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Should clinic BP be routinely measured lying down?
new preliminary research suggests.
An analysis of data from a long-running Atherosclerosis Risk in Communities (ARIC) study of more than 11,000 adults showed that those who had hypertension while supine were at elevated risk for cardiovascular disease (CVD) independently of their having hypertension while seated.
“If blood pressure is only measured while people are seated upright, cardiovascular disease risk may be missed if not measured also while they are lying supine on their backs,” lead investigator Duc M. Giao, a researcher and a fourth-year medical student at Harvard Medical School, Boston, said in a news release.
Mr. Giao presented the findings at the Hypertension Scientific Sessions.
Take seated and supine BP in clinic?
Hypertension while asleep is strongly associated with CVD and death, but whether hypertension detected in clinic while the patient is lying flat is a risk factor for CVD independently of the patient’s BP while seated remains unclear.
To investigate, Mr. Giao and colleagues reviewed health data for 11,369 adults (mean age, 54 years; 56% women; 25% Black persons) from the longitudinal ARIC study. None had a history of coronary heart disease (CHD), heart failure (HF), or stroke at baseline.
As part of the study, data on supine and seated BP were obtained during the enrollment period at ARIC visit 1, which took place between 1987 and 1989. Both seated and supine hypertension were defined as systolic BP ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg.
The data revealed that 16% of those without seated hypertension had supine hypertension, while 74% of those with seated hypertension had supine hypertension.
Despite adjusting for seated hypertension, during a median follow-up of 25-28 years, supine hypertension was associated with an increased risk for incident CHD (adjusted hazard ratio, 1.60; 95% confidence interval, 1.45-1.76), HF (aHR, 1.83; 95% CI, 1.68-2.01), stroke (aHR, 1.86; 95% CI, 1.63-2.13), fatal CHD (aHR, 2.18; 95% CI, 1.84-2.59), and all-cause mortality (aHR, 1.43; 95% CI, 1.35-1.52).
The results did not differ by antihypertensive medication use (P > .05).
For patients who had hypertension while supine but not while seated, elevations in risk were similar to those of peers who had hypertension while both seated and supine.
“Our findings suggest people with known risk factors for heart disease and stroke may benefit from having their blood pressure checked while lying flat on their backs,” Mr. Giao said in the conference news release.
“Efforts to manage blood pressure during daily life may help lower blood pressure while sleeping. Future research should compare supine blood pressure measurements in the clinic with overnight measurements,” Mr. Giao added.
Busy clinical practice
In a comment, Wanpen Vongpatanasin, MD, clinical chair for the conference, sponsored by the American Heart Association, said, “This finding highlights the importance of sustained control of BP in all body positions.”
She noted that many population-based studies have shown that nighttime BP independently predicts CV outcomes. “It’s unclear whether the timing of BP measurement (night vs. day) or the position (as most people sleep in supine position at night) explains this phenomenon.”
The study by Mr. Giao and colleagues suggests that “supine BP may be one explanation, as it has as much impact on long-term CV outcome as seated BP,” said Dr. Vongpatanasin, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center in Dallas.
However, “in busy clinical practice, it is impossible to do both seated and supine, as well as standing BP,” said Dr. Vongpatanasin.
“Additional studies are needed to determine what is considered to be the cutoff for normal supine BP and how to incorporate it in management of hypertension,” she added.
The study had no commercial funding. Mr. Giao and Dr. Vongpatanasin have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new preliminary research suggests.
An analysis of data from a long-running Atherosclerosis Risk in Communities (ARIC) study of more than 11,000 adults showed that those who had hypertension while supine were at elevated risk for cardiovascular disease (CVD) independently of their having hypertension while seated.
“If blood pressure is only measured while people are seated upright, cardiovascular disease risk may be missed if not measured also while they are lying supine on their backs,” lead investigator Duc M. Giao, a researcher and a fourth-year medical student at Harvard Medical School, Boston, said in a news release.
Mr. Giao presented the findings at the Hypertension Scientific Sessions.
Take seated and supine BP in clinic?
Hypertension while asleep is strongly associated with CVD and death, but whether hypertension detected in clinic while the patient is lying flat is a risk factor for CVD independently of the patient’s BP while seated remains unclear.
To investigate, Mr. Giao and colleagues reviewed health data for 11,369 adults (mean age, 54 years; 56% women; 25% Black persons) from the longitudinal ARIC study. None had a history of coronary heart disease (CHD), heart failure (HF), or stroke at baseline.
As part of the study, data on supine and seated BP were obtained during the enrollment period at ARIC visit 1, which took place between 1987 and 1989. Both seated and supine hypertension were defined as systolic BP ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg.
The data revealed that 16% of those without seated hypertension had supine hypertension, while 74% of those with seated hypertension had supine hypertension.
Despite adjusting for seated hypertension, during a median follow-up of 25-28 years, supine hypertension was associated with an increased risk for incident CHD (adjusted hazard ratio, 1.60; 95% confidence interval, 1.45-1.76), HF (aHR, 1.83; 95% CI, 1.68-2.01), stroke (aHR, 1.86; 95% CI, 1.63-2.13), fatal CHD (aHR, 2.18; 95% CI, 1.84-2.59), and all-cause mortality (aHR, 1.43; 95% CI, 1.35-1.52).
The results did not differ by antihypertensive medication use (P > .05).
For patients who had hypertension while supine but not while seated, elevations in risk were similar to those of peers who had hypertension while both seated and supine.
“Our findings suggest people with known risk factors for heart disease and stroke may benefit from having their blood pressure checked while lying flat on their backs,” Mr. Giao said in the conference news release.
“Efforts to manage blood pressure during daily life may help lower blood pressure while sleeping. Future research should compare supine blood pressure measurements in the clinic with overnight measurements,” Mr. Giao added.
Busy clinical practice
In a comment, Wanpen Vongpatanasin, MD, clinical chair for the conference, sponsored by the American Heart Association, said, “This finding highlights the importance of sustained control of BP in all body positions.”
She noted that many population-based studies have shown that nighttime BP independently predicts CV outcomes. “It’s unclear whether the timing of BP measurement (night vs. day) or the position (as most people sleep in supine position at night) explains this phenomenon.”
The study by Mr. Giao and colleagues suggests that “supine BP may be one explanation, as it has as much impact on long-term CV outcome as seated BP,” said Dr. Vongpatanasin, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center in Dallas.
However, “in busy clinical practice, it is impossible to do both seated and supine, as well as standing BP,” said Dr. Vongpatanasin.
“Additional studies are needed to determine what is considered to be the cutoff for normal supine BP and how to incorporate it in management of hypertension,” she added.
The study had no commercial funding. Mr. Giao and Dr. Vongpatanasin have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new preliminary research suggests.
An analysis of data from a long-running Atherosclerosis Risk in Communities (ARIC) study of more than 11,000 adults showed that those who had hypertension while supine were at elevated risk for cardiovascular disease (CVD) independently of their having hypertension while seated.
“If blood pressure is only measured while people are seated upright, cardiovascular disease risk may be missed if not measured also while they are lying supine on their backs,” lead investigator Duc M. Giao, a researcher and a fourth-year medical student at Harvard Medical School, Boston, said in a news release.
Mr. Giao presented the findings at the Hypertension Scientific Sessions.
Take seated and supine BP in clinic?
Hypertension while asleep is strongly associated with CVD and death, but whether hypertension detected in clinic while the patient is lying flat is a risk factor for CVD independently of the patient’s BP while seated remains unclear.
To investigate, Mr. Giao and colleagues reviewed health data for 11,369 adults (mean age, 54 years; 56% women; 25% Black persons) from the longitudinal ARIC study. None had a history of coronary heart disease (CHD), heart failure (HF), or stroke at baseline.
As part of the study, data on supine and seated BP were obtained during the enrollment period at ARIC visit 1, which took place between 1987 and 1989. Both seated and supine hypertension were defined as systolic BP ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg.
The data revealed that 16% of those without seated hypertension had supine hypertension, while 74% of those with seated hypertension had supine hypertension.
Despite adjusting for seated hypertension, during a median follow-up of 25-28 years, supine hypertension was associated with an increased risk for incident CHD (adjusted hazard ratio, 1.60; 95% confidence interval, 1.45-1.76), HF (aHR, 1.83; 95% CI, 1.68-2.01), stroke (aHR, 1.86; 95% CI, 1.63-2.13), fatal CHD (aHR, 2.18; 95% CI, 1.84-2.59), and all-cause mortality (aHR, 1.43; 95% CI, 1.35-1.52).
The results did not differ by antihypertensive medication use (P > .05).
For patients who had hypertension while supine but not while seated, elevations in risk were similar to those of peers who had hypertension while both seated and supine.
“Our findings suggest people with known risk factors for heart disease and stroke may benefit from having their blood pressure checked while lying flat on their backs,” Mr. Giao said in the conference news release.
“Efforts to manage blood pressure during daily life may help lower blood pressure while sleeping. Future research should compare supine blood pressure measurements in the clinic with overnight measurements,” Mr. Giao added.
Busy clinical practice
In a comment, Wanpen Vongpatanasin, MD, clinical chair for the conference, sponsored by the American Heart Association, said, “This finding highlights the importance of sustained control of BP in all body positions.”
She noted that many population-based studies have shown that nighttime BP independently predicts CV outcomes. “It’s unclear whether the timing of BP measurement (night vs. day) or the position (as most people sleep in supine position at night) explains this phenomenon.”
The study by Mr. Giao and colleagues suggests that “supine BP may be one explanation, as it has as much impact on long-term CV outcome as seated BP,” said Dr. Vongpatanasin, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center in Dallas.
However, “in busy clinical practice, it is impossible to do both seated and supine, as well as standing BP,” said Dr. Vongpatanasin.
“Additional studies are needed to determine what is considered to be the cutoff for normal supine BP and how to incorporate it in management of hypertension,” she added.
The study had no commercial funding. Mr. Giao and Dr. Vongpatanasin have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM HYPERTENSION 2023
Blood transfusions linked to intracerebral hemorrhage risk
In an exploratory analysis, patients receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs, and were assumed to have CAA, were at a significantly increased risk of developing spontaneous ICH themselves.
“This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of CAA might explain this association,” the investigators noted.
“We do not think that the findings motivate a change in practice, and we should not let these results discourage otherwise indicated blood transfusion,” said lead author Jingcheng Zhao, MD, PhD, with Karolinska University Hospital Solna, Stockholm.
The study was published online in the Journal of the American Medical Association.
Novel finding
Recent evidence suggests that CAA exhibits “prion-like” transmissivity, with reports of transmission through cadaveric pituitary hormone contaminated with amyloid-beta and tau protein, dura mater grafts, and possibly neurosurgical instruments.
CAA, which is characterized by the deposition of amyloid protein in the brain, is the second most common cause of spontaneous ICH.
The researchers hypothesized that transfusion transmission of CAA may manifest through an increased risk for spontaneous ICH among transfusion recipients given blood from a donor with spontaneous ICH. To explore this hypothesis, they analyzed national registry data from Sweden and Denmark for ICH in recipients of red blood cell transfusion from donors who themselves had ICH over the years after their blood donations, with the assumption that donors with two or more ICHs would likely have CAA.
The cohort included nearly 760,000 individuals in Sweden (median age, 65 years; 59% women) and 330,000 in Denmark (median age, 64 years; 58% women), with a median follow-up of 5.8 and 6.1 years, respectively.
Receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs was associated with a greater than twofold increased risk of developing spontaneous ICH, compared with receiving a transfusion from donors without subsequent ICH (hazard ratio, 2.73; P < .001 in the Swedish cohort and HR, 2.32; P = .04 in the Danish cohort).
“The observed increased risk of spontaneous ICH associated with receiving a red blood cell transfusion from a donor who later developed multiple spontaneous ICHs, corresponding to a 30-year cumulative incidence difference of 2.3%, is a novel finding,” the researchers wrote.
There was no increase in post-transfusion ICH risk among recipients whose donors had a single post–blood-donation ICH.
The findings were robust to several of the sensitivity analyses.
A “negative” control analysis of post-transfusion ischemic stroke (instead of ICH) found no increased risk among recipients of blood from donors who had single or multiple ICHs.
This study provides “exploratory evidence of possible transfusion-transmission of a factor that causes ICHs, but more research is needed to confirm and to understand the mechanism,” said Dr. Zhao.
The researchers noted that they did not directly assess CAA but expect it would be more common among donors who develop multiple spontaneous ICHs, “as CAA-related ICH has been reported to have a 7-fold increase for recurrent ICHs, compared with non–CAA-related ICH.”
Worrisome finding or false alarm?
In an accompanying editorial, Steven Greenberg, MD, PhD, with the department of neurology, Harvard Medical School, Boston, said there are “good reasons to treat the possibility of CAA transmission via blood transfusion seriously – and good reasons to remain skeptical, at least for the present.”
“Powerful” arguments in support of the findings include the robust study methodology and the “striking” similarity in results from the two registries, which argues against a chance finding. Another is the negative control with ischemic stroke as the outcome, which argues against unsuspected confounding-causing associations with all types of stroke, Dr. Greenberg noted.
Arguments for remaining “unconvinced” of the association center on the weakness of evidence for a plausible biological mechanism for the finding, he points out. Another is the short-time course of ICHs after blood transfusion, which is “quite challenging to explain,” Dr. Greenberg said. Nearly half of the ICHs among blood recipients occurred within 5 years of transfusion, which is “dramatically” faster than the 30- to 40-year interval reported between neurosurgical exposure to cadaveric tissue and first ICH, he added.
Another related “mechanistic reservation” is the plausibility that a transmissible species of amyloid-beta could travel from blood to brain in sufficient quantities to trigger advanced CAA or Alzheimer disease pathology, he wrote.
He added the current study leaves him “squarely at the corner of anxiety and skepticism.”
With more than 10 million units of blood transfused in the United States each year, even a modest increase in risk for future brain hemorrhages or dementia conferred by “an uncommon – but as of now undetectable – donor trait would represent a substantial public health concern,” Dr. Greenberg wrote.
“From the standpoint of scientific plausibility, however, even this well-conducted analysis is at risk of representing a false alarm,” he cautioned.
Looking ahead, Dr. Greenberg said one clear direction is independent replication, ideally with datasets in which donor and recipient dementia can be reliably ascertained to assess the possibility of Alzheimer’s disease as well as CAA transmissibility.
“The other challenge is for experimental biologists to consider the alternative possibility of transfusion-related acceleration of downstream steps in the CAA-ICH pathway, such as the vessel remodeling by which amyloid beta–laden vessels proceed to rupture and bleed.”
“The current study is not yet a reason for alarm, certainly not a reason to avoid otherwise indicated blood transfusion, but it is a strong call for more scientific digging,” Dr. Greenberg concluded.
The study was funded by grants from the Karolinska Institute, the Swedish Research Council, and Region Stockholm. Dr. Zhao and Dr. Greenberg report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In an exploratory analysis, patients receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs, and were assumed to have CAA, were at a significantly increased risk of developing spontaneous ICH themselves.
“This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of CAA might explain this association,” the investigators noted.
“We do not think that the findings motivate a change in practice, and we should not let these results discourage otherwise indicated blood transfusion,” said lead author Jingcheng Zhao, MD, PhD, with Karolinska University Hospital Solna, Stockholm.
The study was published online in the Journal of the American Medical Association.
Novel finding
Recent evidence suggests that CAA exhibits “prion-like” transmissivity, with reports of transmission through cadaveric pituitary hormone contaminated with amyloid-beta and tau protein, dura mater grafts, and possibly neurosurgical instruments.
CAA, which is characterized by the deposition of amyloid protein in the brain, is the second most common cause of spontaneous ICH.
The researchers hypothesized that transfusion transmission of CAA may manifest through an increased risk for spontaneous ICH among transfusion recipients given blood from a donor with spontaneous ICH. To explore this hypothesis, they analyzed national registry data from Sweden and Denmark for ICH in recipients of red blood cell transfusion from donors who themselves had ICH over the years after their blood donations, with the assumption that donors with two or more ICHs would likely have CAA.
The cohort included nearly 760,000 individuals in Sweden (median age, 65 years; 59% women) and 330,000 in Denmark (median age, 64 years; 58% women), with a median follow-up of 5.8 and 6.1 years, respectively.
Receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs was associated with a greater than twofold increased risk of developing spontaneous ICH, compared with receiving a transfusion from donors without subsequent ICH (hazard ratio, 2.73; P < .001 in the Swedish cohort and HR, 2.32; P = .04 in the Danish cohort).
“The observed increased risk of spontaneous ICH associated with receiving a red blood cell transfusion from a donor who later developed multiple spontaneous ICHs, corresponding to a 30-year cumulative incidence difference of 2.3%, is a novel finding,” the researchers wrote.
There was no increase in post-transfusion ICH risk among recipients whose donors had a single post–blood-donation ICH.
The findings were robust to several of the sensitivity analyses.
A “negative” control analysis of post-transfusion ischemic stroke (instead of ICH) found no increased risk among recipients of blood from donors who had single or multiple ICHs.
This study provides “exploratory evidence of possible transfusion-transmission of a factor that causes ICHs, but more research is needed to confirm and to understand the mechanism,” said Dr. Zhao.
The researchers noted that they did not directly assess CAA but expect it would be more common among donors who develop multiple spontaneous ICHs, “as CAA-related ICH has been reported to have a 7-fold increase for recurrent ICHs, compared with non–CAA-related ICH.”
Worrisome finding or false alarm?
In an accompanying editorial, Steven Greenberg, MD, PhD, with the department of neurology, Harvard Medical School, Boston, said there are “good reasons to treat the possibility of CAA transmission via blood transfusion seriously – and good reasons to remain skeptical, at least for the present.”
“Powerful” arguments in support of the findings include the robust study methodology and the “striking” similarity in results from the two registries, which argues against a chance finding. Another is the negative control with ischemic stroke as the outcome, which argues against unsuspected confounding-causing associations with all types of stroke, Dr. Greenberg noted.
Arguments for remaining “unconvinced” of the association center on the weakness of evidence for a plausible biological mechanism for the finding, he points out. Another is the short-time course of ICHs after blood transfusion, which is “quite challenging to explain,” Dr. Greenberg said. Nearly half of the ICHs among blood recipients occurred within 5 years of transfusion, which is “dramatically” faster than the 30- to 40-year interval reported between neurosurgical exposure to cadaveric tissue and first ICH, he added.
Another related “mechanistic reservation” is the plausibility that a transmissible species of amyloid-beta could travel from blood to brain in sufficient quantities to trigger advanced CAA or Alzheimer disease pathology, he wrote.
He added the current study leaves him “squarely at the corner of anxiety and skepticism.”
With more than 10 million units of blood transfused in the United States each year, even a modest increase in risk for future brain hemorrhages or dementia conferred by “an uncommon – but as of now undetectable – donor trait would represent a substantial public health concern,” Dr. Greenberg wrote.
“From the standpoint of scientific plausibility, however, even this well-conducted analysis is at risk of representing a false alarm,” he cautioned.
Looking ahead, Dr. Greenberg said one clear direction is independent replication, ideally with datasets in which donor and recipient dementia can be reliably ascertained to assess the possibility of Alzheimer’s disease as well as CAA transmissibility.
“The other challenge is for experimental biologists to consider the alternative possibility of transfusion-related acceleration of downstream steps in the CAA-ICH pathway, such as the vessel remodeling by which amyloid beta–laden vessels proceed to rupture and bleed.”
“The current study is not yet a reason for alarm, certainly not a reason to avoid otherwise indicated blood transfusion, but it is a strong call for more scientific digging,” Dr. Greenberg concluded.
The study was funded by grants from the Karolinska Institute, the Swedish Research Council, and Region Stockholm. Dr. Zhao and Dr. Greenberg report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In an exploratory analysis, patients receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs, and were assumed to have CAA, were at a significantly increased risk of developing spontaneous ICH themselves.
“This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of CAA might explain this association,” the investigators noted.
“We do not think that the findings motivate a change in practice, and we should not let these results discourage otherwise indicated blood transfusion,” said lead author Jingcheng Zhao, MD, PhD, with Karolinska University Hospital Solna, Stockholm.
The study was published online in the Journal of the American Medical Association.
Novel finding
Recent evidence suggests that CAA exhibits “prion-like” transmissivity, with reports of transmission through cadaveric pituitary hormone contaminated with amyloid-beta and tau protein, dura mater grafts, and possibly neurosurgical instruments.
CAA, which is characterized by the deposition of amyloid protein in the brain, is the second most common cause of spontaneous ICH.
The researchers hypothesized that transfusion transmission of CAA may manifest through an increased risk for spontaneous ICH among transfusion recipients given blood from a donor with spontaneous ICH. To explore this hypothesis, they analyzed national registry data from Sweden and Denmark for ICH in recipients of red blood cell transfusion from donors who themselves had ICH over the years after their blood donations, with the assumption that donors with two or more ICHs would likely have CAA.
The cohort included nearly 760,000 individuals in Sweden (median age, 65 years; 59% women) and 330,000 in Denmark (median age, 64 years; 58% women), with a median follow-up of 5.8 and 6.1 years, respectively.
Receiving red blood cell transfusions from donors who later developed multiple spontaneous ICHs was associated with a greater than twofold increased risk of developing spontaneous ICH, compared with receiving a transfusion from donors without subsequent ICH (hazard ratio, 2.73; P < .001 in the Swedish cohort and HR, 2.32; P = .04 in the Danish cohort).
“The observed increased risk of spontaneous ICH associated with receiving a red blood cell transfusion from a donor who later developed multiple spontaneous ICHs, corresponding to a 30-year cumulative incidence difference of 2.3%, is a novel finding,” the researchers wrote.
There was no increase in post-transfusion ICH risk among recipients whose donors had a single post–blood-donation ICH.
The findings were robust to several of the sensitivity analyses.
A “negative” control analysis of post-transfusion ischemic stroke (instead of ICH) found no increased risk among recipients of blood from donors who had single or multiple ICHs.
This study provides “exploratory evidence of possible transfusion-transmission of a factor that causes ICHs, but more research is needed to confirm and to understand the mechanism,” said Dr. Zhao.
The researchers noted that they did not directly assess CAA but expect it would be more common among donors who develop multiple spontaneous ICHs, “as CAA-related ICH has been reported to have a 7-fold increase for recurrent ICHs, compared with non–CAA-related ICH.”
Worrisome finding or false alarm?
