earlier proof-of-concept studies, is a reduced heart rate, decreased ventricular remodeling, enhanced diuresis, increased vasodilation, a drop in elevated blood pressure, and decreased renin secretion – all achieved nonpharmacologically.

The study was sponsored by CVRx. Dr. Lindenfeld reported serving as a consultant to CVRx, Abbott, AstraZeneca, Boehringer Ingelheim, Edwards Lifesciences, Impulse Dynamics, and VWave.

bjancin@mdedge.com

The striking gains in functional capacity and quality of life conferred by baroreflex activation therapy in patients with heart failure, as shown in the pivotal phase 3 clinical trial for this novel intervention, were at least as great in women as in men, JoAnn Lindenfeld, MD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Mitchel L. Zoler/MDedge News

The results of the multicenter, prospective, randomized BeAT-HF trial led to marketing approval of the BaroStim Neo system for improvement in symptoms of heart failure with reduced ejection fraction (HFrEF) by the Food and Drug Administration in August 2019. Dr. Lindenfeld presented a fresh breakdown of the results by gender which showed, intriguingly, that the improvement in all study endpoints was consistently numerically greater in the women – sometimes startlingly so – although these gender differences in response didn’t achieve statistical significance. The 6-month randomized trial was underpowered for drawing definitive conclusions on that score, with a study population of only 53 women and 211 men. So the investigator remained circumspect.

“We think that what this study shows us is that women have at least equivalent improvement as men in this population. I don’t think we can conclude from this study yet that it’s better, but it’s certainly in all these parameters as least as good. And I think this is a population in which we’ve seen that improving symptoms and functional capacity is very important,” said Dr. Lindenfeld, professor of medicine and director of advanced heart failure/cardiac transplantation at Vanderbilt University, Nashville, Tenn.

The FDA approval was restricted to patients like those enrolled in BeAT-HF: that is, individuals with New York Heart Association functional class III heart failure, a left ventricular ejection fraction of 35% or less while on stable optimal medical therapy, and ineligibility for cardiac resynchronization therapy according to current guidelines. Seventy-eight percent of BeAT-HF participants had an implantable cardioverter-defibrillator.

Participants were randomized to baroreflex activation therapy (BAT) plus optimal medical therapy or to optimal medical therapy alone. The three coprimary endpoints were change from baseline to 6 months in 6-minute hall walk distance (6MHW), scores on the Minnesota Living with Heart Failure Questionnaire (MLHF), and N-terminal pro-B-type natriuretic peptide (NT-proBNP).

In the overall study population, 6MHW increased by 60 m in the BAT group and decreased by 8 m in controls; MLHF scores dropped by 14 and 6 points, respectively; and NT-proBNP fell by an average of 25% with BAT while rising by 3% in controls.

Very often, just a 5-point reduction in MLHF score is considered a clinically meaningful improvement in quality of life, the cardiologist noted.

The gender-based analysis is where things got particularly interesting.

The investigators defined a clinically relevant response as a greater than 10% increase from baseline on the 6MHW, at least a one-class improvement in NYHA class, or a reduction of 5 points or more on the MLHF. Among subjects in the BAT group, 70% of women and 60% of men met the clinically relevant response standard in terms of 6MHW, as did 70% of women and 64% of men for improvement in NYHA class, and 78% of women and 66% of men for MLHF score.

Eighty-seven percent of women and 68% of men on BAT had a clinically relevant response on at least one of these endpoints, as did about 28% of controls. Moreover, 31% of women in the BAT group were clinically relevant responders on at least two endpoints, compared with 19% of BAT men and 4% and 9% of controls.
 

Women dominate super-responder category

In order to be classified as a super responder, a patient had to demonstrate a greater than 20% increase in 6MHW, improvement in NYHA class I status, or at least a 10-point improvement in MLHF score. Ninety-one percent of women on BAT achieved super-responder status for at least one of these endpoints, compared with 76% of men. Forty-three percent of women and 24% of men in the BAT group were super responders in at least two domains, as were 8% and 11% of female and male controls, Dr. Lindenfeld continued.

Discussant Ewa Anita Jankowska, MD, PhD, deemed the BeAT-HF results on the therapeutic benefits of this autonomic modulation strategy “quite convincing.”

“We need to acknowledge that in recent years we have been spoiled a bit by the huge trials in heart failure where the ultimate goal was a reduction in mortality. But I think this is the time when we should think about the patients who want to live – here, now – with a better life. Patients expect symptomatic benefits. There is a substantial group of patients who are symptomatic even though they receive quite extensive neurohormonal blockage and who are not suitable for CRT. This study demonstrates that, for this group of patients, BAT can bring really significant symptomatic benefits,” she said.

“If you think about a treatment that provides patients who are NYHA class III an increase in 6MHW of 60 meters, that’s really something. And 20% of patients went from NYHA class III to class I – that’s really something, too,” added Dr. Jankowska, professor of medicine and head of the laboratory of applied research on the cardiovascular system at Wroclaw (Poland) University.

