User login
CPAP use associated with greater weight loss in obese patients with sleep apnea
NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.
“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.
Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.
In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.
“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.
“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.
Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.
According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.
“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.
“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.
“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”
SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.
NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.
“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.
Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.
In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.
“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.
“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.
Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.
According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.
“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.
“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.
“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”
SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.
NEW ORLEANS – Contrary to previously published data suggesting continuous positive airway pressure (CPAP) produces weight gain in patients with obstructive sleep apnea (OSA), new study findings presented at the annual meeting of the Endocrine Society provided data supporting the exact opposite conclusion.
“We think the data are strong enough to conclude that combining CPAP with a weight-loss program should be considered for all OSA patients. The weight-loss advantage is substantial,” reported Yuanjie Mao, MD, PhD, of the University of Arkansas for Medical Sciences, Little Rock.
Both weight loss and CPAP have been shown to be effective for the treatment of OSA, but concern that CPAP produces a counterproductive gain in weight was raised by findings in a meta-analysis in which CPAP was associated with increased body mass index (Thorax. 2015 Mar;70:258-64). As a result of that finding, some guidelines subsequently advised intensifying a weight-loss program at the time that CPAP is initiated to mitigate the weight gain effect, according to Dr. Mao. However, he noted that prospective data were never collected, so a causal relationship was never proven. Now, his data support the opposite conclusion.
In the more recent study, 300 patients who had participated in an intensive weight-loss program at his institution were divided into three groups: OSA patients who had been treated with CPAP, symptomatic OSA patients who had not been treated with CPAP, and asymptomatic OSA patients not treated with CPAP. They were compared retrospectively for weight change over a 16-week period.
“This was a very simple study,” said Dr. Mao, who explained that several exclusions, such as thyroid dysfunction, active infection, and uncontrolled diabetes, were used to reduce variables that might also affect weight change. At the end of 16 weeks, the median absolute weight loss in the CPAP group was 26.7 lb (12.1 kg), compared with 21 lb (9.5 kg) for the symptomatic OSA group and 19.2 lb (8.7 kg) for the asymptomatic OSA group. The weight loss was significantly greater for the CPAP group (P less than .01), compared with either of the other two groups, but not significantly different between the groups that were not treated with CPAP.
“The differences remained significant after adjusting for baseline BMI [body mass index], age, and gender,” Dr. Mao reported.
Asked why his data contradicted the previously reported data, Dr. Mao said that the previous studies were not evaluating CPAP in the context of a weight-loss program. He contends that when CPAP is combined with a rigorous weight-reduction regimen, there is an additive benefit from CPAP.
According to Dr. Mao, these data bring the value of CPAP for weight loss full circle. Before publication of the 2015 meta-analysis, it was widely assumed that CPAP helped with weight loss based on the expectation that better sleep quality would increase daytime activity. However, in the absence of strong data confirming that effect, Dr. Mao believes the unexpected results of the 2015 study easily pushed the pendulum in the opposite direction.
“The conclusion that CPAP increases weight was drawn from studies not designed to evaluate a weight-loss effect in those participating in a weight-loss program,” Dr. Mao explained. His study suggests that it is this combination that is important. He believes the observed effect from better sleep quality associated with CPAP is not necessarily related to better daytime function alone.
“Patients who sleep well also have more favorable diurnal changes in factors that might be important to weight change, such as leptin resistance and hormonal secretion,” he said. Although more work is needed to determine whether these purported mechanisms are important, he thinks his study has an immediate clinical message.
“Patients with OSA who are prescribed weight loss should also be considered for CPAP for the goal of weight loss,” Dr. Mao said. “We think this therapy should be started right away.”
SOURCE: Mao Y et al. ENDO 2019, Session SAT-095.
REPORTING FROM ENDO 2019
First RCT with aromatase inhibitor for male hypogonadism shows promise
NEW ORLEANS – In obese men with hypogonadotropic hypogonadism, an experimental aromatase inhibitor (Ai) normalized testosterone, seemed to improve sperm function, and was not associated with any significant adverse safety signals, according to findings presented at the annual meeting of the Endocrine Society.
Unlike testosterone therapy, “leflutrozole was associated with positive effects on semen fertility parameters, such as semen volume and concentration,” reported Thomas Hugh Jones, MD, FRCP, of the Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, and the department of oncology and metabolism, University of Sheffield Medical School, both in England.
Although the impact of the experimental aromatase inhibitor leflutrozole on parameters of semen function was an exploratory analysis in this multicenter, placebo-controlled study, it is particularly noteworthy because it addresses one of the weaknesses of testosterone replacement, which is often the first choice in treating hypogonadism, Dr. Jones said.
“Testosterone replacement frequently results in negative feedback suppression of follicle stimulating hormone and luteinizing hormone so that along with lower sperm counts, these men have significant problems with fertility,” he explained.
In this phase 2, double-blind, randomized trial, 271 men with hypogonadism were randomized to placebo or to leflutrozole in a dose of 0.1 mg, 0.3 mg, or 1.0 mg taken orally once weekly. All patients had a serum testosterone level of less than 300 ng/dL at entry. The median body mass index was 38 kg/m2, and the average age was 50.9 years.
Results were presented after 24 weeks of treatment, but the blinded study continued for an additional 24 weeks.
Normalization of testosterone, defined as a level between 300 and 1,000 ng/dL, was the primary endpoint. The mean testosterone levels were essentially unchanged in the placebo group during the first 24-week phase of the study, but they climbed to means of 458 ng/dL in the 0.1-mg group, 512 ng/dL in the 0.3-mg group, and 586 ng/dL in the 1.0-mg group.
“Overall, 75% were in the normal range, but it reached 90% in the groups taking the two higher doses,” Dr. Jones reported. Testosterone levels never exceeded 1,500 ng/d.
For the effect on FSH and LH, which were secondary endpoints, both were increased in a dose-dependent manner at 12 and 20 weeks (P less than .001 for the highest dose relative to placebo).
For the semen analysis, also conducted at 12 and 20 weeks, all three doses were associated with a numerical increase in sperm count relative to placebo, with the highest dose achieving significant improvements in semen volume (P = .006), semen concentration (P = .01), and total motile sperm count (P = .03), Dr. Jones reported.
“The 48-week analysis has just been completed, and these types of improvements have been persistent,” Dr. Jones said in reference to the increase in sex hormones as well as measures of sperm function. Although he did not present the 48-week results in detail, he disclosed that this longer follow-up also supported favorable effects on bone density, which is among several prespecified substudies being performed.
Leflutrozole, which is chemically related to letrozole, has been well tolerated at the doses studied. An increase in hematocrit consistent with the rise in testosterone was observed, but Dr. Jones reported that there are no significant safety issues identified so far.
Aromatase inhibitors have been used off label to treat hypogonadism, but this is the first randomized controlled trial for this indication, Dr. Jones said.
Although leflutrozole was used in this study at far lower doses than the aromatase inhibitors currently available for treatment of breast cancer, it might provide an advance for a challenging condition, according to Dr. Jones. He did not speculate when a phase 3 registration trial might start, but he did say that the promise of this agent warrants further development.
Dr. Jones reported a financial relationship with Mereo BioPharma, the sponsor of this trial.
Source: Jones et al. ENDO 2019, Session OR18-4.
NEW ORLEANS – In obese men with hypogonadotropic hypogonadism, an experimental aromatase inhibitor (Ai) normalized testosterone, seemed to improve sperm function, and was not associated with any significant adverse safety signals, according to findings presented at the annual meeting of the Endocrine Society.
Unlike testosterone therapy, “leflutrozole was associated with positive effects on semen fertility parameters, such as semen volume and concentration,” reported Thomas Hugh Jones, MD, FRCP, of the Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, and the department of oncology and metabolism, University of Sheffield Medical School, both in England.
Although the impact of the experimental aromatase inhibitor leflutrozole on parameters of semen function was an exploratory analysis in this multicenter, placebo-controlled study, it is particularly noteworthy because it addresses one of the weaknesses of testosterone replacement, which is often the first choice in treating hypogonadism, Dr. Jones said.
“Testosterone replacement frequently results in negative feedback suppression of follicle stimulating hormone and luteinizing hormone so that along with lower sperm counts, these men have significant problems with fertility,” he explained.
In this phase 2, double-blind, randomized trial, 271 men with hypogonadism were randomized to placebo or to leflutrozole in a dose of 0.1 mg, 0.3 mg, or 1.0 mg taken orally once weekly. All patients had a serum testosterone level of less than 300 ng/dL at entry. The median body mass index was 38 kg/m2, and the average age was 50.9 years.
Results were presented after 24 weeks of treatment, but the blinded study continued for an additional 24 weeks.