In an accompanying editorial, Steven Greenberg, MD, PhD, with the department of neurology, Harvard Medical School, Boston, said there are “good reasons to treat the possibility of CAA transmission via blood transfusion seriously – and good reasons to remain skeptical, at least for the present.”
“Powerful” arguments in support of the findings include the robust study methodology and the “striking” similarity in results from the two registries, which argues against a chance finding. Another is the negative control with ischemic stroke as the outcome, which argues against unsuspected confounding-causing associations with all types of stroke, Dr. Greenberg noted.
Arguments for remaining “unconvinced” of the association center on the weakness of evidence for a plausible biological mechanism for the finding, he points out. Another is the short-time course of ICHs after blood transfusion, which is “quite challenging to explain,” Dr. Greenberg said. Nearly half of the ICHs among blood recipients occurred within 5 years of transfusion, which is “dramatically” faster than the 30- to 40-year interval reported between neurosurgical exposure to cadaveric tissue and first ICH, he added.
Another related “mechanistic reservation” is the plausibility that a transmissible species of amyloid-beta could travel from blood to brain in sufficient quantities to trigger advanced CAA or Alzheimer disease pathology, he wrote.
He added the current study leaves him “squarely at the corner of anxiety and skepticism.”
With more than 10 million units of blood transfused in the United States each year, even a modest increase in risk for future brain hemorrhages or dementia conferred by “an uncommon – but as of now undetectable – donor trait would represent a substantial public health concern,” Dr. Greenberg wrote.
“From the standpoint of scientific plausibility, however, even this well-conducted analysis is at risk of representing a false alarm,” he cautioned.
Looking ahead, Dr. Greenberg said one clear direction is independent replication, ideally with datasets in which donor and recipient dementia can be reliably ascertained to assess the possibility of Alzheimer’s disease as well as CAA transmissibility.
“The other challenge is for experimental biologists to consider the alternative possibility of transfusion-related acceleration of downstream steps in the CAA-ICH pathway, such as the vessel remodeling by which amyloid beta–laden vessels proceed to rupture and bleed.”
“The current study is not yet a reason for alarm, certainly not a reason to avoid otherwise indicated blood transfusion, but it is a strong call for more scientific digging,” Dr. Greenberg concluded.
The study was funded by grants from the Karolinska Institute, the Swedish Research Council, and Region Stockholm. Dr. Zhao and Dr. Greenberg report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
From JAMA
Patisiran (Onpattro) for ATTR cardiomyopathy gets FDA panel thumbs up
The Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration has voted 9 to 3 that the benefits of patisiran outweigh the risks for the treatment of ATTR amyloidosis cardiomyopathy – although many panel members questioned whether the benefits are clinically meaningful.
ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by misfolded TTR proteins, which accumulate as amyloid deposits in various parts of the body, including the heart.
Intravenously administered patisiran is already approved in the United States and Canada for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.
In the APOLLO-B trial, patisiran showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test, compared with placebo, in patients with ATTR amyloidosis with cardiomyopathy.
The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.
But in explaining her “no” vote, committee member C. Noel Bairey Merz, MD, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, said she “did not feel like there was benefit” using existing clinically relevant thresholds typically used in cardiology.
Committee chair Javed Butler, MD, MPH, Baylor Scott & White Research Institute, Dallas, who also voted no, said he “struggled” with this vote and emphasized that it “absolutely does not reflect that there is not a potential with the therapy.”
Dr. Butler said he voted no largely because he wasn’t sure whether the benefits are clinically meaningful in the context of the study design and how it was conducted. He did not have any safety concerns, which was the general feeling of the committee.
Edward Kasper, MD, Johns Hopkins University, Baltimore, who voted in favor of patisiran for ATTR amyloidosis with cardiomyopathy, said there is a “light wind for benefit and no wind for risk. So, if you’re asking do benefits outweigh the risks, the answer is yes.”
But Dr. Kasper also noted: “It would have been a more difficult question to answer: Is there clinically meaningful benefit versus risk? But that’s not what the question asked.”
In explaining his “yes” vote, Ravi Thadhani, MD, MPH, Emory University, Atlanta, said: “We’re dealing with a rare disease with few options and devastating consequences. We heard from clinicians loud and clear, and from patients for that matter, that options and alternatives are critical, and that there is a continuous decline of cardiac function and worsening of disease in a number of patients that have received the current standard of care. For me, the benefits outweigh the risks.”
Dr. Thadhani also noted that from the data provided, no benefit was shown – ”disappointingly” he lamented – for women, for Black persons, and among individuals who were receiving tafamidis, and he urged the FDA and sponsor to consider this.
The FDA has set a target action date for patisiran for ATTR amyloidosis cardiomyopathy of Oct. 8.
A version of this article first appeared on Medscape.com.
The Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration has voted 9 to 3 that the benefits of patisiran outweigh the risks for the treatment of ATTR amyloidosis cardiomyopathy – although many panel members questioned whether the benefits are clinically meaningful.
ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by misfolded TTR proteins, which accumulate as amyloid deposits in various parts of the body, including the heart.
Intravenously administered patisiran is already approved in the United States and Canada for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.
In the APOLLO-B trial, patisiran showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test, compared with placebo, in patients with ATTR amyloidosis with cardiomyopathy.
The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.
But in explaining her “no” vote, committee member C. Noel Bairey Merz, MD, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, said she “did not feel like there was benefit” using existing clinically relevant thresholds typically used in cardiology.
Committee chair Javed Butler, MD, MPH, Baylor Scott & White Research Institute, Dallas, who also voted no, said he “struggled” with this vote and emphasized that it “absolutely does not reflect that there is not a potential with the therapy.”
Dr. Butler said he voted no largely because he wasn’t sure whether the benefits are clinically meaningful in the context of the study design and how it was conducted. He did not have any safety concerns, which was the general feeling of the committee.
Edward Kasper, MD, Johns Hopkins University, Baltimore, who voted in favor of patisiran for ATTR amyloidosis with cardiomyopathy, said there is a “light wind for benefit and no wind for risk. So, if you’re asking do benefits outweigh the risks, the answer is yes.”
But Dr. Kasper also noted: “It would have been a more difficult question to answer: Is there clinically meaningful benefit versus risk? But that’s not what the question asked.”
In explaining his “yes” vote, Ravi Thadhani, MD, MPH, Emory University, Atlanta, said: “We’re dealing with a rare disease with few options and devastating consequences. We heard from clinicians loud and clear, and from patients for that matter, that options and alternatives are critical, and that there is a continuous decline of cardiac function and worsening of disease in a number of patients that have received the current standard of care. For me, the benefits outweigh the risks.”
Dr. Thadhani also noted that from the data provided, no benefit was shown – ”disappointingly” he lamented – for women, for Black persons, and among individuals who were receiving tafamidis, and he urged the FDA and sponsor to consider this.
The FDA has set a target action date for patisiran for ATTR amyloidosis cardiomyopathy of Oct. 8.
A version of this article first appeared on Medscape.com.
The Cardiovascular and Renal Drugs Advisory Committee of the Food and Drug Administration has voted 9 to 3 that the benefits of patisiran outweigh the risks for the treatment of ATTR amyloidosis cardiomyopathy – although many panel members questioned whether the benefits are clinically meaningful.
ATTR amyloidosis is an underdiagnosed, rapidly progressive, debilitating, and fatal disease caused by misfolded TTR proteins, which accumulate as amyloid deposits in various parts of the body, including the heart.
Intravenously administered patisiran is already approved in the United States and Canada for the treatment of the polyneuropathy of hereditary ATTR amyloidosis in adults.
In the APOLLO-B trial, patisiran showed a statistically significant and clinically meaningful benefit on functional capacity, as measured by the 6-minute walk test, compared with placebo, in patients with ATTR amyloidosis with cardiomyopathy.
The study also met its first secondary endpoint, demonstrating a statistically significant and clinically meaningful benefit on health status and quality of life.
But in explaining her “no” vote, committee member C. Noel Bairey Merz, MD, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, said she “did not feel like there was benefit” using existing clinically relevant thresholds typically used in cardiology.
Committee chair Javed Butler, MD, MPH, Baylor Scott & White Research Institute, Dallas, who also voted no, said he “struggled” with this vote and emphasized that it “absolutely does not reflect that there is not a potential with the therapy.”
Dr. Butler said he voted no largely because he wasn’t sure whether the benefits are clinically meaningful in the context of the study design and how it was conducted. He did not have any safety concerns, which was the general feeling of the committee.
Edward Kasper, MD, Johns Hopkins University, Baltimore, who voted in favor of patisiran for ATTR amyloidosis with cardiomyopathy, said there is a “light wind for benefit and no wind for risk. So, if you’re asking do benefits outweigh the risks, the answer is yes.”
But Dr. Kasper also noted: “It would have been a more difficult question to answer: Is there clinically meaningful benefit versus risk? But that’s not what the question asked.”
In explaining his “yes” vote, Ravi Thadhani, MD, MPH, Emory University, Atlanta, said: “We’re dealing with a rare disease with few options and devastating consequences. We heard from clinicians loud and clear, and from patients for that matter, that options and alternatives are critical, and that there is a continuous decline of cardiac function and worsening of disease in a number of patients that have received the current standard of care. For me, the benefits outweigh the risks.”
Dr. Thadhani also noted that from the data provided, no benefit was shown – ”disappointingly” he lamented – for women, for Black persons, and among individuals who were receiving tafamidis, and he urged the FDA and sponsor to consider this.
The FDA has set a target action date for patisiran for ATTR amyloidosis cardiomyopathy of Oct. 8.
A version of this article first appeared on Medscape.com.
Cold weather may challenge blood pressure control
A review of electronic health records of more than 60,000 U.S. adults being treated for hypertension found that on average, systolic BP rose by up to 1.7 mm Hg in the cold winter months, compared with the hot summer months.
On a population level, BP control rates decreased by up to 5% during the cold winter months, compared with control rates in the warm summer months.
“Some patients may benefit from increased pharmacological intervention to keep blood pressure controlled during the winter,” Robert Barrett, with the American Medical Association, Greenville, S.C., told this news organization.
“Individuals with hypertension or values near the range of hypertension may benefit from periodic blood pressure monitoring and improvements in physical activity and nutritional patterns during winter months to offset adverse effects from seasonal blood pressure changes,” Mr. Barrett added in a news release.
Mr. Barrett presented the study findings at the American Heart Association Hypertension Scientific Sessions 2023 in Boston.
Supportive data
Mr. Barrett explained that seasonal variation in BP has been previously documented, and as part of the evaluation for the AMA MAP Hypertension program, he and colleagues were interested in the effect of this variation on population control rates under standard metrics (visits with BP < 140/90 mm Hg).
They analyzed data from 60,676 men and women (mean age, 62 years) with hypertension from six health care organizations in the southeastern and midwestern United States that were participating in the quality improvement program.
During the roughly 5-year assessment period, none of the patients had changes in their antihypertensive medication, and all had at least one visit in each temperate season. The researchers estimated the seasonal effect on average systolic BP and BP control (defined as < 140/90 mm Hg).
Across a total of 453,787 visits, systolic BP during the winter averaged 0.47 mm Hg higher (95% confidence interval, 0.364-0.573) than the yearly average, with a significantly lower odds ratio for BP control (OR, 0.92; 95% CI, 0.91-0.94), the researchers report.