How baroreflex activation therapy works

The BaroStim system consists of a 2-mm unipolar electrode on a 7-mm backer that is placed over the carotid sinus. It is supported by a small generator with a 4- to 5-year battery life implanted under the collarbone, along with radiofrequency telemetry capability and programming flexibility.

Stimulation of the carotid baroreceptor promotes an integrated autonomic nervous system response which enhances parasympathetic activity and inhibits sympathetic nervous system activity. The result, as shown in numerous earlier proof-of-concept studies, is a reduced heart rate, decreased ventricular remodeling, enhanced diuresis, increased vasodilation, a drop in elevated blood pressure, and decreased renin secretion – all achieved nonpharmacologically.

The study was sponsored by CVRx. Dr. Lindenfeld reported serving as a consultant to CVRx, Abbott, AstraZeneca, Boehringer Ingelheim, Edwards Lifesciences, Impulse Dynamics, and VWave.

bjancin@mdedge.com

The striking gains in functional capacity and quality of life conferred by baroreflex activation therapy in patients with heart failure, as shown in the pivotal phase 3 clinical trial for this novel intervention, were at least as great in women as in men, JoAnn Lindenfeld, MD, said at the European Society of Cardiology Heart Failure Discoveries virtual meeting.

Mitchel L. Zoler/MDedge News

The results of the multicenter, prospective, randomized BeAT-HF trial led to marketing approval of the BaroStim Neo system for improvement in symptoms of heart failure with reduced ejection fraction (HFrEF) by the Food and Drug Administration in August 2019. Dr. Lindenfeld presented a fresh breakdown of the results by gender which showed, intriguingly, that the improvement in all study endpoints was consistently numerically greater in the women – sometimes startlingly so – although these gender differences in response didn’t achieve statistical significance. The 6-month randomized trial was underpowered for drawing definitive conclusions on that score, with a study population of only 53 women and 211 men. So the investigator remained circumspect.

“We think that what this study shows us is that women have at least equivalent improvement as men in this population. I don’t think we can conclude from this study yet that it’s better, but it’s certainly in all these parameters as least as good. And I think this is a population in which we’ve seen that improving symptoms and functional capacity is very important,” said Dr. Lindenfeld, professor of medicine and director of advanced heart failure/cardiac transplantation at Vanderbilt University, Nashville, Tenn.

The FDA approval was restricted to patients like those enrolled in BeAT-HF: that is, individuals with New York Heart Association functional class III heart failure, a left ventricular ejection fraction of 35% or less while on stable optimal medical therapy, and ineligibility for cardiac resynchronization therapy according to current guidelines. Seventy-eight percent of BeAT-HF participants had an implantable cardioverter-defibrillator.

Participants were randomized to baroreflex activation therapy (BAT) plus optimal medical therapy or to optimal medical therapy alone. The three coprimary endpoints were change from baseline to 6 months in 6-minute hall walk distance (6MHW), scores on the Minnesota Living with Heart Failure Questionnaire (MLHF), and N-terminal pro-B-type natriuretic peptide (NT-proBNP).

In the overall study population, 6MHW increased by 60 m in the BAT group and decreased by 8 m in controls; MLHF scores dropped by 14 and 6 points, respectively; and NT-proBNP fell by an average of 25% with BAT while rising by 3% in controls.

Very often, just a 5-point reduction in MLHF score is considered a clinically meaningful improvement in quality of life, the cardiologist noted.

The gender-based analysis is where things got particularly interesting.

The investigators defined a clinically relevant response as a greater than 10% increase from baseline on the 6MHW, at least a one-class improvement in NYHA class, or a reduction of 5 points or more on the MLHF. Among subjects in the BAT group, 70% of women and 60% of men met the clinically relevant response standard in terms of 6MHW, as did 70% of women and 64% of men for improvement in NYHA class, and 78% of women and 66% of men for MLHF score.

Eighty-seven percent of women and 68% of men on BAT had a clinically relevant response on at least one of these endpoints, as did about 28% of controls. Moreover, 31% of women in the BAT group were clinically relevant responders on at least two endpoints, compared with 19% of BAT men and 4% and 9% of controls.
 

Women dominate super-responder category

In order to be classified as a super responder, a patient had to demonstrate a greater than 20% increase in 6MHW, improvement in NYHA class I status, or at least a 10-point improvement in MLHF score. Ninety-one percent of women on BAT achieved super-responder status for at least one of these endpoints, compared with 76% of men. Forty-three percent of women and 24% of men in the BAT group were super responders in at least two domains, as were 8% and 11% of female and male controls, Dr. Lindenfeld continued.

Discussant Ewa Anita Jankowska, MD, PhD, deemed the BeAT-HF results on the therapeutic benefits of this autonomic modulation strategy “quite convincing.”