Normalization of testosterone, defined as a level between 300 and 1,000 ng/dL, was the primary endpoint. The mean testosterone levels were essentially unchanged in the placebo group during the first 24-week phase of the study, but they climbed to means of 458 ng/dL in the 0.1-mg group, 512 ng/dL in the 0.3-mg group, and 586 ng/dL in the 1.0-mg group.
“Overall, 75% were in the normal range, but it reached 90% in the groups taking the two higher doses,” Dr. Jones reported. Testosterone levels never exceeded 1,500 ng/d.
For the effect on FSH and LH, which were secondary endpoints, both were increased in a dose-dependent manner at 12 and 20 weeks (P less than .001 for the highest dose relative to placebo).
For the semen analysis, also conducted at 12 and 20 weeks, all three doses were associated with a numerical increase in sperm count relative to placebo, with the highest dose achieving significant improvements in semen volume (P = .006), semen concentration (P = .01), and total motile sperm count (P = .03), Dr. Jones reported.
“The 48-week analysis has just been completed, and these types of improvements have been persistent,” Dr. Jones said in reference to the increase in sex hormones as well as measures of sperm function. Although he did not present the 48-week results in detail, he disclosed that this longer follow-up also supported favorable effects on bone density, which is among several prespecified substudies being performed.
Leflutrozole, which is chemically related to letrozole, has been well tolerated at the doses studied. An increase in hematocrit consistent with the rise in testosterone was observed, but Dr. Jones reported that there are no significant safety issues identified so far.
Aromatase inhibitors have been used off label to treat hypogonadism, but this is the first randomized controlled trial for this indication, Dr. Jones said.
Although leflutrozole was used in this study at far lower doses than the aromatase inhibitors currently available for treatment of breast cancer, it might provide an advance for a challenging condition, according to Dr. Jones. He did not speculate when a phase 3 registration trial might start, but he did say that the promise of this agent warrants further development.
Dr. Jones reported a financial relationship with Mereo BioPharma, the sponsor of this trial.
Source: Jones et al. ENDO 2019, Session OR18-4.
NEW ORLEANS – In obese men with hypogonadotropic hypogonadism, an experimental aromatase inhibitor (Ai) normalized testosterone, seemed to improve sperm function, and was not associated with any significant adverse safety signals, according to findings presented at the annual meeting of the Endocrine Society.
Unlike testosterone therapy, “leflutrozole was associated with positive effects on semen fertility parameters, such as semen volume and concentration,” reported Thomas Hugh Jones, MD, FRCP, of the Centre for Diabetes and Endocrinology, Barnsley Hospital NHS Foundation Trust, and the department of oncology and metabolism, University of Sheffield Medical School, both in England.
Although the impact of the experimental aromatase inhibitor leflutrozole on parameters of semen function was an exploratory analysis in this multicenter, placebo-controlled study, it is particularly noteworthy because it addresses one of the weaknesses of testosterone replacement, which is often the first choice in treating hypogonadism, Dr. Jones said.
“Testosterone replacement frequently results in negative feedback suppression of follicle stimulating hormone and luteinizing hormone so that along with lower sperm counts, these men have significant problems with fertility,” he explained.
In this phase 2, double-blind, randomized trial, 271 men with hypogonadism were randomized to placebo or to leflutrozole in a dose of 0.1 mg, 0.3 mg, or 1.0 mg taken orally once weekly. All patients had a serum testosterone level of less than 300 ng/dL at entry. The median body mass index was 38 kg/m2, and the average age was 50.9 years.
Results were presented after 24 weeks of treatment, but the blinded study continued for an additional 24 weeks.
Normalization of testosterone, defined as a level between 300 and 1,000 ng/dL, was the primary endpoint. The mean testosterone levels were essentially unchanged in the placebo group during the first 24-week phase of the study, but they climbed to means of 458 ng/dL in the 0.1-mg group, 512 ng/dL in the 0.3-mg group, and 586 ng/dL in the 1.0-mg group.
“Overall, 75% were in the normal range, but it reached 90% in the groups taking the two higher doses,” Dr. Jones reported. Testosterone levels never exceeded 1,500 ng/d.
For the effect on FSH and LH, which were secondary endpoints, both were increased in a dose-dependent manner at 12 and 20 weeks (P less than .001 for the highest dose relative to placebo).
For the semen analysis, also conducted at 12 and 20 weeks, all three doses were associated with a numerical increase in sperm count relative to placebo, with the highest dose achieving significant improvements in semen volume (P = .006), semen concentration (P = .01), and total motile sperm count (P = .03), Dr. Jones reported.
“The 48-week analysis has just been completed, and these types of improvements have been persistent,” Dr. Jones said in reference to the increase in sex hormones as well as measures of sperm function. Although he did not present the 48-week results in detail, he disclosed that this longer follow-up also supported favorable effects on bone density, which is among several prespecified substudies being performed.
Leflutrozole, which is chemically related to letrozole, has been well tolerated at the doses studied. An increase in hematocrit consistent with the rise in testosterone was observed, but Dr. Jones reported that there are no significant safety issues identified so far.
Aromatase inhibitors have been used off label to treat hypogonadism, but this is the first randomized controlled trial for this indication, Dr. Jones said.
Although leflutrozole was used in this study at far lower doses than the aromatase inhibitors currently available for treatment of breast cancer, it might provide an advance for a challenging condition, according to Dr. Jones. He did not speculate when a phase 3 registration trial might start, but he did say that the promise of this agent warrants further development.
Dr. Jones reported a financial relationship with Mereo BioPharma, the sponsor of this trial.
Source: Jones et al. ENDO 2019, Session OR18-4.
REPORTING FROM ENDO 2019
New postmenopausal osteoporosis guidelines emphasize patient priorities
NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.
“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.
The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.
“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.
The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).
The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).
In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.
However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.
Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.
Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.
He reported having no relevant financial relationships.
NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.
“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.
The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.
“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.
The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).
The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).
In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.
However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.
Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.
Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.
He reported having no relevant financial relationships.
NEW ORLEANS – In new guidelines for the pharmacologic management of osteoporosis, bisphosphonates have been identified as the first-line therapy with denosumab (Prolia) listed as an acceptable alternative that is particularly well suited for high-risk patients, according to a presentation at the annual meeting of the Endocrine Society.
“We hope our guideline will not only improve patient care but provide confidence in treatment,” reported guideline writing committee member Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research at Maine Medical Center Research Institute, Scarborough.
The new guidelines are evidence based, relying on randomized, controlled trials to evaluate the data quality of treatment options with GRADE methodology, but Dr. Rosen said that the guideline writing committee also considered patient preferences because of concerns about the abundant evidence that adherence to pharmacologic therapies for osteoporosis is poor.
“There is a considerable gap in the treatment of osteoporosis. Most women will not take anti-osteoporosis therapies despite their efficacy, and those who do often stop,” Dr. Rosen observed. He said it was the intention of the writing committee to provide acceptable recommendations with a clear outline of benefits and risks in order to enlist patients more successfully in understanding and participating in fracture prevention.
The Endocrine Society guidelines, which are available online and will soon appear in print (J Clin Endocrinol Metab. 2019;104:1-28), are focused on pharmacologic management and therefore differ from guidelines on diagnosis and treatment published previously by the American Association of Clinical Endocrinologists (AACE) (Endocr Pract. 2016;22[Suppl 4]:1-42).
The AACE guidelines, which devote considerable space to prevention, indicated that bisphosphonates should “be generally considered as initial options for most patients who are candidates for treatment.” The AACE guidelines identify denosumab as the “treatment of choice” in patients with renal insufficiency (although not in those on dialysis or with end-stage renal disease).
In outlining some of the key features of the new guidelines at ENDO 2019, Dr. Rosen drew attention to a call for reevaluation of the need for bisphosphonates after patients have been on this therapy for 3 or more years. For those found at this time to be at low or moderate risk of fracture, a drug holiday is recommended based on guideline-cited evidence that bisphosphonates offer a residual therapeutic effect after stopping.
However, stopping is not recommended in those who remain at high risk. In these patients, bone density should be monitored at regular intervals for the goal of switching or intensifying therapy if needed. This includes use of teriparatide (Forteo) or abaloparatide (Tymlos) for periods of up to 2 years in patients with a history of severe or multiple fractures. These and other choices are included in a detailed algorithm covering both low- and high-risk patients.
Although many postmenopausal women hope to avoid pharmacologic therapy with high dietary intake of calcium and vitamin D, Dr. Rosen stressed the limited benefit of these nutrients in preventing fracture for those with established osteoporosis. While acknowledging that calcium and vitamin D enhance mineralization and maintenance of bone mass, he characterized them as “supplements” once pharmacologic therapies are indicated.
Unsurprisingly, patients prefer oral therapies that are effective but with a low burden of adverse events, according to a review of evidence undertaken by the guideline committee. Cost was a less important consideration. Dr. Rosen indicated that recognizing patient goals and priorities while explaining relative risks might engage patients in selecting a therapy to which they are willing to adhere.