In contrast, average systolic BP was 0.92 mm Hg lower during the summer, with a higher likelihood of BP control (OR ,1.10; 95% CI, 1.07-1.12).
“Seasonal variation in blood pressure has a substantial effect on hypertension control, often defined as blood pressure < 140/90,” Barrett told this news organization.
“Patients with hypertension are less likely to have their blood pressure controlled during winter than summer months. If the blood pressure is very well controlled, for example to < 130/80, then seasonal variation will have little effect on control to < 140/90,” Mr. Barrett noted.
“However, if blood pressure is not well controlled, then patients near the 140/90 level could benefit from monitoring their blood pressure regularly, closer medical follow-up, and avoiding decreased physical activity and increased weight toward year end,” he added.
Wanpen Vongpatanasin, MD, clinical chair for the conference, said that it’s “well known that BP tends to lower during summer months and patients may be susceptible to dehydration and acute kidney injury when BP is too low, particularly when treated with certain medication such as diuretics.”
On the flip side, “cold weather predisposes to vasoconstriction as our blood vessel constrict to maintain core temperature and it could be challenging to manage BP. That’s why it is important for high BP patients to monitor home BP regularly,” said Dr. Vongpatanasin, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center, Dallas.
The study had no commercial funding. Mr. Barrett and Dr. Vongpatanasin have no relevant disclosures.
A version of this article first appeared on Medscape.com.
A review of electronic health records of more than 60,000 U.S. adults being treated for hypertension found that on average, systolic BP rose by up to 1.7 mm Hg in the cold winter months, compared with the hot summer months.
On a population level, BP control rates decreased by up to 5% during the cold winter months, compared with control rates in the warm summer months.
“Some patients may benefit from increased pharmacological intervention to keep blood pressure controlled during the winter,” Robert Barrett, with the American Medical Association, Greenville, S.C., told this news organization.
“Individuals with hypertension or values near the range of hypertension may benefit from periodic blood pressure monitoring and improvements in physical activity and nutritional patterns during winter months to offset adverse effects from seasonal blood pressure changes,” Mr. Barrett added in a news release.
Mr. Barrett presented the study findings at the American Heart Association Hypertension Scientific Sessions 2023 in Boston.
Supportive data
Mr. Barrett explained that seasonal variation in BP has been previously documented, and as part of the evaluation for the AMA MAP Hypertension program, he and colleagues were interested in the effect of this variation on population control rates under standard metrics (visits with BP < 140/90 mm Hg).
They analyzed data from 60,676 men and women (mean age, 62 years) with hypertension from six health care organizations in the southeastern and midwestern United States that were participating in the quality improvement program.
During the roughly 5-year assessment period, none of the patients had changes in their antihypertensive medication, and all had at least one visit in each temperate season. The researchers estimated the seasonal effect on average systolic BP and BP control (defined as < 140/90 mm Hg).
Across a total of 453,787 visits, systolic BP during the winter averaged 0.47 mm Hg higher (95% confidence interval, 0.364-0.573) than the yearly average, with a significantly lower odds ratio for BP control (OR, 0.92; 95% CI, 0.91-0.94), the researchers report.
In contrast, average systolic BP was 0.92 mm Hg lower during the summer, with a higher likelihood of BP control (OR ,1.10; 95% CI, 1.07-1.12).
“Seasonal variation in blood pressure has a substantial effect on hypertension control, often defined as blood pressure < 140/90,” Barrett told this news organization.
“Patients with hypertension are less likely to have their blood pressure controlled during winter than summer months. If the blood pressure is very well controlled, for example to < 130/80, then seasonal variation will have little effect on control to < 140/90,” Mr. Barrett noted.
“However, if blood pressure is not well controlled, then patients near the 140/90 level could benefit from monitoring their blood pressure regularly, closer medical follow-up, and avoiding decreased physical activity and increased weight toward year end,” he added.
Wanpen Vongpatanasin, MD, clinical chair for the conference, said that it’s “well known that BP tends to lower during summer months and patients may be susceptible to dehydration and acute kidney injury when BP is too low, particularly when treated with certain medication such as diuretics.”
On the flip side, “cold weather predisposes to vasoconstriction as our blood vessel constrict to maintain core temperature and it could be challenging to manage BP. That’s why it is important for high BP patients to monitor home BP regularly,” said Dr. Vongpatanasin, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center, Dallas.
The study had no commercial funding. Mr. Barrett and Dr. Vongpatanasin have no relevant disclosures.
A version of this article first appeared on Medscape.com.
A review of electronic health records of more than 60,000 U.S. adults being treated for hypertension found that on average, systolic BP rose by up to 1.7 mm Hg in the cold winter months, compared with the hot summer months.
On a population level, BP control rates decreased by up to 5% during the cold winter months, compared with control rates in the warm summer months.
“Some patients may benefit from increased pharmacological intervention to keep blood pressure controlled during the winter,” Robert Barrett, with the American Medical Association, Greenville, S.C., told this news organization.
“Individuals with hypertension or values near the range of hypertension may benefit from periodic blood pressure monitoring and improvements in physical activity and nutritional patterns during winter months to offset adverse effects from seasonal blood pressure changes,” Mr. Barrett added in a news release.
Mr. Barrett presented the study findings at the American Heart Association Hypertension Scientific Sessions 2023 in Boston.
Supportive data
Mr. Barrett explained that seasonal variation in BP has been previously documented, and as part of the evaluation for the AMA MAP Hypertension program, he and colleagues were interested in the effect of this variation on population control rates under standard metrics (visits with BP < 140/90 mm Hg).
They analyzed data from 60,676 men and women (mean age, 62 years) with hypertension from six health care organizations in the southeastern and midwestern United States that were participating in the quality improvement program.
During the roughly 5-year assessment period, none of the patients had changes in their antihypertensive medication, and all had at least one visit in each temperate season. The researchers estimated the seasonal effect on average systolic BP and BP control (defined as < 140/90 mm Hg).
Across a total of 453,787 visits, systolic BP during the winter averaged 0.47 mm Hg higher (95% confidence interval, 0.364-0.573) than the yearly average, with a significantly lower odds ratio for BP control (OR, 0.92; 95% CI, 0.91-0.94), the researchers report.
In contrast, average systolic BP was 0.92 mm Hg lower during the summer, with a higher likelihood of BP control (OR ,1.10; 95% CI, 1.07-1.12).
“Seasonal variation in blood pressure has a substantial effect on hypertension control, often defined as blood pressure < 140/90,” Barrett told this news organization.
“Patients with hypertension are less likely to have their blood pressure controlled during winter than summer months. If the blood pressure is very well controlled, for example to < 130/80, then seasonal variation will have little effect on control to < 140/90,” Mr. Barrett noted.
“However, if blood pressure is not well controlled, then patients near the 140/90 level could benefit from monitoring their blood pressure regularly, closer medical follow-up, and avoiding decreased physical activity and increased weight toward year end,” he added.
Wanpen Vongpatanasin, MD, clinical chair for the conference, said that it’s “well known that BP tends to lower during summer months and patients may be susceptible to dehydration and acute kidney injury when BP is too low, particularly when treated with certain medication such as diuretics.”
On the flip side, “cold weather predisposes to vasoconstriction as our blood vessel constrict to maintain core temperature and it could be challenging to manage BP. That’s why it is important for high BP patients to monitor home BP regularly,” said Dr. Vongpatanasin, professor of internal medicine and director of the hypertension section, cardiology division, UT Southwestern Medical Center, Dallas.
The study had no commercial funding. Mr. Barrett and Dr. Vongpatanasin have no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM HYPERTENSION 2023
‘New dawn’ for aldosterone as drug target in hypertension?
Once-daily treatment with the selective aldosterone synthase inhibitor lorundrostat (Mineralys Therapeutics) safely and significantly reduced blood pressure in adults with uncontrolled hypertension in a phase 2, randomized, controlled trial.
Eight weeks after adding lorundrostat (50 mg or 100 mg once daily) or placebo to background therapy, the medication lowered seated automated office systolic BP significantly more than placebo (−9.6 mm Hg with 50 mg; −7.8 mm Hg with 100 mg), with the greatest effects seen in adults with obesity.
“We need new drugs for treatment-resistant hypertension,” study investigator Steven Nissen, MD, chief academic officer at the Heart Vascular & Thoracic Institute at the Cleveland Clinic, said in an interview. Lorundrostat represents a “new class” of antihypertensive that “looks to be safe and we’re seeing very large reductions in blood pressure.”
Results of the Target-HTN trial were published online in JAMA to coincide with presentation at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
Aldosterone’s contribution ‘vastly underappreciated’
Excess aldosterone production contributes to uncontrolled BP in patients with obesity and other associated diseases, such as obstructive sleep apnea and metabolic syndrome.
“Aldosterone’s contribution to uncontrolled hypertension is vastly underappreciated,” first author and study presenter Luke Laffin, MD, also with the Cleveland Clinic, said in an interview.
Aldosterone synthase inhibitors are a novel class of BP-lowering medications that decrease aldosterone production. Lorundrostat is one of two such agents in advanced clinical development. The other is baxdrostat (CinCor Pharma/AstraZeneca).
The Target-HTN randomized, placebo-controlled, dose-ranging trial enrolled 200 adults (mean age, 66 years; 60% women) with uncontrolled hypertension while taking two or more antihypertensive medications; 42% of participants were taking three or more antihypertensive medications, 48% were obese and 40% had diabetes.
The study population was divided into two cohorts: an initial cohort of 163 adults with suppressed plasma renin activity at baseline (PRA ≤ 1.0 ng/mL per hour) and elevated plasma aldosterone (≥ 1.0 ng/dL) and a second cohort of 37 adults with PRA greater than 1.0 ng/mL per hour.
Participants were randomly assigned to placebo or one of five doses of lorundrostat in the initial cohort (12.5 mg, 50 mg, or 100 mg once daily or 12.5 mg or 25 mg twice daily).
In the second cohort, participants were randomly assigned (1:6) to placebo or lorundrostat 100 mg once daily. The primary endpoint was change in automated office systolic BP from baseline to week 8.
Among participants with suppressed PRA, following 8 weeks of treatment, changes in office systolic BP of −14.1, −13.2, and −6.9 mm Hg were observed with 100 mg, 50 mg, and 12.5 mg once-daily lorundrostat, respectively, compared with a change of −4.1 mm Hg with placebo.
Reductions in systolic BP in individuals receiving twice-daily doses of 25 mg and 12.5 mg of lorundrostat were −10.1 and −13.8 mm Hg, respectively.
Among participants without suppressed PRA, lorundrostat 100 mg once daily decreased systolic BP by 11.4 mm Hg, similar to BP reduction in those with suppressed PRA receiving the same dose.
A prespecified subgroup analysis showed that participants with obesity demonstrated greater BP lowering in response to lorundrostat.
No instances of cortisol insufficiency occurred. Six participants had increases in serum potassium above 6.0 mEq/L (6.0 mmol/L) that corrected with dose reduction or drug discontinuation.
The increase in serum potassium is “expected and manageable,” Dr. Laffin said in an interview. “Anytime you disrupt aldosterone production, you’re going to have to have an increase in serum potassium, but it’s very manageable and not something that is worrisome.”
A phase 2 trial in 300 adults with uncontrolled hypertension is currently underway. The trial will evaluate the BP-lowering effects of lorundrostat, administered on a background of a standardized antihypertensive medication regimen. A larger phase 3 study will start before the end of the year.