“We need to acknowledge that in recent years we have been spoiled a bit by the huge trials in heart failure where the ultimate goal was a reduction in mortality. But I think this is the time when we should think about the patients who want to live – here, now – with a better life. Patients expect symptomatic benefits. There is a substantial group of patients who are symptomatic even though they receive quite extensive neurohormonal blockage and who are not suitable for CRT. This study demonstrates that, for this group of patients, BAT can bring really significant symptomatic benefits,” she said.

“If you think about a treatment that provides patients who are NYHA class III an increase in 6MHW of 60 meters, that’s really something. And 20% of patients went from NYHA class III to class I – that’s really something, too,” added Dr. Jankowska, professor of medicine and head of the laboratory of applied research on the cardiovascular system at Wroclaw (Poland) University.

How baroreflex activation therapy works

The BaroStim system consists of a 2-mm unipolar electrode on a 7-mm backer that is placed over the carotid sinus. It is supported by a small generator with a 4- to 5-year battery life implanted under the collarbone, along with radiofrequency telemetry capability and programming flexibility.

Stimulation of the carotid baroreceptor promotes an integrated autonomic nervous system response which enhances parasympathetic activity and inhibits sympathetic nervous system activity. The result, as shown in numerous earlier proof-of-concept studies, is a reduced heart rate, decreased ventricular remodeling, enhanced diuresis, increased vasodilation, a drop in elevated blood pressure, and decreased renin secretion – all achieved nonpharmacologically.

The study was sponsored by CVRx. Dr. Lindenfeld reported serving as a consultant to CVRx, Abbott, AstraZeneca, Boehringer Ingelheim, Edwards Lifesciences, Impulse Dynamics, and VWave.

bjancin@mdedge.com

The interleukin (IL)-23 inhibitor risankizumab was decisively more effective than the IL-17A inhibitor secukinumab at 52 weeks in a multinational randomized head-to-head trial in patients with moderate to severe psoriasis.

Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.

The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.

The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.

The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.

Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.

He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.

bjancin@mdedge.com

The interleukin (IL)-23 inhibitor risankizumab was decisively more effective than the IL-17A inhibitor secukinumab at 52 weeks in a multinational randomized head-to-head trial in patients with moderate to severe psoriasis.

Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.

The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.

The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.

The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.

Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.

He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.

bjancin@mdedge.com

The interleukin (IL)-23 inhibitor risankizumab was decisively more effective than the IL-17A inhibitor secukinumab at 52 weeks in a multinational randomized head-to-head trial in patients with moderate to severe psoriasis.

Risankizumab was better tolerated, with a significantly lower rate of treatment-emergent adverse events and a lower study dropout rate, Richard B. Warren, MBChB, PhD, reported at the virtual annual meeting of the American Academy of Dermatology.

In addition, the dosing schedule for risankizumab (Skyrizi) is more convenient, with maintenance dosing by subcutaneous injection once every 12 weeks, compared with monthly for secukinumab (Cosentyx), a biologic for psoriasis considered state-of-the-art not long ago, noted Dr. Warren, a dermatologist at the Salford (England) Royal NHS Foundation Trust and the Manchester NIHR Biomedical Research Center as well as professor of dermatology at the University of Manchester.

The phase 3 IMMERGE trial included 327 patients with moderate to severe psoriasis randomized to risankizumab or secukinumab for 52 weeks at their approved dosing. The trial, conducted mainly in the United States, Canada, and Europe, was open label, but evaluator blinded.

The coprimary endpoints were a 90% improvement from baseline in Psoriasis Area and Severity Index scores (PASI 90) at weeks 16 and 52. The week 52 PASI 90 response rates were 87% in the risankizumab group and 57% with secukinumab, for a highly significant absolute 30% difference. The week 16 result was a prespecified noninferiority analysis, and here again risankizumab met its mark, with a PASI 90 rate of 74%, statistically noninferior to the 66% rate with secukinumab, even though at that point patients had received only two doses of risankizumab, versus seven doses of secukinumab.

The PASI 100 response rate at 52 weeks, a key secondary endpoint, was 66% with risankizumab and 40% with secukinumab. Another secondary endpoint was achievement of a static Physician Global Assessment score of 0 or 1 – clear or almost clear – at week 52; the rates were 88% with risankizumab, 58% with secukinumab.

Ninety-two percent of participants randomized to risankizumab completed the full 52-week study, as did 82.8% of the secukinumab group. The nearly 10% absolute lower completion rate in the secukinumab group was driven by a higher rate of lack of efficacy – 4.3%, compared to 0.6% for risankizumab – and a greater incidence of adverse events. Indeed, treatment-emergent adverse events were fourfold more common in the secukinumab arm, with a rate of 4.9%, versus 1.2% with risankizumab, according to Dr. Warren.

He reported receiving research grants from and serving as a consultant to the study sponsor, AbbVie, as well as roughly a dozen other pharmaceutical companies.

bjancin@mdedge.com