He reported having no relevant financial relationships.
REPORTING FROM ENDO 2019
NIH director updates study enrolling one million participants
NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).
Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.
“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.
The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.
According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.
In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.
“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.
All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.
Information on enrollment is available on line: joinallofus.org.
NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).
Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.
“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.
The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.
According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.
In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.
“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.
All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.
Information on enrollment is available on line: joinallofus.org.
NEW ORLEANS – It is not too late to enroll your patients or yourself into the largest longitudinal cohort study ever initiated, according to Francis S. Collins, MD, PhD, who is director of the National Institutes of Health (NIH).
Since May 2018, when it was initiated, the NIH-funded All of Us Research Program has already enrolled 200,000 of the planned goal of one million participants in the United States. Of these, approximately half have already provided baseline demographics and health information as well as their consent to use the slew of health data that is being collected.
“The only way to do this kind of thing is to have data – a lot of it,” said Dr. Collins, explaining the premise of the All of Us Research Program in an interview conducted at the annual meeting of the Endocrine Society.
The data are not limited to medical records: Blood samples, whole genome sequencing, wearable activity monitors, and subject-completed questionnaires are among a long list of sources of information to be collected from participants, who are expected to be followed indefinitely.
According to Dr. Collins, who delivered a plenary address at the meeting, these data will become more valuable over time, one of the most important goals of this study is to prepare the way for precision medicine. As opposed to the traditional one-size-fits-all approach to treating disease, he believes that this large dataset will allow researchers to understand differences in common diseases at the individual level.
In relation to endocrinology, Dr. Collins said that a cohort of one million participants would be expected to have close to 100,000 individuals with diabetes mellitus.
“This is going to be transformative,” said Dr. Collins, who emphasized that the enrollment is specifically designed to capture participants from diverse ethnic and racial groups.
All of the data collected will be made broadly available to research initiatives of all kinds, many of which have not yet even been envisioned.
Information on enrollment is available on line: joinallofus.org.
REPORTING FROM ENDO 2019
Simple screening for risk of falling in elderly can guide prevention
NEW ORLEANS – , according to an update on this field at the annual meeting at the Endocrine Society.
“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.
There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.
“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.
Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.
As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.
In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.
Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.
There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.
Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.
“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.
Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.
Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.
Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.
Dr. Kaufman reported no relevant financial relationships to disclose.
NEW ORLEANS – , according to an update on this field at the annual meeting at the Endocrine Society.
“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.
There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.
“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.
Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.
As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.
In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.
Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.
There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.
Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.
“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.
Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.
Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.
Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.
Dr. Kaufman reported no relevant financial relationships to disclose.
NEW ORLEANS – , according to an update on this field at the annual meeting at the Endocrine Society.
“The risk of falling in older adults is very high, but risk can be evaluated, and there are effective strategies for risk reduction,” reported Kenton R. Kaufman, PhD, codirector of the Biomechanics and Motion Analysis Laboratory at the Mayo Clinic, Rochester, Minn.
There is not much debate that aging individuals are at an increased risk of falls, but Dr. Kaufman presented his own set of data to reinforce this point. In a longitudinal study of 125 individuals over the age of 65 years who were followed for a year at his institution, 59% had at least one fall even though all were healthy and functional when enrolled.
“It was more common to fall in summer than in winter, and most occurred on a level surface,” said Dr. Kaufman citing data from a study published 2 years ago (Arch Gerontol Geriatr. 2017;73:240-7). About half of the falls occurred at home.
Only 20%-30% of falls lead to moderate to severe injuries, but this is enough to make fall prevention an appropriate and important focus of public health initiatives to reduce morbidity and lower health costs, according to Dr. Kaufman, citing data suggesting that the medical costs total in the billions of dollars.
As a result of a substantial body of research in this area, there are now multiple clinical tests, such as grip strength, the functional reach test, and the 5-minute walk, that provide some degree of predictive value for identifying elderly individuals at risk for falls.
In addition, simple questionnaires that measure the fear of falling, such as the Activities-Specific Balance Confidence Scale (ABC test), and the Falls Efficacy Scale, also identify individuals at higher risk of falling. According to Dr. Kaufman, the predictive value of these questionnaires stems from the fact that those with more fears are more likely to fall.
Dr. Kaufman advised using these simple measures alone or in combination to screen aging patients for risk of failing. Although he singled out grip strength and the ABC test as the clinical test and the questionnaire he is most likely to employ, he believes others are also reasonable. When performed by primary care physicians, although not specialists, evaluating patients for risk of falling is Medicare-reimbursable, according to Dr. Kaufman.
There are two components to effective prophylaxis. One is improving muscle strength. The other is improving neuromuscular response, which means moving quickly enough to compensate when one’s center of gravity is disturbed. According to Dr. Kaufman, who cited two randomized trials, exercise to restore muscle strength can by itself reduce the risk of falling by 10%-20%.
Neuromuscular training is more intensive and not widely available but very effective. This involves training patients to improve their reaction time in the event of an impending fall. This approach, called postural perturbation training, employs a harness to prevent injury.
“The elderly can lose their facility for rapid recovery but this can be relearned,” said Dr. Kaufman, who cited another two randomized trials with this approach that reduced falls by 45% and 55%.
Postural perturbation training, although used to train amputees to gain comfort ambulating on artificial limbs, has so far had limited use in the elderly, but Dr. Kaufman said it might have utility in selected individuals, and he noted that there is at least one commercial device now being marketed.
Many elderly patients will not be candidates for training to reduce falls due to frailty or comorbid conditions that prevent exercise, but Dr. Kaufman encouraged clinicians to evaluate risk of falls in aging individuals who are active because there are strategies to reduce risk, and falls are a major source of morbidity and mortality.
Even for those who are not suitable for risk reduction strategies, testing for risk of falls has the ancillary benefit of raising awareness, according to Dr. Kaufman.
Dr. Kaufman reported no relevant financial relationships to disclose.
REPORTING FROM ENDO 2019
Real-world efficacy with intravascular lithotripsy
washington, dc – A real-world case series suggests intravascular lithotripsy (IVL) is safe and effective when used selectively to treat coronary arterial calcifications, according to data presented at the 2019 Transcatheter Cardiovascular Therapeutics (CRT) meeting.
Relative to other options, “IVL offers a more controlled means of calcium modification and it avoids the no-reflow phenomenon common to atherectomy in patients with a high calcium burden,” reported Julian Yeoh, MBBS, an interventional cardiologist affiliated with King’s College Hospital, London, UK.
On the basis of the DISRUPT CAD study, presented at the 2016 TCT meeting, IVL was approved in Europe for calcified coronary artery disease in May 2018. The Shockwave IVL device (Shockwave Medical) is currently approved in the U.S. only for treatment of calcified lesions associated with peripheral artery disease (PAD).
In what was characterized as a “real-world series,” 14 procedures were performed at Dr. Yeoh’s institution as part of a clinical study, but 40 procedures were completed on an all-comer basis. Many were performed for indications, such as multivessel disease, that would have been excluded from the DISRUPT CAD study.
“We included elderly patients, patients in cardiogenic shock, and patients with chronic total occlusions,” Dr. Yeoh reported. Presenting specific cases, he described using IVL to permit venous access for a transcatheter aortic valve replacement (TAVR), a failed rotational atherectomy, and to salvage a percutaneous angioplasty thwarted by residual calcium calcification.
“Total procedural success in this series was 91% with 100% facilitation of stent delivery,” Dr. Yeoh said. “There have been no cases of coronary perforation and no reflow or 30-day target lesion failure.”
In this series, the mean age of the patients was 75.9 years. On optical coherence tomography (OCT), which was employed in about half of the cases, the mean residual stenosis was approximately 20%.
IVL involves passing a balloon into the target lesion with the same guidewire used for other percutaneous interventions. Once in position, sonic pressure waves fracture the calcium deposit “with no injury to the intimal soft tissue,” according to Dr. Yeoh, who said that there were no serious adverse events associated with IVL in the series he presented.
In DISRUPT CAD, which enrolled 60 patients, procedural success was 95% with a reduction in mean stenosis from 68.1% to 13.1%. The rate of major adverse cardiovascular event (MACE) events was 5% at 30 days.
While DISRUPT CAD-II is an on-going post-market registry collecting data in Europe and other areas of the world where IVL is approved for treatment of coronary artery disease, a pivotal trial called DISRUPT CAD III has been launched to gain an indication for treatment of coronary calcifications in the U.S. The prospective global trial has a planned enrollment of nearly 400 patients with expected completion in August 2020.