‘New dawn’ for therapies targeting aldosterone
The author of an editorial in JAMA noted that more 70 years after the first isolation of aldosterone, then called electrocortin, “there is a new dawn for therapies targeting aldosterone.”
“There is now real potential to provide better-targeted treatment for patients in whom aldosterone excess is known to contribute to their clinical condition and influence their clinical outcome, notably those with difficult-to-control hypertension, obesity, heart failure, chronic kidney disease, and the many with yet-to-be-diagnosed primary aldosteronism,” said Bryan Williams, MD, University College London.
The trial was funded by Mineralys Therapeutics, which is developing lorundrostat. Dr. Laffin reported that the Cleveland Clinic, his employer, was a study site for the Target-HTN trial and that C5Research, the academic research organization of the Cleveland Clinic, receives payment for services related to other Mineralys clinical trials. Dr. Laffin also reported receipt of personal fees from Medtronic, Lilly, and Crispr Therapeutics, grants from AstraZeneca, and stock options for LucidAct Health and Gordy Health. Dr. Nissen reported receipt of grants from Mineralys during the conduct of the study and grants from AbbVie, AstraZeneca, Amgen, Bristol-Myers Squibb, Lilly, Esperion Therapeutics, Medtronic, grants from MyoKardia, New Amsterdam Pharmaceuticals, Novartis, and Silence Therapeutics. Dr. Williams reported being the unremunerated chair of the steering committee designing a phase 3 trial of the aldosterone synthase inhibitor baxdrostat for AstraZeneca.
A version of this article first appeared on Medscape.com.
Once-daily treatment with the selective aldosterone synthase inhibitor lorundrostat (Mineralys Therapeutics) safely and significantly reduced blood pressure in adults with uncontrolled hypertension in a phase 2, randomized, controlled trial.
Eight weeks after adding lorundrostat (50 mg or 100 mg once daily) or placebo to background therapy, the medication lowered seated automated office systolic BP significantly more than placebo (−9.6 mm Hg with 50 mg; −7.8 mm Hg with 100 mg), with the greatest effects seen in adults with obesity.
“We need new drugs for treatment-resistant hypertension,” study investigator Steven Nissen, MD, chief academic officer at the Heart Vascular & Thoracic Institute at the Cleveland Clinic, said in an interview. Lorundrostat represents a “new class” of antihypertensive that “looks to be safe and we’re seeing very large reductions in blood pressure.”
Results of the Target-HTN trial were published online in JAMA to coincide with presentation at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
Aldosterone’s contribution ‘vastly underappreciated’
Excess aldosterone production contributes to uncontrolled BP in patients with obesity and other associated diseases, such as obstructive sleep apnea and metabolic syndrome.
“Aldosterone’s contribution to uncontrolled hypertension is vastly underappreciated,” first author and study presenter Luke Laffin, MD, also with the Cleveland Clinic, said in an interview.
Aldosterone synthase inhibitors are a novel class of BP-lowering medications that decrease aldosterone production. Lorundrostat is one of two such agents in advanced clinical development. The other is baxdrostat (CinCor Pharma/AstraZeneca).
The Target-HTN randomized, placebo-controlled, dose-ranging trial enrolled 200 adults (mean age, 66 years; 60% women) with uncontrolled hypertension while taking two or more antihypertensive medications; 42% of participants were taking three or more antihypertensive medications, 48% were obese and 40% had diabetes.
The study population was divided into two cohorts: an initial cohort of 163 adults with suppressed plasma renin activity at baseline (PRA ≤ 1.0 ng/mL per hour) and elevated plasma aldosterone (≥ 1.0 ng/dL) and a second cohort of 37 adults with PRA greater than 1.0 ng/mL per hour.
Participants were randomly assigned to placebo or one of five doses of lorundrostat in the initial cohort (12.5 mg, 50 mg, or 100 mg once daily or 12.5 mg or 25 mg twice daily).
In the second cohort, participants were randomly assigned (1:6) to placebo or lorundrostat 100 mg once daily. The primary endpoint was change in automated office systolic BP from baseline to week 8.
Among participants with suppressed PRA, following 8 weeks of treatment, changes in office systolic BP of −14.1, −13.2, and −6.9 mm Hg were observed with 100 mg, 50 mg, and 12.5 mg once-daily lorundrostat, respectively, compared with a change of −4.1 mm Hg with placebo.
Reductions in systolic BP in individuals receiving twice-daily doses of 25 mg and 12.5 mg of lorundrostat were −10.1 and −13.8 mm Hg, respectively.
Among participants without suppressed PRA, lorundrostat 100 mg once daily decreased systolic BP by 11.4 mm Hg, similar to BP reduction in those with suppressed PRA receiving the same dose.
A prespecified subgroup analysis showed that participants with obesity demonstrated greater BP lowering in response to lorundrostat.
No instances of cortisol insufficiency occurred. Six participants had increases in serum potassium above 6.0 mEq/L (6.0 mmol/L) that corrected with dose reduction or drug discontinuation.
The increase in serum potassium is “expected and manageable,” Dr. Laffin said in an interview. “Anytime you disrupt aldosterone production, you’re going to have to have an increase in serum potassium, but it’s very manageable and not something that is worrisome.”
A phase 2 trial in 300 adults with uncontrolled hypertension is currently underway. The trial will evaluate the BP-lowering effects of lorundrostat, administered on a background of a standardized antihypertensive medication regimen. A larger phase 3 study will start before the end of the year.
‘New dawn’ for therapies targeting aldosterone
The author of an editorial in JAMA noted that more 70 years after the first isolation of aldosterone, then called electrocortin, “there is a new dawn for therapies targeting aldosterone.”
“There is now real potential to provide better-targeted treatment for patients in whom aldosterone excess is known to contribute to their clinical condition and influence their clinical outcome, notably those with difficult-to-control hypertension, obesity, heart failure, chronic kidney disease, and the many with yet-to-be-diagnosed primary aldosteronism,” said Bryan Williams, MD, University College London.
The trial was funded by Mineralys Therapeutics, which is developing lorundrostat. Dr. Laffin reported that the Cleveland Clinic, his employer, was a study site for the Target-HTN trial and that C5Research, the academic research organization of the Cleveland Clinic, receives payment for services related to other Mineralys clinical trials. Dr. Laffin also reported receipt of personal fees from Medtronic, Lilly, and Crispr Therapeutics, grants from AstraZeneca, and stock options for LucidAct Health and Gordy Health. Dr. Nissen reported receipt of grants from Mineralys during the conduct of the study and grants from AbbVie, AstraZeneca, Amgen, Bristol-Myers Squibb, Lilly, Esperion Therapeutics, Medtronic, grants from MyoKardia, New Amsterdam Pharmaceuticals, Novartis, and Silence Therapeutics. Dr. Williams reported being the unremunerated chair of the steering committee designing a phase 3 trial of the aldosterone synthase inhibitor baxdrostat for AstraZeneca.
A version of this article first appeared on Medscape.com.
Once-daily treatment with the selective aldosterone synthase inhibitor lorundrostat (Mineralys Therapeutics) safely and significantly reduced blood pressure in adults with uncontrolled hypertension in a phase 2, randomized, controlled trial.
Eight weeks after adding lorundrostat (50 mg or 100 mg once daily) or placebo to background therapy, the medication lowered seated automated office systolic BP significantly more than placebo (−9.6 mm Hg with 50 mg; −7.8 mm Hg with 100 mg), with the greatest effects seen in adults with obesity.
“We need new drugs for treatment-resistant hypertension,” study investigator Steven Nissen, MD, chief academic officer at the Heart Vascular & Thoracic Institute at the Cleveland Clinic, said in an interview. Lorundrostat represents a “new class” of antihypertensive that “looks to be safe and we’re seeing very large reductions in blood pressure.”
Results of the Target-HTN trial were published online in JAMA to coincide with presentation at the Hypertension Scientific Sessions, sponsored by the American Heart Association.
Aldosterone’s contribution ‘vastly underappreciated’
Excess aldosterone production contributes to uncontrolled BP in patients with obesity and other associated diseases, such as obstructive sleep apnea and metabolic syndrome.
“Aldosterone’s contribution to uncontrolled hypertension is vastly underappreciated,” first author and study presenter Luke Laffin, MD, also with the Cleveland Clinic, said in an interview.
Aldosterone synthase inhibitors are a novel class of BP-lowering medications that decrease aldosterone production. Lorundrostat is one of two such agents in advanced clinical development. The other is baxdrostat (CinCor Pharma/AstraZeneca).
The Target-HTN randomized, placebo-controlled, dose-ranging trial enrolled 200 adults (mean age, 66 years; 60% women) with uncontrolled hypertension while taking two or more antihypertensive medications; 42% of participants were taking three or more antihypertensive medications, 48% were obese and 40% had diabetes.
The study population was divided into two cohorts: an initial cohort of 163 adults with suppressed plasma renin activity at baseline (PRA ≤ 1.0 ng/mL per hour) and elevated plasma aldosterone (≥ 1.0 ng/dL) and a second cohort of 37 adults with PRA greater than 1.0 ng/mL per hour.
Participants were randomly assigned to placebo or one of five doses of lorundrostat in the initial cohort (12.5 mg, 50 mg, or 100 mg once daily or 12.5 mg or 25 mg twice daily).
In the second cohort, participants were randomly assigned (1:6) to placebo or lorundrostat 100 mg once daily. The primary endpoint was change in automated office systolic BP from baseline to week 8.
Among participants with suppressed PRA, following 8 weeks of treatment, changes in office systolic BP of −14.1, −13.2, and −6.9 mm Hg were observed with 100 mg, 50 mg, and 12.5 mg once-daily lorundrostat, respectively, compared with a change of −4.1 mm Hg with placebo.
Reductions in systolic BP in individuals receiving twice-daily doses of 25 mg and 12.5 mg of lorundrostat were −10.1 and −13.8 mm Hg, respectively.
Among participants without suppressed PRA, lorundrostat 100 mg once daily decreased systolic BP by 11.4 mm Hg, similar to BP reduction in those with suppressed PRA receiving the same dose.
A prespecified subgroup analysis showed that participants with obesity demonstrated greater BP lowering in response to lorundrostat.
No instances of cortisol insufficiency occurred. Six participants had increases in serum potassium above 6.0 mEq/L (6.0 mmol/L) that corrected with dose reduction or drug discontinuation.
The increase in serum potassium is “expected and manageable,” Dr. Laffin said in an interview. “Anytime you disrupt aldosterone production, you’re going to have to have an increase in serum potassium, but it’s very manageable and not something that is worrisome.”
A phase 2 trial in 300 adults with uncontrolled hypertension is currently underway. The trial will evaluate the BP-lowering effects of lorundrostat, administered on a background of a standardized antihypertensive medication regimen. A larger phase 3 study will start before the end of the year.
‘New dawn’ for therapies targeting aldosterone
The author of an editorial in JAMA noted that more 70 years after the first isolation of aldosterone, then called electrocortin, “there is a new dawn for therapies targeting aldosterone.”
“There is now real potential to provide better-targeted treatment for patients in whom aldosterone excess is known to contribute to their clinical condition and influence their clinical outcome, notably those with difficult-to-control hypertension, obesity, heart failure, chronic kidney disease, and the many with yet-to-be-diagnosed primary aldosteronism,” said Bryan Williams, MD, University College London.
The trial was funded by Mineralys Therapeutics, which is developing lorundrostat. Dr. Laffin reported that the Cleveland Clinic, his employer, was a study site for the Target-HTN trial and that C5Research, the academic research organization of the Cleveland Clinic, receives payment for services related to other Mineralys clinical trials. Dr. Laffin also reported receipt of personal fees from Medtronic, Lilly, and Crispr Therapeutics, grants from AstraZeneca, and stock options for LucidAct Health and Gordy Health. Dr. Nissen reported receipt of grants from Mineralys during the conduct of the study and grants from AbbVie, AstraZeneca, Amgen, Bristol-Myers Squibb, Lilly, Esperion Therapeutics, Medtronic, grants from MyoKardia, New Amsterdam Pharmaceuticals, Novartis, and Silence Therapeutics. Dr. Williams reported being the unremunerated chair of the steering committee designing a phase 3 trial of the aldosterone synthase inhibitor baxdrostat for AstraZeneca.
A version of this article first appeared on Medscape.com.
FROM HYPERTENSION 2023
Exercise tied to lower mortality risk across cancer types
TOPLINE:
Regular exercise can significantly reduce a cancer survivor’s mortality from cancer or other causes, a large analysis finds.
METHODOLOGY:
- Following a cancer diagnosis, the impact of exercise on all cause and cause-specific mortality among survivors, and whether the benefit of exercise differs by cancer site, remains unclear.
- To investigate, researchers leveraged data from 11,480 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial.
- Postdiagnosis exercise levels were quantified via a questionnaire. The primary outcome was all-cause mortality; secondary endpoints were deaths from cancer and other causes.
- Cox models estimated cause-specific hazard ratio for all-cause mortality as well as cancer and noncancer mortality based on whether survivors met or did not meet exercise guidelines.
- Meeting national exercise guidelines meant moderate-intensity exercise 4 or more days per week with sessions lasting, on average, 30 minutes or longer; and/or strenuous-intensity exercise 2 or more days per week with sessions lasting, on average, 20 minutes or longer.
TAKEAWAY:
- Overall, 62% of participants were deemed nonexercisers (no exercise or exercise below guidelines) and 38% were classified as exercisers (meeting or exceeding guidelines). After a median follow-up of 16 years from diagnosis, researchers documented 4,665 deaths – 1,940 from cancer and 2,725 from other causes.
- Exercise at recommended levels was associated with “near-universal” all-cause mortality benefit for most cancers represented, including prostate, breast, endometrial, renal, and head and neck cancers.
- In multivariate analysis, compared with nonexercisers, exercisers had a 25% reduced risk of all-cause mortality (HR, 0.75), with the benefit apparent within 5 years and persisting for at least 20 years after diagnosis.
- Exercise was associated with a 21% reduction in cancer mortality and a 28% reduction in mortality from other causes, with more exercise demonstrating a greater benefit on cancer-specific mortality risk.
IN PRACTICE:
Overall, “our findings show exercise is a holistic strategy that may complement contemporary management approaches to further reduce cancer mortality (in select sites) while simultaneously lowering risk of death from other competing causes, which combine to improve all-cause mortality,” the authors conclude. “This benefit was observed within a few years after diagnosis and sustained for at least 20 years.”
SOURCE:
The study, led by Jessica Lavery, MS, Memorial Sloan Kettering Cancer Center, New York, was published online in the Journal of Clinical Oncology.
LIMITATIONS:
Exercise habits were self-reported at one time point, not measured more objectively over time using wearable devices. The population studied was predominantly non-Hispanic White. The researchers could not determine whether exercise habits reflected lower disease and/or treatment-related toxicities as opposed to direct exercise-induced effects or better adherence to a healthy lifestyle.
DISCLOSURES:
Support for the study was provided by AKTIV Against Cancer and grants from Memorial Sloan Kettering Cancer Center and UCLA Jonsson Comprehensive Cancer Center. Disclosures for the study authors are available with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
Regular exercise can significantly reduce a cancer survivor’s mortality from cancer or other causes, a large analysis finds.
METHODOLOGY:
- Following a cancer diagnosis, the impact of exercise on all cause and cause-specific mortality among survivors, and whether the benefit of exercise differs by cancer site, remains unclear.
- To investigate, researchers leveraged data from 11,480 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial.
- Postdiagnosis exercise levels were quantified via a questionnaire. The primary outcome was all-cause mortality; secondary endpoints were deaths from cancer and other causes.
- Cox models estimated cause-specific hazard ratio for all-cause mortality as well as cancer and noncancer mortality based on whether survivors met or did not meet exercise guidelines.
- Meeting national exercise guidelines meant moderate-intensity exercise 4 or more days per week with sessions lasting, on average, 30 minutes or longer; and/or strenuous-intensity exercise 2 or more days per week with sessions lasting, on average, 20 minutes or longer.
TAKEAWAY:
- Overall, 62% of participants were deemed nonexercisers (no exercise or exercise below guidelines) and 38% were classified as exercisers (meeting or exceeding guidelines). After a median follow-up of 16 years from diagnosis, researchers documented 4,665 deaths – 1,940 from cancer and 2,725 from other causes.
- Exercise at recommended levels was associated with “near-universal” all-cause mortality benefit for most cancers represented, including prostate, breast, endometrial, renal, and head and neck cancers.
- In multivariate analysis, compared with nonexercisers, exercisers had a 25% reduced risk of all-cause mortality (HR, 0.75), with the benefit apparent within 5 years and persisting for at least 20 years after diagnosis.
- Exercise was associated with a 21% reduction in cancer mortality and a 28% reduction in mortality from other causes, with more exercise demonstrating a greater benefit on cancer-specific mortality risk.
IN PRACTICE:
Overall, “our findings show exercise is a holistic strategy that may complement contemporary management approaches to further reduce cancer mortality (in select sites) while simultaneously lowering risk of death from other competing causes, which combine to improve all-cause mortality,” the authors conclude. “This benefit was observed within a few years after diagnosis and sustained for at least 20 years.”
SOURCE:
The study, led by Jessica Lavery, MS, Memorial Sloan Kettering Cancer Center, New York, was published online in the Journal of Clinical Oncology.
LIMITATIONS:
Exercise habits were self-reported at one time point, not measured more objectively over time using wearable devices. The population studied was predominantly non-Hispanic White. The researchers could not determine whether exercise habits reflected lower disease and/or treatment-related toxicities as opposed to direct exercise-induced effects or better adherence to a healthy lifestyle.
DISCLOSURES:
Support for the study was provided by AKTIV Against Cancer and grants from Memorial Sloan Kettering Cancer Center and UCLA Jonsson Comprehensive Cancer Center. Disclosures for the study authors are available with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
Regular exercise can significantly reduce a cancer survivor’s mortality from cancer or other causes, a large analysis finds.
METHODOLOGY:
- Following a cancer diagnosis, the impact of exercise on all cause and cause-specific mortality among survivors, and whether the benefit of exercise differs by cancer site, remains unclear.
- To investigate, researchers leveraged data from 11,480 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial.
- Postdiagnosis exercise levels were quantified via a questionnaire. The primary outcome was all-cause mortality; secondary endpoints were deaths from cancer and other causes.
- Cox models estimated cause-specific hazard ratio for all-cause mortality as well as cancer and noncancer mortality based on whether survivors met or did not meet exercise guidelines.
- Meeting national exercise guidelines meant moderate-intensity exercise 4 or more days per week with sessions lasting, on average, 30 minutes or longer; and/or strenuous-intensity exercise 2 or more days per week with sessions lasting, on average, 20 minutes or longer.
TAKEAWAY:
- Overall, 62% of participants were deemed nonexercisers (no exercise or exercise below guidelines) and 38% were classified as exercisers (meeting or exceeding guidelines). After a median follow-up of 16 years from diagnosis, researchers documented 4,665 deaths – 1,940 from cancer and 2,725 from other causes.
- Exercise at recommended levels was associated with “near-universal” all-cause mortality benefit for most cancers represented, including prostate, breast, endometrial, renal, and head and neck cancers.
- In multivariate analysis, compared with nonexercisers, exercisers had a 25% reduced risk of all-cause mortality (HR, 0.75), with the benefit apparent within 5 years and persisting for at least 20 years after diagnosis.
- Exercise was associated with a 21% reduction in cancer mortality and a 28% reduction in mortality from other causes, with more exercise demonstrating a greater benefit on cancer-specific mortality risk.
IN PRACTICE:
Overall, “our findings show exercise is a holistic strategy that may complement contemporary management approaches to further reduce cancer mortality (in select sites) while simultaneously lowering risk of death from other competing causes, which combine to improve all-cause mortality,” the authors conclude. “This benefit was observed within a few years after diagnosis and sustained for at least 20 years.”
SOURCE:
The study, led by Jessica Lavery, MS, Memorial Sloan Kettering Cancer Center, New York, was published online in the Journal of Clinical Oncology.
LIMITATIONS:
Exercise habits were self-reported at one time point, not measured more objectively over time using wearable devices. The population studied was predominantly non-Hispanic White. The researchers could not determine whether exercise habits reflected lower disease and/or treatment-related toxicities as opposed to direct exercise-induced effects or better adherence to a healthy lifestyle.
DISCLOSURES:
Support for the study was provided by AKTIV Against Cancer and grants from Memorial Sloan Kettering Cancer Center and UCLA Jonsson Comprehensive Cancer Center. Disclosures for the study authors are available with the original article.
A version of this article first appeared on Medscape.com.
Positive topline results for antihypertensive zilebesiran
Zilebesiran (Alnylam Pharmaceuticals), an investigational, subcutaneously administered small-interfering RNA (siRNA) therapeutic in development for the treatment of hypertension, met the primary and secondary endpoints, with an “encouraging” safety profile in the phase 2 KARDIA-1 study, the company announced.
KARDIA-1 is a phase 2 randomized, double-blind, placebo-controlled, dose-ranging study evaluating the efficacy and safety of zilebesiran as monotherapy in 394 adults with mild to moderate untreated hypertension or on stable therapy with one or more antihypertensive drugs.
Patients were randomly assigned to one of five treatment arms during a 12-month double-blind period and double-blind extension period: 150 mg or 300 mg zilebesiran subcutaneously once every 6 months, 300 mg or 600 mg zilebesiran subcutaneously once every 3 months, or placebo. Patients taking placebo were randomly assigned to one of the four initial zilebesiran dose regimens beginning at month 6.
The primary endpoint was change from baseline in systolic blood pressure (SBP) at 3 months assessed by 24-hour ambulatory blood pressure monitoring.
Topline data show a dose-dependent, clinically significant reduction in 24-hour mean SBP, with a placebo-subtracted reduction greater than 15 mm Hg (P < .0001) with both the 300 mg and 600 mg doses.
The study also met key secondary endpoints, showing “consistent and sustained reductions” in SBP at 6 months, which supports quarterly or biannual dosing, the company said.
There was one death due to cardiopulmonary arrest in a zilebesiran-treated patient that was considered unrelated to the drug. Serious adverse events were reported in 3.6% of zilebesiran-treated patients and 6.7% of placebo-treated patients. None was considered related to the study drug.
Adverse events occurring in 5% or more of zilebesiran-treated patients in any dose arm included COVID-19, injection-site reaction, hyperkalemia, hypertension, upper respiratory tract infection, arthralgia, and headache.