SOURCE: Yeoh J et al. 2019 Cardiovascular Research Technologies (CRT) Meeting abstract.
washington, dc – A real-world case series suggests intravascular lithotripsy (IVL) is safe and effective when used selectively to treat coronary arterial calcifications, according to data presented at the 2019 Transcatheter Cardiovascular Therapeutics (CRT) meeting.
Relative to other options, “IVL offers a more controlled means of calcium modification and it avoids the no-reflow phenomenon common to atherectomy in patients with a high calcium burden,” reported Julian Yeoh, MBBS, an interventional cardiologist affiliated with King’s College Hospital, London, UK.
On the basis of the DISRUPT CAD study, presented at the 2016 TCT meeting, IVL was approved in Europe for calcified coronary artery disease in May 2018. The Shockwave IVL device (Shockwave Medical) is currently approved in the U.S. only for treatment of calcified lesions associated with peripheral artery disease (PAD).
In what was characterized as a “real-world series,” 14 procedures were performed at Dr. Yeoh’s institution as part of a clinical study, but 40 procedures were completed on an all-comer basis. Many were performed for indications, such as multivessel disease, that would have been excluded from the DISRUPT CAD study.
“We included elderly patients, patients in cardiogenic shock, and patients with chronic total occlusions,” Dr. Yeoh reported. Presenting specific cases, he described using IVL to permit venous access for a transcatheter aortic valve replacement (TAVR), a failed rotational atherectomy, and to salvage a percutaneous angioplasty thwarted by residual calcium calcification.
“Total procedural success in this series was 91% with 100% facilitation of stent delivery,” Dr. Yeoh said. “There have been no cases of coronary perforation and no reflow or 30-day target lesion failure.”
In this series, the mean age of the patients was 75.9 years. On optical coherence tomography (OCT), which was employed in about half of the cases, the mean residual stenosis was approximately 20%.
IVL involves passing a balloon into the target lesion with the same guidewire used for other percutaneous interventions. Once in position, sonic pressure waves fracture the calcium deposit “with no injury to the intimal soft tissue,” according to Dr. Yeoh, who said that there were no serious adverse events associated with IVL in the series he presented.
In DISRUPT CAD, which enrolled 60 patients, procedural success was 95% with a reduction in mean stenosis from 68.1% to 13.1%. The rate of major adverse cardiovascular event (MACE) events was 5% at 30 days.
While DISRUPT CAD-II is an on-going post-market registry collecting data in Europe and other areas of the world where IVL is approved for treatment of coronary artery disease, a pivotal trial called DISRUPT CAD III has been launched to gain an indication for treatment of coronary calcifications in the U.S. The prospective global trial has a planned enrollment of nearly 400 patients with expected completion in August 2020.
SOURCE: Yeoh J et al. 2019 Cardiovascular Research Technologies (CRT) Meeting abstract.
washington, dc – A real-world case series suggests intravascular lithotripsy (IVL) is safe and effective when used selectively to treat coronary arterial calcifications, according to data presented at the 2019 Transcatheter Cardiovascular Therapeutics (CRT) meeting.
Relative to other options, “IVL offers a more controlled means of calcium modification and it avoids the no-reflow phenomenon common to atherectomy in patients with a high calcium burden,” reported Julian Yeoh, MBBS, an interventional cardiologist affiliated with King’s College Hospital, London, UK.
On the basis of the DISRUPT CAD study, presented at the 2016 TCT meeting, IVL was approved in Europe for calcified coronary artery disease in May 2018. The Shockwave IVL device (Shockwave Medical) is currently approved in the U.S. only for treatment of calcified lesions associated with peripheral artery disease (PAD).
In what was characterized as a “real-world series,” 14 procedures were performed at Dr. Yeoh’s institution as part of a clinical study, but 40 procedures were completed on an all-comer basis. Many were performed for indications, such as multivessel disease, that would have been excluded from the DISRUPT CAD study.
“We included elderly patients, patients in cardiogenic shock, and patients with chronic total occlusions,” Dr. Yeoh reported. Presenting specific cases, he described using IVL to permit venous access for a transcatheter aortic valve replacement (TAVR), a failed rotational atherectomy, and to salvage a percutaneous angioplasty thwarted by residual calcium calcification.
“Total procedural success in this series was 91% with 100% facilitation of stent delivery,” Dr. Yeoh said. “There have been no cases of coronary perforation and no reflow or 30-day target lesion failure.”
In this series, the mean age of the patients was 75.9 years. On optical coherence tomography (OCT), which was employed in about half of the cases, the mean residual stenosis was approximately 20%.
IVL involves passing a balloon into the target lesion with the same guidewire used for other percutaneous interventions. Once in position, sonic pressure waves fracture the calcium deposit “with no injury to the intimal soft tissue,” according to Dr. Yeoh, who said that there were no serious adverse events associated with IVL in the series he presented.
In DISRUPT CAD, which enrolled 60 patients, procedural success was 95% with a reduction in mean stenosis from 68.1% to 13.1%. The rate of major adverse cardiovascular event (MACE) events was 5% at 30 days.
While DISRUPT CAD-II is an on-going post-market registry collecting data in Europe and other areas of the world where IVL is approved for treatment of coronary artery disease, a pivotal trial called DISRUPT CAD III has been launched to gain an indication for treatment of coronary calcifications in the U.S. The prospective global trial has a planned enrollment of nearly 400 patients with expected completion in August 2020.
SOURCE: Yeoh J et al. 2019 Cardiovascular Research Technologies (CRT) Meeting abstract.
REPORTING FROM CRT 2019
Endovascular device sustains blood pressure control after 3 years
WASHINGTON – As a result of remarkably sustained antihypertensive effect, interest is intensifying in the potential for a pivotal trial to associate a novel endovascular device with unprecedented blood pressure control in patients with treatment-resistant hypertension, according to an update presented at CRT 2019, sponsored by MedStar Heart & Vascular Institute.
With up to 3 years of follow-up, “systolic blood pressures have remained persistently reduced by as much as 24 mm Hg,” reported John P. Reilly, MD, an interventional cardiologist in Southampton, N.Y., who presented follow-up data for some of those enrolled in the first-in-human study of this device.
When the stent-like device is placed in the carotid artery, it alters its geometric shape, which increases pulsatile wall strain. The increase on wall strain alters an afferent signaling loop controlled by carotid baroreceptors that inhibits sympathetic outflow to lower blood pressure.
In the proof-of-principle, first-in-human CALM study, 47 patients were implanted with the device (MobiusHD, Vascular Dynamics). The initial study enrolled 30 subjects in Europe and 17 in the United States. Initial findings in the cohort of European patients, which included a mean 21–mm Hg reduction in systolic blood pressure and a 12–mm Hg reduction in diastolic blood pressure measured by ambulatory monitoring at 6 months, were published in the Lancet (2017 Dec 16;390[10113]:2655-661).
The patients enrolled in the proof-of-principle CALM trial were required to have highly-treatment-resistant hypertension, defined as a systolic blood pressure greater than or equal to 160 mm Hg despite at least three antihypertensive medications. The average number of medications was 4.4, according to Dr. Reilly. The mean blood pressure at entry was 165/98 mm Hg. Nearly 20% had previously undergone renal denervation.
The device was successfully deployed in all of the patients who participated in the open-label CALM study. Most of the 10 serious adverse events were related to hypotension, according to Dr. Reilly. Others included a wound infection and a case of intermittent claudication. Two instances of neurologic complaints, such as numbness and weakness, experienced within a day of device placement were considered potential transient ischemic attacks, but these resolved completely and no defects were observed on imaging.
In an update on CALM, Dr. Reilly reported that the large reductions in blood pressure previously reported at 6 months have been sustained. Follow-up is approximately 3 years in most patients, and the reductions previously reported have persisted in responders. When a clinically significant response is defined as a 10–mm Hg or more reduction in office blood pressure or 5–mm Hg or more reduction in ambulatory blood pressure, 75% of patients enrolled are still responding, but the more important point is that there has been no substantial reduction in blood pressure control over time in responders, according to Dr. Reilly.
When patients were stratified by a pulse pressure of greater or less than 70 mm Hg at study entry, response rates have been similar, he added.
The long-term responses are significant because there was concern about tachyphylaxis. In fact, coronary stents also produce a reduction in blood pressure immediately after placement that is likely caused by the same effect, but that effect “peters out in a day or 2,” noted Dr. Reilly. As opposed to the round shape of coronary stents, the rectangular shape of the novel device produces “an increase in the perceived strain on the carotid body” that does not appear to diminish over time.
CALM-2, which is designed to be a pivotal trial to support regulatory approval of the device, began enrolling in September 2018. An enrollment of 300 patients with treatment-resistant hypertension is planned. Participants will be randomized to receive the device or a sham procedure consisting of a carotid artery angiogram, according to Dr. Reilly. Although the initial CALM trial was small, open label, and conducted without a control, the persistent benefit over extended follow-up is driving excitement about the potential of this device.