“As a physician, I believe these KARDIA-1 results, which demonstrate clinically significant reductions in systolic blood pressure of greater than 15 mm Hg, along with the ability to achieve durable tonic blood pressure control, provide hope that we may one day have access to a novel therapy with the potential to address the significant unmet needs of patients with uncontrolled hypertension who are at high risk of future cardiovascular events,” study investigator George L. Bakris, MD, director, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, said in a statement.
The phase 2 results “further validate” the phase 1 results, published in the New England Journal of Medicine, Simon Fox, PhD, vice president, zilebesiran program lead at Alnylam, said in the statement.
The full KARDIA-1 results will be reported at an upcoming scientific conference, the statement notes. Topline results from the KARDIA-2 phase 2 study of zilebesiran in combination with one of three standard classes of antihypertensive medications in patients with mild to moderate hypertension are expected in early 2024.
A version of this article first appeared on Medscape.com.
Zilebesiran (Alnylam Pharmaceuticals), an investigational, subcutaneously administered small-interfering RNA (siRNA) therapeutic in development for the treatment of hypertension, met the primary and secondary endpoints, with an “encouraging” safety profile in the phase 2 KARDIA-1 study, the company announced.
KARDIA-1 is a phase 2 randomized, double-blind, placebo-controlled, dose-ranging study evaluating the efficacy and safety of zilebesiran as monotherapy in 394 adults with mild to moderate untreated hypertension or on stable therapy with one or more antihypertensive drugs.
Patients were randomly assigned to one of five treatment arms during a 12-month double-blind period and double-blind extension period: 150 mg or 300 mg zilebesiran subcutaneously once every 6 months, 300 mg or 600 mg zilebesiran subcutaneously once every 3 months, or placebo. Patients taking placebo were randomly assigned to one of the four initial zilebesiran dose regimens beginning at month 6.
The primary endpoint was change from baseline in systolic blood pressure (SBP) at 3 months assessed by 24-hour ambulatory blood pressure monitoring.
Topline data show a dose-dependent, clinically significant reduction in 24-hour mean SBP, with a placebo-subtracted reduction greater than 15 mm Hg (P < .0001) with both the 300 mg and 600 mg doses.
The study also met key secondary endpoints, showing “consistent and sustained reductions” in SBP at 6 months, which supports quarterly or biannual dosing, the company said.
There was one death due to cardiopulmonary arrest in a zilebesiran-treated patient that was considered unrelated to the drug. Serious adverse events were reported in 3.6% of zilebesiran-treated patients and 6.7% of placebo-treated patients. None was considered related to the study drug.
Adverse events occurring in 5% or more of zilebesiran-treated patients in any dose arm included COVID-19, injection-site reaction, hyperkalemia, hypertension, upper respiratory tract infection, arthralgia, and headache.
“As a physician, I believe these KARDIA-1 results, which demonstrate clinically significant reductions in systolic blood pressure of greater than 15 mm Hg, along with the ability to achieve durable tonic blood pressure control, provide hope that we may one day have access to a novel therapy with the potential to address the significant unmet needs of patients with uncontrolled hypertension who are at high risk of future cardiovascular events,” study investigator George L. Bakris, MD, director, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, said in a statement.
The phase 2 results “further validate” the phase 1 results, published in the New England Journal of Medicine, Simon Fox, PhD, vice president, zilebesiran program lead at Alnylam, said in the statement.
The full KARDIA-1 results will be reported at an upcoming scientific conference, the statement notes. Topline results from the KARDIA-2 phase 2 study of zilebesiran in combination with one of three standard classes of antihypertensive medications in patients with mild to moderate hypertension are expected in early 2024.
A version of this article first appeared on Medscape.com.
Zilebesiran (Alnylam Pharmaceuticals), an investigational, subcutaneously administered small-interfering RNA (siRNA) therapeutic in development for the treatment of hypertension, met the primary and secondary endpoints, with an “encouraging” safety profile in the phase 2 KARDIA-1 study, the company announced.
KARDIA-1 is a phase 2 randomized, double-blind, placebo-controlled, dose-ranging study evaluating the efficacy and safety of zilebesiran as monotherapy in 394 adults with mild to moderate untreated hypertension or on stable therapy with one or more antihypertensive drugs.
Patients were randomly assigned to one of five treatment arms during a 12-month double-blind period and double-blind extension period: 150 mg or 300 mg zilebesiran subcutaneously once every 6 months, 300 mg or 600 mg zilebesiran subcutaneously once every 3 months, or placebo. Patients taking placebo were randomly assigned to one of the four initial zilebesiran dose regimens beginning at month 6.
The primary endpoint was change from baseline in systolic blood pressure (SBP) at 3 months assessed by 24-hour ambulatory blood pressure monitoring.
Topline data show a dose-dependent, clinically significant reduction in 24-hour mean SBP, with a placebo-subtracted reduction greater than 15 mm Hg (P < .0001) with both the 300 mg and 600 mg doses.
The study also met key secondary endpoints, showing “consistent and sustained reductions” in SBP at 6 months, which supports quarterly or biannual dosing, the company said.
There was one death due to cardiopulmonary arrest in a zilebesiran-treated patient that was considered unrelated to the drug. Serious adverse events were reported in 3.6% of zilebesiran-treated patients and 6.7% of placebo-treated patients. None was considered related to the study drug.
Adverse events occurring in 5% or more of zilebesiran-treated patients in any dose arm included COVID-19, injection-site reaction, hyperkalemia, hypertension, upper respiratory tract infection, arthralgia, and headache.
“As a physician, I believe these KARDIA-1 results, which demonstrate clinically significant reductions in systolic blood pressure of greater than 15 mm Hg, along with the ability to achieve durable tonic blood pressure control, provide hope that we may one day have access to a novel therapy with the potential to address the significant unmet needs of patients with uncontrolled hypertension who are at high risk of future cardiovascular events,” study investigator George L. Bakris, MD, director, American Heart Association Comprehensive Hypertension Center, University of Chicago Medicine, said in a statement.
The phase 2 results “further validate” the phase 1 results, published in the New England Journal of Medicine, Simon Fox, PhD, vice president, zilebesiran program lead at Alnylam, said in the statement.
The full KARDIA-1 results will be reported at an upcoming scientific conference, the statement notes. Topline results from the KARDIA-2 phase 2 study of zilebesiran in combination with one of three standard classes of antihypertensive medications in patients with mild to moderate hypertension are expected in early 2024.
A version of this article first appeared on Medscape.com.
NAFLD raises risk for colorectal adenomatous polyps
TOPLINE:
Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for precancerous colorectal adenomatous polyps in men and women, according to results of a large study.
METHODOLOGY:
- Researchers conducted a retrospective review of the medical records of adults who underwent abdominal ultrasound and colonoscopy at a single hospital in China from January 2018 to December 2022 to determine NAFLD status and presence of polyps.
- Multivariate logistic regression analysis was used to detect associations between NAFLD and adenomatous and nonadenomatous polyps.
TAKEAWAY:
- Overall, 36.6% of the 3,028 patients had adenomatous polyps, 10.7% had nonadenomatous polyps, and 52.7% were polyp free.
- The higher frequency of NAFLD was significant in adults with adenomatous polyps (66.9%) but not in patients with nonadenomatous polyps (57%) vs. adults with no polyps (52.3%).
- In the fully adjusted model, NAFLD was a significant independent risk factor for adenomatous polyps (odds ratio [OR], 1.6; P < .0001) but not for nonadenomatous polyps (OR, 1.0; P = .813).
- The association between NAFLD and adenomatous polyps was statistically significant in both men (OR, 1.8) and women (OR, 1.4).
IN PRACTICE:
“Our results clearly demonstrated that NAFLD is associated with the development of colorectal adenomatous polyps in males and females, but is not associated with an increased risk of nonadenomatous polyps. The findings provide new insight into the prevention of colorectal cancer in NAFLD patients,” the authors wrote.
SOURCE:
The study was co-led by Yingxue Yang and Yajie Teng, The First People’s Hospital of Kunshan, Suzhou, China. It was published online in the European Journal of Gastroenterology & Hepatology. The study had no specific funding.
LIMITATIONS:
The diagnosis of NAFLD was by ultrasound rather than by liver biopsy. The study’s cross-sectional design precludes conclusions about causality between NAFLD and the risk for colorectal adenomatous polyps. The study involved a single center.
DISCLOSURES:
The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for precancerous colorectal adenomatous polyps in men and women, according to results of a large study.
METHODOLOGY:
- Researchers conducted a retrospective review of the medical records of adults who underwent abdominal ultrasound and colonoscopy at a single hospital in China from January 2018 to December 2022 to determine NAFLD status and presence of polyps.
- Multivariate logistic regression analysis was used to detect associations between NAFLD and adenomatous and nonadenomatous polyps.
TAKEAWAY:
- Overall, 36.6% of the 3,028 patients had adenomatous polyps, 10.7% had nonadenomatous polyps, and 52.7% were polyp free.
- The higher frequency of NAFLD was significant in adults with adenomatous polyps (66.9%) but not in patients with nonadenomatous polyps (57%) vs. adults with no polyps (52.3%).
- In the fully adjusted model, NAFLD was a significant independent risk factor for adenomatous polyps (odds ratio [OR], 1.6; P < .0001) but not for nonadenomatous polyps (OR, 1.0; P = .813).
- The association between NAFLD and adenomatous polyps was statistically significant in both men (OR, 1.8) and women (OR, 1.4).
IN PRACTICE:
“Our results clearly demonstrated that NAFLD is associated with the development of colorectal adenomatous polyps in males and females, but is not associated with an increased risk of nonadenomatous polyps. The findings provide new insight into the prevention of colorectal cancer in NAFLD patients,” the authors wrote.
SOURCE:
The study was co-led by Yingxue Yang and Yajie Teng, The First People’s Hospital of Kunshan, Suzhou, China. It was published online in the European Journal of Gastroenterology & Hepatology. The study had no specific funding.
LIMITATIONS:
The diagnosis of NAFLD was by ultrasound rather than by liver biopsy. The study’s cross-sectional design precludes conclusions about causality between NAFLD and the risk for colorectal adenomatous polyps. The study involved a single center.
DISCLOSURES:
The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for precancerous colorectal adenomatous polyps in men and women, according to results of a large study.
METHODOLOGY:
- Researchers conducted a retrospective review of the medical records of adults who underwent abdominal ultrasound and colonoscopy at a single hospital in China from January 2018 to December 2022 to determine NAFLD status and presence of polyps.
- Multivariate logistic regression analysis was used to detect associations between NAFLD and adenomatous and nonadenomatous polyps.
TAKEAWAY:
- Overall, 36.6% of the 3,028 patients had adenomatous polyps, 10.7% had nonadenomatous polyps, and 52.7% were polyp free.
- The higher frequency of NAFLD was significant in adults with adenomatous polyps (66.9%) but not in patients with nonadenomatous polyps (57%) vs. adults with no polyps (52.3%).
- In the fully adjusted model, NAFLD was a significant independent risk factor for adenomatous polyps (odds ratio [OR], 1.6; P < .0001) but not for nonadenomatous polyps (OR, 1.0; P = .813).
- The association between NAFLD and adenomatous polyps was statistically significant in both men (OR, 1.8) and women (OR, 1.4).