“These are some of the greatest sustained reductions in ambulatory blood pressure we have ever seen,” according to Vasilios Papademetriou, MD, PhD, a professor of medicine at Georgetown University, Washington. Impressed by undiminished blood pressure control observed so far, he characterized the promise of this device as “very compelling.”
Dr. Reilly disclosed that he was a stockholder in Johnson & Johnson.
WASHINGTON – As a result of remarkably sustained antihypertensive effect, interest is intensifying in the potential for a pivotal trial to associate a novel endovascular device with unprecedented blood pressure control in patients with treatment-resistant hypertension, according to an update presented at CRT 2019, sponsored by MedStar Heart & Vascular Institute.
With up to 3 years of follow-up, “systolic blood pressures have remained persistently reduced by as much as 24 mm Hg,” reported John P. Reilly, MD, an interventional cardiologist in Southampton, N.Y., who presented follow-up data for some of those enrolled in the first-in-human study of this device.
When the stent-like device is placed in the carotid artery, it alters its geometric shape, which increases pulsatile wall strain. The increase on wall strain alters an afferent signaling loop controlled by carotid baroreceptors that inhibits sympathetic outflow to lower blood pressure.
In the proof-of-principle, first-in-human CALM study, 47 patients were implanted with the device (MobiusHD, Vascular Dynamics). The initial study enrolled 30 subjects in Europe and 17 in the United States. Initial findings in the cohort of European patients, which included a mean 21–mm Hg reduction in systolic blood pressure and a 12–mm Hg reduction in diastolic blood pressure measured by ambulatory monitoring at 6 months, were published in the Lancet (2017 Dec 16;390[10113]:2655-661).
The patients enrolled in the proof-of-principle CALM trial were required to have highly-treatment-resistant hypertension, defined as a systolic blood pressure greater than or equal to 160 mm Hg despite at least three antihypertensive medications. The average number of medications was 4.4, according to Dr. Reilly. The mean blood pressure at entry was 165/98 mm Hg. Nearly 20% had previously undergone renal denervation.
The device was successfully deployed in all of the patients who participated in the open-label CALM study. Most of the 10 serious adverse events were related to hypotension, according to Dr. Reilly. Others included a wound infection and a case of intermittent claudication. Two instances of neurologic complaints, such as numbness and weakness, experienced within a day of device placement were considered potential transient ischemic attacks, but these resolved completely and no defects were observed on imaging.
In an update on CALM, Dr. Reilly reported that the large reductions in blood pressure previously reported at 6 months have been sustained. Follow-up is approximately 3 years in most patients, and the reductions previously reported have persisted in responders. When a clinically significant response is defined as a 10–mm Hg or more reduction in office blood pressure or 5–mm Hg or more reduction in ambulatory blood pressure, 75% of patients enrolled are still responding, but the more important point is that there has been no substantial reduction in blood pressure control over time in responders, according to Dr. Reilly.
When patients were stratified by a pulse pressure of greater or less than 70 mm Hg at study entry, response rates have been similar, he added.
The long-term responses are significant because there was concern about tachyphylaxis. In fact, coronary stents also produce a reduction in blood pressure immediately after placement that is likely caused by the same effect, but that effect “peters out in a day or 2,” noted Dr. Reilly. As opposed to the round shape of coronary stents, the rectangular shape of the novel device produces “an increase in the perceived strain on the carotid body” that does not appear to diminish over time.
CALM-2, which is designed to be a pivotal trial to support regulatory approval of the device, began enrolling in September 2018. An enrollment of 300 patients with treatment-resistant hypertension is planned. Participants will be randomized to receive the device or a sham procedure consisting of a carotid artery angiogram, according to Dr. Reilly. Although the initial CALM trial was small, open label, and conducted without a control, the persistent benefit over extended follow-up is driving excitement about the potential of this device.
“These are some of the greatest sustained reductions in ambulatory blood pressure we have ever seen,” according to Vasilios Papademetriou, MD, PhD, a professor of medicine at Georgetown University, Washington. Impressed by undiminished blood pressure control observed so far, he characterized the promise of this device as “very compelling.”
Dr. Reilly disclosed that he was a stockholder in Johnson & Johnson.
WASHINGTON – As a result of remarkably sustained antihypertensive effect, interest is intensifying in the potential for a pivotal trial to associate a novel endovascular device with unprecedented blood pressure control in patients with treatment-resistant hypertension, according to an update presented at CRT 2019, sponsored by MedStar Heart & Vascular Institute.
With up to 3 years of follow-up, “systolic blood pressures have remained persistently reduced by as much as 24 mm Hg,” reported John P. Reilly, MD, an interventional cardiologist in Southampton, N.Y., who presented follow-up data for some of those enrolled in the first-in-human study of this device.
When the stent-like device is placed in the carotid artery, it alters its geometric shape, which increases pulsatile wall strain. The increase on wall strain alters an afferent signaling loop controlled by carotid baroreceptors that inhibits sympathetic outflow to lower blood pressure.
In the proof-of-principle, first-in-human CALM study, 47 patients were implanted with the device (MobiusHD, Vascular Dynamics). The initial study enrolled 30 subjects in Europe and 17 in the United States. Initial findings in the cohort of European patients, which included a mean 21–mm Hg reduction in systolic blood pressure and a 12–mm Hg reduction in diastolic blood pressure measured by ambulatory monitoring at 6 months, were published in the Lancet (2017 Dec 16;390[10113]:2655-661).
The patients enrolled in the proof-of-principle CALM trial were required to have highly-treatment-resistant hypertension, defined as a systolic blood pressure greater than or equal to 160 mm Hg despite at least three antihypertensive medications. The average number of medications was 4.4, according to Dr. Reilly. The mean blood pressure at entry was 165/98 mm Hg. Nearly 20% had previously undergone renal denervation.
The device was successfully deployed in all of the patients who participated in the open-label CALM study. Most of the 10 serious adverse events were related to hypotension, according to Dr. Reilly. Others included a wound infection and a case of intermittent claudication. Two instances of neurologic complaints, such as numbness and weakness, experienced within a day of device placement were considered potential transient ischemic attacks, but these resolved completely and no defects were observed on imaging.
In an update on CALM, Dr. Reilly reported that the large reductions in blood pressure previously reported at 6 months have been sustained. Follow-up is approximately 3 years in most patients, and the reductions previously reported have persisted in responders. When a clinically significant response is defined as a 10–mm Hg or more reduction in office blood pressure or 5–mm Hg or more reduction in ambulatory blood pressure, 75% of patients enrolled are still responding, but the more important point is that there has been no substantial reduction in blood pressure control over time in responders, according to Dr. Reilly.
When patients were stratified by a pulse pressure of greater or less than 70 mm Hg at study entry, response rates have been similar, he added.
The long-term responses are significant because there was concern about tachyphylaxis. In fact, coronary stents also produce a reduction in blood pressure immediately after placement that is likely caused by the same effect, but that effect “peters out in a day or 2,” noted Dr. Reilly. As opposed to the round shape of coronary stents, the rectangular shape of the novel device produces “an increase in the perceived strain on the carotid body” that does not appear to diminish over time.
CALM-2, which is designed to be a pivotal trial to support regulatory approval of the device, began enrolling in September 2018. An enrollment of 300 patients with treatment-resistant hypertension is planned. Participants will be randomized to receive the device or a sham procedure consisting of a carotid artery angiogram, according to Dr. Reilly. Although the initial CALM trial was small, open label, and conducted without a control, the persistent benefit over extended follow-up is driving excitement about the potential of this device.
“These are some of the greatest sustained reductions in ambulatory blood pressure we have ever seen,” according to Vasilios Papademetriou, MD, PhD, a professor of medicine at Georgetown University, Washington. Impressed by undiminished blood pressure control observed so far, he characterized the promise of this device as “very compelling.”
Dr. Reilly disclosed that he was a stockholder in Johnson & Johnson.
REPORTING FROM CRT 2019
Registry supports efficacy of coated balloon for peripheral artery stenosis
WASHINGTON – After patients with symptomatic peripheral arterial disease (PAD) were treated with a paclitaxel-coated balloon for 1 year, 89.5% remain free of target lesion restenosis (TLR), according to real-world registry data presented as a late-breaker at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
Freedom from TLR is the primary endpoint of this registry, which will continue to accrue data for 2 more years, according to Nicolas W. Shammas, MD, medical director of Midwest Cardiovascular Research Foundation, Davenport, Iowa.
The nearly 90% rate of freedom from TLR at 1 year was achieved “despite the fact that over 50% of the patients had diabetes, 29% had severe calcification, 35% had critical limb ischemia, and 25% had complete total occlusions,” said Dr. Shammas, an interventional cardiologist.
The registry, called SAFE-DCB, was created to evaluate long-term outcomes after treatment with the Lutonix (Bard Medical) paclitaxel-coated balloon catheter, which is employed in percutaneous angioplasty to treat stenotic lesions in the peripheral vasculature. Over an 18-month period, 1,005 patients were enrolled at 74 treatment centers. Dr. Shammas presented data on 766 of these patients, who have completed 12-months of follow-up. There are 835 patients enrolled in the ongoing study.
In a review of characteristics prior to treatment, Dr. Shammas reported that the average target lesion stenosis was 86.7% and the average target lesion length was 75 mm. Endovascular treatments prior to angioplasty were permitted in the registry protocol. Half of the patients underwent directional atherectomy.
After treatment, the residual stenosis was 11.54%. Even though the recommended protocol called for balloon inflations of 30 seconds each at a pressure of 7 atmospheres, the mean balloon inflation times were 35 seconds at 8 atmospheres. The mean total time for balloon inflations per patient was 152 seconds against the protocol recommendation of 140 seconds.
The primary safety endpoint was freedom from periprocedural mortality, limb amputation, and TLR at 30 days, which was achieved in 98.2% of patients.
Mortality at 1 year was 7.1%. Cardiovascular deaths, such as those due to myocardial infarction, were the most common, but there were noncardiovascular deaths, including those due to sepsis, respiratory failure, and kidney disease.
Women represented 43% of the study population. When compared with men, women achieved the primary outcome at a numerically lower rate, but the difference was not statistically significant. Dr. Shammas reported similar findings for those without complete total occlusions relative to those with complete total occlusions and those treated within the study protocol relative to those who were not. In each case, the differences in the proportion that achieved the primary outcome did not reach statistical significance.
Following his presentation, Dr. Shammas was asked to respond to the criticism that TLR is a soft endpoint. Since some proportion of patients might have had a return of symptoms due to restenosis but elected not to have a second procedure, TLR at 1 year is not equivalent to patency at 1 year.
While acknowledging the accuracy of this criticism, Dr. Shammas reported that TLR was a practical surrogate in the absence of imaging or another objective method of target lesion assessment. Noting that this endpoint has been employed before for long-term follow-up in trials of percutaneous therapies, he said that the TLR rates in this SAFE-DCB registry “are well within previously reported data” for 1-year outcomes with other treatments of symptomatic PAD.
SOURCE: Shammas N. CRT 2019 Mar 5.
WASHINGTON – After patients with symptomatic peripheral arterial disease (PAD) were treated with a paclitaxel-coated balloon for 1 year, 89.5% remain free of target lesion restenosis (TLR), according to real-world registry data presented as a late-breaker at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
Freedom from TLR is the primary endpoint of this registry, which will continue to accrue data for 2 more years, according to Nicolas W. Shammas, MD, medical director of Midwest Cardiovascular Research Foundation, Davenport, Iowa.
The nearly 90% rate of freedom from TLR at 1 year was achieved “despite the fact that over 50% of the patients had diabetes, 29% had severe calcification, 35% had critical limb ischemia, and 25% had complete total occlusions,” said Dr. Shammas, an interventional cardiologist.
The registry, called SAFE-DCB, was created to evaluate long-term outcomes after treatment with the Lutonix (Bard Medical) paclitaxel-coated balloon catheter, which is employed in percutaneous angioplasty to treat stenotic lesions in the peripheral vasculature. Over an 18-month period, 1,005 patients were enrolled at 74 treatment centers. Dr. Shammas presented data on 766 of these patients, who have completed 12-months of follow-up. There are 835 patients enrolled in the ongoing study.
In a review of characteristics prior to treatment, Dr. Shammas reported that the average target lesion stenosis was 86.7% and the average target lesion length was 75 mm. Endovascular treatments prior to angioplasty were permitted in the registry protocol. Half of the patients underwent directional atherectomy.
After treatment, the residual stenosis was 11.54%. Even though the recommended protocol called for balloon inflations of 30 seconds each at a pressure of 7 atmospheres, the mean balloon inflation times were 35 seconds at 8 atmospheres. The mean total time for balloon inflations per patient was 152 seconds against the protocol recommendation of 140 seconds.
The primary safety endpoint was freedom from periprocedural mortality, limb amputation, and TLR at 30 days, which was achieved in 98.2% of patients.
Mortality at 1 year was 7.1%. Cardiovascular deaths, such as those due to myocardial infarction, were the most common, but there were noncardiovascular deaths, including those due to sepsis, respiratory failure, and kidney disease.
Women represented 43% of the study population. When compared with men, women achieved the primary outcome at a numerically lower rate, but the difference was not statistically significant. Dr. Shammas reported similar findings for those without complete total occlusions relative to those with complete total occlusions and those treated within the study protocol relative to those who were not. In each case, the differences in the proportion that achieved the primary outcome did not reach statistical significance.
Following his presentation, Dr. Shammas was asked to respond to the criticism that TLR is a soft endpoint. Since some proportion of patients might have had a return of symptoms due to restenosis but elected not to have a second procedure, TLR at 1 year is not equivalent to patency at 1 year.
While acknowledging the accuracy of this criticism, Dr. Shammas reported that TLR was a practical surrogate in the absence of imaging or another objective method of target lesion assessment. Noting that this endpoint has been employed before for long-term follow-up in trials of percutaneous therapies, he said that the TLR rates in this SAFE-DCB registry “are well within previously reported data” for 1-year outcomes with other treatments of symptomatic PAD.
SOURCE: Shammas N. CRT 2019 Mar 5.
WASHINGTON – After patients with symptomatic peripheral arterial disease (PAD) were treated with a paclitaxel-coated balloon for 1 year, 89.5% remain free of target lesion restenosis (TLR), according to real-world registry data presented as a late-breaker at CRT 2019 sponsored by MedStar Heart & Vascular Institute.
Freedom from TLR is the primary endpoint of this registry, which will continue to accrue data for 2 more years, according to Nicolas W. Shammas, MD, medical director of Midwest Cardiovascular Research Foundation, Davenport, Iowa.
The nearly 90% rate of freedom from TLR at 1 year was achieved “despite the fact that over 50% of the patients had diabetes, 29% had severe calcification, 35% had critical limb ischemia, and 25% had complete total occlusions,” said Dr. Shammas, an interventional cardiologist.
The registry, called SAFE-DCB, was created to evaluate long-term outcomes after treatment with the Lutonix (Bard Medical) paclitaxel-coated balloon catheter, which is employed in percutaneous angioplasty to treat stenotic lesions in the peripheral vasculature. Over an 18-month period, 1,005 patients were enrolled at 74 treatment centers. Dr. Shammas presented data on 766 of these patients, who have completed 12-months of follow-up. There are 835 patients enrolled in the ongoing study.
In a review of characteristics prior to treatment, Dr. Shammas reported that the average target lesion stenosis was 86.7% and the average target lesion length was 75 mm. Endovascular treatments prior to angioplasty were permitted in the registry protocol. Half of the patients underwent directional atherectomy.
After treatment, the residual stenosis was 11.54%. Even though the recommended protocol called for balloon inflations of 30 seconds each at a pressure of 7 atmospheres, the mean balloon inflation times were 35 seconds at 8 atmospheres. The mean total time for balloon inflations per patient was 152 seconds against the protocol recommendation of 140 seconds.
The primary safety endpoint was freedom from periprocedural mortality, limb amputation, and TLR at 30 days, which was achieved in 98.2% of patients.
Mortality at 1 year was 7.1%. Cardiovascular deaths, such as those due to myocardial infarction, were the most common, but there were noncardiovascular deaths, including those due to sepsis, respiratory failure, and kidney disease.
Women represented 43% of the study population. When compared with men, women achieved the primary outcome at a numerically lower rate, but the difference was not statistically significant. Dr. Shammas reported similar findings for those without complete total occlusions relative to those with complete total occlusions and those treated within the study protocol relative to those who were not. In each case, the differences in the proportion that achieved the primary outcome did not reach statistical significance.
Following his presentation, Dr. Shammas was asked to respond to the criticism that TLR is a soft endpoint. Since some proportion of patients might have had a return of symptoms due to restenosis but elected not to have a second procedure, TLR at 1 year is not equivalent to patency at 1 year.
While acknowledging the accuracy of this criticism, Dr. Shammas reported that TLR was a practical surrogate in the absence of imaging or another objective method of target lesion assessment. Noting that this endpoint has been employed before for long-term follow-up in trials of percutaneous therapies, he said that the TLR rates in this SAFE-DCB registry “are well within previously reported data” for 1-year outcomes with other treatments of symptomatic PAD.
SOURCE: Shammas N. CRT 2019 Mar 5.
REPORTING FROM CRT 2019
Low Risk TAVR trial shows 3% mortality at 1 year
WASHINGTON –Anticipating two pivotal trials scheduled for presentation at the 2019 annual meeting of the American College of Cardiology (ACC), an investigator-led study of transaortic valve replacement (TAVR) for aortic stenosis presented as a latebreaker at 2019 CRT meeting produced excellent results.
Not least impressive, “our mortality rates are the lowest ever reported in any TAVR study at one year,” said Ronald Waksman, MD, Associate Director, Division of Cardiology, Medstar Heart Institute, Washington, DC.
In a population of patients with a median age of 71.1 years, all-cause mortality was just 3% at one year while the rate of deaths due to cardiovascular causes was only 1%, according to results of the 200-patient Low Risk TAVR study (LRT 1.0, NCT02628899) that Dr. Waksman presented.
In addition, there were low rates at one year for stroke (2.1%, none of which was deemed disability), myocardial infarction (1%), new onset atrial fibrillation (6.2%), and pacemaker placement (7.3%). The rate of rehospitalization for any cause was 20.4% but only 3.1% were considered related to TAVR. Rehospitalization for any cardiovascular cause at one year occurred in 6.8%.
Although leaflet thickening was observed at one year with imaging in 14%, this has not had any identifiable clinical consequences so far, and hemodynamics have remained stable, according to Dr. Waksman, who presented the interim 30-day outcomes at the 2018 CRT meeting.
These findings are raising expectations for two phase 3 TAVR trials in low-risk patients that are being presented as latebreakers at the 2019 ACC annual meeting. Both are large randomized trials comparing TAVR to surgical aortic valve replacement (SAVR) in low risk patients. Each trial is testing a single type of value and is funded by the valve manufacturers.
In the PARTNER-3 trial, patients randomized to TAVR received the Sapien 3 valve (Edwards Lifesciences). In the other latebreaking trial, patients randomized to TAVR received an Evolut valve (Medtronic Cardiovascular). Both are comparing TAVR to SAVR with a composite primary outcome that includes mortality and stroke measured at 30 days and one year.
In contrast to these trials, LRT 1.0 was conducted with no funding from a third party, according to Dr. Waksman. The eleven centers participated in the study at their own cost. Also, the choice of TAVR device was left to the discretion of the interventional cardiologist. Finally, most of the participating centers, although experienced in TAVR, did not have a high-volume case load. In general, with the exception of Dr. Waksman’s center, most performed 100 to 150 TAVRs per year.
“We were struck by the excellence of the performance of these sites,” said Dr. Waksman, noting that a comparison of outcomes at his center relative to the lower volume centers showed no significant differences in outcome.
This real-world experience raises the bar for the pivotal phase 3 trials, which, if positive, are expected to lead the FDA to grant an indication for TAVR in low-risk patients, according to Dr. Waksman. He announced that an LRT 2.0 trial, which will again include centers performing TAVRs at moderate volumes, is now enrolling.
SOURCE: 2019 Cardiovascular Research Technologies (CRT) Meeting.
WASHINGTON –Anticipating two pivotal trials scheduled for presentation at the 2019 annual meeting of the American College of Cardiology (ACC), an investigator-led study of transaortic valve replacement (TAVR) for aortic stenosis presented as a latebreaker at 2019 CRT meeting produced excellent results.
Not least impressive, “our mortality rates are the lowest ever reported in any TAVR study at one year,” said Ronald Waksman, MD, Associate Director, Division of Cardiology, Medstar Heart Institute, Washington, DC.
In a population of patients with a median age of 71.1 years, all-cause mortality was just 3% at one year while the rate of deaths due to cardiovascular causes was only 1%, according to results of the 200-patient Low Risk TAVR study (LRT 1.0, NCT02628899) that Dr. Waksman presented.
In addition, there were low rates at one year for stroke (2.1%, none of which was deemed disability), myocardial infarction (1%), new onset atrial fibrillation (6.2%), and pacemaker placement (7.3%). The rate of rehospitalization for any cause was 20.4% but only 3.1% were considered related to TAVR. Rehospitalization for any cardiovascular cause at one year occurred in 6.8%.
Although leaflet thickening was observed at one year with imaging in 14%, this has not had any identifiable clinical consequences so far, and hemodynamics have remained stable, according to Dr. Waksman, who presented the interim 30-day outcomes at the 2018 CRT meeting.
These findings are raising expectations for two phase 3 TAVR trials in low-risk patients that are being presented as latebreakers at the 2019 ACC annual meeting. Both are large randomized trials comparing TAVR to surgical aortic valve replacement (SAVR) in low risk patients. Each trial is testing a single type of value and is funded by the valve manufacturers.
In the PARTNER-3 trial, patients randomized to TAVR received the Sapien 3 valve (Edwards Lifesciences). In the other latebreaking trial, patients randomized to TAVR received an Evolut valve (Medtronic Cardiovascular). Both are comparing TAVR to SAVR with a composite primary outcome that includes mortality and stroke measured at 30 days and one year.
In contrast to these trials, LRT 1.0 was conducted with no funding from a third party, according to Dr. Waksman. The eleven centers participated in the study at their own cost. Also, the choice of TAVR device was left to the discretion of the interventional cardiologist. Finally, most of the participating centers, although experienced in TAVR, did not have a high-volume case load. In general, with the exception of Dr. Waksman’s center, most performed 100 to 150 TAVRs per year.
“We were struck by the excellence of the performance of these sites,” said Dr. Waksman, noting that a comparison of outcomes at his center relative to the lower volume centers showed no significant differences in outcome.
This real-world experience raises the bar for the pivotal phase 3 trials, which, if positive, are expected to lead the FDA to grant an indication for TAVR in low-risk patients, according to Dr. Waksman. He announced that an LRT 2.0 trial, which will again include centers performing TAVRs at moderate volumes, is now enrolling.
SOURCE: 2019 Cardiovascular Research Technologies (CRT) Meeting.
WASHINGTON –Anticipating two pivotal trials scheduled for presentation at the 2019 annual meeting of the American College of Cardiology (ACC), an investigator-led study of transaortic valve replacement (TAVR) for aortic stenosis presented as a latebreaker at 2019 CRT meeting produced excellent results.
Not least impressive, “our mortality rates are the lowest ever reported in any TAVR study at one year,” said Ronald Waksman, MD, Associate Director, Division of Cardiology, Medstar Heart Institute, Washington, DC.
In a population of patients with a median age of 71.1 years, all-cause mortality was just 3% at one year while the rate of deaths due to cardiovascular causes was only 1%, according to results of the 200-patient Low Risk TAVR study (LRT 1.0, NCT02628899) that Dr. Waksman presented.
In addition, there were low rates at one year for stroke (2.1%, none of which was deemed disability), myocardial infarction (1%), new onset atrial fibrillation (6.2%), and pacemaker placement (7.3%). The rate of rehospitalization for any cause was 20.4% but only 3.1% were considered related to TAVR. Rehospitalization for any cardiovascular cause at one year occurred in 6.8%.
Although leaflet thickening was observed at one year with imaging in 14%, this has not had any identifiable clinical consequences so far, and hemodynamics have remained stable, according to Dr. Waksman, who presented the interim 30-day outcomes at the 2018 CRT meeting.
These findings are raising expectations for two phase 3 TAVR trials in low-risk patients that are being presented as latebreakers at the 2019 ACC annual meeting. Both are large randomized trials comparing TAVR to surgical aortic valve replacement (SAVR) in low risk patients. Each trial is testing a single type of value and is funded by the valve manufacturers.
In the PARTNER-3 trial, patients randomized to TAVR received the Sapien 3 valve (Edwards Lifesciences). In the other latebreaking trial, patients randomized to TAVR received an Evolut valve (Medtronic Cardiovascular). Both are comparing TAVR to SAVR with a composite primary outcome that includes mortality and stroke measured at 30 days and one year.
In contrast to these trials, LRT 1.0 was conducted with no funding from a third party, according to Dr. Waksman. The eleven centers participated in the study at their own cost. Also, the choice of TAVR device was left to the discretion of the interventional cardiologist. Finally, most of the participating centers, although experienced in TAVR, did not have a high-volume case load. In general, with the exception of Dr. Waksman’s center, most performed 100 to 150 TAVRs per year.
“We were struck by the excellence of the performance of these sites,” said Dr. Waksman, noting that a comparison of outcomes at his center relative to the lower volume centers showed no significant differences in outcome.
This real-world experience raises the bar for the pivotal phase 3 trials, which, if positive, are expected to lead the FDA to grant an indication for TAVR in low-risk patients, according to Dr. Waksman. He announced that an LRT 2.0 trial, which will again include centers performing TAVRs at moderate volumes, is now enrolling.
SOURCE: 2019 Cardiovascular Research Technologies (CRT) Meeting.
REPORTING FROM CRT 2019
Alcohol-mediated renal denervation appears safe for BP reduction
WASHINGTON – Injection of dehydrated alcohol through the wall of the renal artery can be added to a growing list of renal denervation strategies that have been associated with sustained blood pressure reductions, according to data presented as a latebreaker at 2019 CRT meeting.
For the primary efficacy endpoint of change in systolic blood pressure at six months, the mean reduction six months after denervation was 11 mmHg as measured with 24-hour ambulatory blood pressure monitoring (ABPM), according to Horst Sievert, MD, PhD, Director of the CardioVascular Center, Frankfurt, Germany.
“Alcohol denervation was associated with efficient and safe lowering of systolic blood pressure,” reported Dr. Sievert, who said these data have prompted a new set of studies, including a phase 2 controlled trial that will evaluate the effect of renal denervation for control of blood pressure off-medication.
After consent was withdrawn from one patient, study results were available from 44 patients with treatment resistant hypertension who were enrolled in this initial study. Entry requirements included a mean systolic blood pressure greater than 150 mmHg while taking at least three antihypertensive medications from different classes.
In this study, the alcohol was delivered with a proprietary device called the Peregrine System™ infusion catheter (Ablation Solutions). This catheter is equipped with microneedles that remain retracted until the catheter is navigated into position. Once in the renal artery, the microneedles are deployed to inject alcohol into the perivascular space, which produces a neurolytic effect.
The technical success for delivery of the alcohol was achieved in 100% of the study group. There were no serious adverse events associated with treatment. Minor adverse events included those involving the access site, such as pain, as well as two dissections that resolved without treatment. One patient complained of abdominal pain on the day of the procedure, but that also resolved, according to Dr. Sievert.
Over the course of followup, patients remained on the therapies they were taking prior to the intervention. There was no change in antihypertensive therapy during the first month of followup in 84% of treated patients. Of those who did have a change in medication, all but one involved a reduction in medication prompted by improved blood pressure control. At six months, there was no change in medication for 73% of those evaluated.
Following alcohol denervation, there was a mean 7 mmHg reduction in diastolic pressure as measured with 24-hour ABBM.
Based on these data, a trials program is being launched. In addition to the phase 2 multinational off-medication trial, which is enrolling 300 patients who are being randomized to the alcohol denervation therapy or a sham control, an open-label crossover trial will be conducted to confirm the safety and tolerability of this approach.
Delivery of alcohol through the catheter device used in this study requires a renal artery diameter of at least 4 mm. This is a potential limitation for smaller individuals, but several other devices used for denervation share this requirement, according to Dr. Sievert.
The potential advantage of this approach is that “you can stay proximal,” according to Dr. Sievert, contrasting this technique with renal denervation by radiofrequency ablation. He explained that radiofrequency renal denervation requires a relatively distal approach to achieve an appropriate energy penetration for target nerve ablation. Further study is needed to determine whether more proximal delivery has any clinical advantage.
SOURCE: 2019 Cardiovascular Research Technologies (CRT) Meeting.
WASHINGTON – Injection of dehydrated alcohol through the wall of the renal artery can be added to a growing list of renal denervation strategies that have been associated with sustained blood pressure reductions, according to data presented as a latebreaker at 2019 CRT meeting.
For the primary efficacy endpoint of change in systolic blood pressure at six months, the mean reduction six months after denervation was 11 mmHg as measured with 24-hour ambulatory blood pressure monitoring (ABPM), according to Horst Sievert, MD, PhD, Director of the CardioVascular Center, Frankfurt, Germany.
“Alcohol denervation was associated with efficient and safe lowering of systolic blood pressure,” reported Dr. Sievert, who said these data have prompted a new set of studies, including a phase 2 controlled trial that will evaluate the effect of renal denervation for control of blood pressure off-medication.
After consent was withdrawn from one patient, study results were available from 44 patients with treatment resistant hypertension who were enrolled in this initial study. Entry requirements included a mean systolic blood pressure greater than 150 mmHg while taking at least three antihypertensive medications from different classes.
In this study, the alcohol was delivered with a proprietary device called the Peregrine System™ infusion catheter (Ablation Solutions). This catheter is equipped with microneedles that remain retracted until the catheter is navigated into position. Once in the renal artery, the microneedles are deployed to inject alcohol into the perivascular space, which produces a neurolytic effect.
The technical success for delivery of the alcohol was achieved in 100% of the study group. There were no serious adverse events associated with treatment. Minor adverse events included those involving the access site, such as pain, as well as two dissections that resolved without treatment. One patient complained of abdominal pain on the day of the procedure, but that also resolved, according to Dr. Sievert.
Over the course of followup, patients remained on the therapies they were taking prior to the intervention. There was no change in antihypertensive therapy during the first month of followup in 84% of treated patients. Of those who did have a change in medication, all but one involved a reduction in medication prompted by improved blood pressure control. At six months, there was no change in medication for 73% of those evaluated.
Following alcohol denervation, there was a mean 7 mmHg reduction in diastolic pressure as measured with 24-hour ABBM.
Based on these data, a trials program is being launched. In addition to the phase 2 multinational off-medication trial, which is enrolling 300 patients who are being randomized to the alcohol denervation therapy or a sham control, an open-label crossover trial will be conducted to confirm the safety and tolerability of this approach.
Delivery of alcohol through the catheter device used in this study requires a renal artery diameter of at least 4 mm. This is a potential limitation for smaller individuals, but several other devices used for denervation share this requirement, according to Dr. Sievert.
The potential advantage of this approach is that “you can stay proximal,” according to Dr. Sievert, contrasting this technique with renal denervation by radiofrequency ablation. He explained that radiofrequency renal denervation requires a relatively distal approach to achieve an appropriate energy penetration for target nerve ablation. Further study is needed to determine whether more proximal delivery has any clinical advantage.
SOURCE: 2019 Cardiovascular Research Technologies (CRT) Meeting.
WASHINGTON – Injection of dehydrated alcohol through the wall of the renal artery can be added to a growing list of renal denervation strategies that have been associated with sustained blood pressure reductions, according to data presented as a latebreaker at 2019 CRT meeting.
For the primary efficacy endpoint of change in systolic blood pressure at six months, the mean reduction six months after denervation was 11 mmHg as measured with 24-hour ambulatory blood pressure monitoring (ABPM), according to Horst Sievert, MD, PhD, Director of the CardioVascular Center, Frankfurt, Germany.
“Alcohol denervation was associated with efficient and safe lowering of systolic blood pressure,” reported Dr. Sievert, who said these data have prompted a new set of studies, including a phase 2 controlled trial that will evaluate the effect of renal denervation for control of blood pressure off-medication.
After consent was withdrawn from one patient, study results were available from 44 patients with treatment resistant hypertension who were enrolled in this initial study. Entry requirements included a mean systolic blood pressure greater than 150 mmHg while taking at least three antihypertensive medications from different classes.
In this study, the alcohol was delivered with a proprietary device called the Peregrine System™ infusion catheter (Ablation Solutions). This catheter is equipped with microneedles that remain retracted until the catheter is navigated into position. Once in the renal artery, the microneedles are deployed to inject alcohol into the perivascular space, which produces a neurolytic effect.
The technical success for delivery of the alcohol was achieved in 100% of the study group. There were no serious adverse events associated with treatment. Minor adverse events included those involving the access site, such as pain, as well as two dissections that resolved without treatment. One patient complained of abdominal pain on the day of the procedure, but that also resolved, according to Dr. Sievert.
Over the course of followup, patients remained on the therapies they were taking prior to the intervention. There was no change in antihypertensive therapy during the first month of followup in 84% of treated patients. Of those who did have a change in medication, all but one involved a reduction in medication prompted by improved blood pressure control. At six months, there was no change in medication for 73% of those evaluated.
Following alcohol denervation, there was a mean 7 mmHg reduction in diastolic pressure as measured with 24-hour ABBM.
Based on these data, a trials program is being launched. In addition to the phase 2 multinational off-medication trial, which is enrolling 300 patients who are being randomized to the alcohol denervation therapy or a sham control, an open-label crossover trial will be conducted to confirm the safety and tolerability of this approach.
Delivery of alcohol through the catheter device used in this study requires a renal artery diameter of at least 4 mm. This is a potential limitation for smaller individuals, but several other devices used for denervation share this requirement, according to Dr. Sievert.
The potential advantage of this approach is that “you can stay proximal,” according to Dr. Sievert, contrasting this technique with renal denervation by radiofrequency ablation. He explained that radiofrequency renal denervation requires a relatively distal approach to achieve an appropriate energy penetration for target nerve ablation. Further study is needed to determine whether more proximal delivery has any clinical advantage.
SOURCE: 2019 Cardiovascular Research Technologies (CRT) Meeting.
REPORTING FROM CRT 2019