IN PRACTICE:
“Our results clearly demonstrated that NAFLD is associated with the development of colorectal adenomatous polyps in males and females, but is not associated with an increased risk of nonadenomatous polyps. The findings provide new insight into the prevention of colorectal cancer in NAFLD patients,” the authors wrote.
SOURCE:
The study was co-led by Yingxue Yang and Yajie Teng, The First People’s Hospital of Kunshan, Suzhou, China. It was published online in the European Journal of Gastroenterology & Hepatology. The study had no specific funding.
LIMITATIONS:
The diagnosis of NAFLD was by ultrasound rather than by liver biopsy. The study’s cross-sectional design precludes conclusions about causality between NAFLD and the risk for colorectal adenomatous polyps. The study involved a single center.
DISCLOSURES:
The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
New European restrictions on topiramate in pregnancy
While it’s well known that topiramate can cause major congenital malformations and fetal growth restriction when used during pregnancy, recent data also suggest a possibly increased risk for neurodevelopmental disorders when topiramate is used during pregnancy, the EMA said in a statement.
The data include two observational studies that showed children born to mothers with epilepsy and who were exposed to topiramate in the womb may have a two- to threefold higher risk for neurodevelopmental disorders, in particular autism spectrum disorders (ASD), intellectual disability, or attention deficit hyperactivity disorder (ADHD), compared with children born to mothers with epilepsy not taking antiepileptic medication.
For patients using topiramate for the treatment of epilepsy, the PRAC now recommends that the medicine not be used during pregnancy unless no other suitable treatment is available.
The PRAC had also recommended a pregnancy prevention program to avoid exposure of the developing fetus to topiramate. “These measures will inform any woman or girl who is able to have children of the risks of taking topiramate during pregnancy and the need to avoid becoming pregnant while taking topiramate,” the EMA said.
Regardless of indication, the agency said topiramate should be used in women of childbearing age only when the following conditions of the pregnancy prevention program are met:
- A pregnancy test before starting treatment.
- Counseling about the risks of topiramate treatment and the need for highly effective contraception throughout treatment.
- A review of ongoing treatment at least annually by completion of a risk awareness form.
The PRAC recommends that health care professionals ensure women of childbearing age are fully aware of the risks of taking topiramate during pregnancy. The committee noted that alternative treatment options should be considered and the need for topiramate treatment should be reassessed at least annually.
The product information for topiramate-containing medicines will be updated to further highlight the risks for neurodevelopmental disorders and the additional safety measures to be taken.
Patients and health care professionals will be provided with educational materials regarding the risks of using topiramate during pregnancy, and a patient card will be provided to the patient with each medicine package. A visible warning will also be added to the outer packaging of the medicine.
The new PRAC recommendations will be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position.
A version of this article first appeared on Medscape.com.
While it’s well known that topiramate can cause major congenital malformations and fetal growth restriction when used during pregnancy, recent data also suggest a possibly increased risk for neurodevelopmental disorders when topiramate is used during pregnancy, the EMA said in a statement.
The data include two observational studies that showed children born to mothers with epilepsy and who were exposed to topiramate in the womb may have a two- to threefold higher risk for neurodevelopmental disorders, in particular autism spectrum disorders (ASD), intellectual disability, or attention deficit hyperactivity disorder (ADHD), compared with children born to mothers with epilepsy not taking antiepileptic medication.
For patients using topiramate for the treatment of epilepsy, the PRAC now recommends that the medicine not be used during pregnancy unless no other suitable treatment is available.
The PRAC had also recommended a pregnancy prevention program to avoid exposure of the developing fetus to topiramate. “These measures will inform any woman or girl who is able to have children of the risks of taking topiramate during pregnancy and the need to avoid becoming pregnant while taking topiramate,” the EMA said.
Regardless of indication, the agency said topiramate should be used in women of childbearing age only when the following conditions of the pregnancy prevention program are met:
- A pregnancy test before starting treatment.
- Counseling about the risks of topiramate treatment and the need for highly effective contraception throughout treatment.
- A review of ongoing treatment at least annually by completion of a risk awareness form.
The PRAC recommends that health care professionals ensure women of childbearing age are fully aware of the risks of taking topiramate during pregnancy. The committee noted that alternative treatment options should be considered and the need for topiramate treatment should be reassessed at least annually.
The product information for topiramate-containing medicines will be updated to further highlight the risks for neurodevelopmental disorders and the additional safety measures to be taken.
Patients and health care professionals will be provided with educational materials regarding the risks of using topiramate during pregnancy, and a patient card will be provided to the patient with each medicine package. A visible warning will also be added to the outer packaging of the medicine.
The new PRAC recommendations will be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position.
A version of this article first appeared on Medscape.com.
While it’s well known that topiramate can cause major congenital malformations and fetal growth restriction when used during pregnancy, recent data also suggest a possibly increased risk for neurodevelopmental disorders when topiramate is used during pregnancy, the EMA said in a statement.
The data include two observational studies that showed children born to mothers with epilepsy and who were exposed to topiramate in the womb may have a two- to threefold higher risk for neurodevelopmental disorders, in particular autism spectrum disorders (ASD), intellectual disability, or attention deficit hyperactivity disorder (ADHD), compared with children born to mothers with epilepsy not taking antiepileptic medication.
For patients using topiramate for the treatment of epilepsy, the PRAC now recommends that the medicine not be used during pregnancy unless no other suitable treatment is available.
The PRAC had also recommended a pregnancy prevention program to avoid exposure of the developing fetus to topiramate. “These measures will inform any woman or girl who is able to have children of the risks of taking topiramate during pregnancy and the need to avoid becoming pregnant while taking topiramate,” the EMA said.
Regardless of indication, the agency said topiramate should be used in women of childbearing age only when the following conditions of the pregnancy prevention program are met:
- A pregnancy test before starting treatment.
- Counseling about the risks of topiramate treatment and the need for highly effective contraception throughout treatment.
- A review of ongoing treatment at least annually by completion of a risk awareness form.
The PRAC recommends that health care professionals ensure women of childbearing age are fully aware of the risks of taking topiramate during pregnancy. The committee noted that alternative treatment options should be considered and the need for topiramate treatment should be reassessed at least annually.
The product information for topiramate-containing medicines will be updated to further highlight the risks for neurodevelopmental disorders and the additional safety measures to be taken.
Patients and health care professionals will be provided with educational materials regarding the risks of using topiramate during pregnancy, and a patient card will be provided to the patient with each medicine package. A visible warning will also be added to the outer packaging of the medicine.
The new PRAC recommendations will be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt a position.
A version of this article first appeared on Medscape.com.
Hidden disparities: How language barriers reduce cancer care access
TOPLINE:
, a new study suggests.
METHODOLOGY:
- Language barriers between patients and physicians negatively affect the quality of care patients receive; however, less is known about how language barriers may affect patients’ access to cancer care.
- Researchers examined the impact of patients’ spoken language on their access to care for three types of cancer that disproportionately affect Hispanic and Asian populations (colon, lung, and thyroid cancer).
- Trained investigators who speak English, Spanish, or Mandarin called the general information line of 144 US hospitals in 12 states seeking an appointment.
- The primary outcome was whether the simulated patient caller was provided with next steps to access cancer care, defined as being given a clinic number or clinic transfer.
TAKEAWAY:
- Of the 1,296 calls made (432 in each language), 53% resulted in the caller receiving next steps to access cancer care.
- Spanish- and Mandarin-speaking callers were significantly less likely to receive information on next steps (37.7% and 27.5%, respectively), compared with English-speaking callers (93.5%).
- In multivariable logistic regression, non–English-speaking callers had lower odds of being given next steps to access cancer care (odds ratio, 0.04 for Spanish speakers; OR, 0.02 for Mandarin speakers).
- Compared with calls to teaching hospitals, calls to nonteaching hospitals were associated with lower odds of simulated callers receiving this next-step information (OR, 0.43).
IN PRACTICE:
“Our study provides actionable insights into existing linguistic disparities in cancer care access due to systems-level barriers present prior to evaluation by a physician,” the authors concluded. It is essential to “engage in efforts to mitigate these communication barriers that disproportionately impact the health of vulnerable patient populations with cancer.”
SOURCE:
The study, led by Debbie Chen, MD, University of Michigan, Ann Arbor, was published online Sept. 5 in the Journal of the National Comprehensive Cancer Network.
LIMITATIONS:
The researchers only assessed responses from the hospital general information line, and the findings do not reflect the type or quality of cancer care a patient may have received once seen and treated. The study did not capture the complexities of hospital call center workflows, which limited the authors’ ability to discern the reasons behind the observed outcomes.
DISCLOSURES:
The study was supported by the University of Michigan’s Rogel Cancer Center and the National Institute of Diabetes and Digestive and Kidney Diseases . The authors have disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
, a new study suggests.
METHODOLOGY:
- Language barriers between patients and physicians negatively affect the quality of care patients receive; however, less is known about how language barriers may affect patients’ access to cancer care.
- Researchers examined the impact of patients’ spoken language on their access to care for three types of cancer that disproportionately affect Hispanic and Asian populations (colon, lung, and thyroid cancer).
- Trained investigators who speak English, Spanish, or Mandarin called the general information line of 144 US hospitals in 12 states seeking an appointment.
- The primary outcome was whether the simulated patient caller was provided with next steps to access cancer care, defined as being given a clinic number or clinic transfer.
TAKEAWAY:
- Of the 1,296 calls made (432 in each language), 53% resulted in the caller receiving next steps to access cancer care.
- Spanish- and Mandarin-speaking callers were significantly less likely to receive information on next steps (37.7% and 27.5%, respectively), compared with English-speaking callers (93.5%).
- In multivariable logistic regression, non–English-speaking callers had lower odds of being given next steps to access cancer care (odds ratio, 0.04 for Spanish speakers; OR, 0.02 for Mandarin speakers).
- Compared with calls to teaching hospitals, calls to nonteaching hospitals were associated with lower odds of simulated callers receiving this next-step information (OR, 0.43).
IN PRACTICE:
“Our study provides actionable insights into existing linguistic disparities in cancer care access due to systems-level barriers present prior to evaluation by a physician,” the authors concluded. It is essential to “engage in efforts to mitigate these communication barriers that disproportionately impact the health of vulnerable patient populations with cancer.”
SOURCE:
The study, led by Debbie Chen, MD, University of Michigan, Ann Arbor, was published online Sept. 5 in the Journal of the National Comprehensive Cancer Network.
LIMITATIONS:
The researchers only assessed responses from the hospital general information line, and the findings do not reflect the type or quality of cancer care a patient may have received once seen and treated. The study did not capture the complexities of hospital call center workflows, which limited the authors’ ability to discern the reasons behind the observed outcomes.
DISCLOSURES:
The study was supported by the University of Michigan’s Rogel Cancer Center and the National Institute of Diabetes and Digestive and Kidney Diseases . The authors have disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
, a new study suggests.
METHODOLOGY:
- Language barriers between patients and physicians negatively affect the quality of care patients receive; however, less is known about how language barriers may affect patients’ access to cancer care.
- Researchers examined the impact of patients’ spoken language on their access to care for three types of cancer that disproportionately affect Hispanic and Asian populations (colon, lung, and thyroid cancer).
- Trained investigators who speak English, Spanish, or Mandarin called the general information line of 144 US hospitals in 12 states seeking an appointment.
- The primary outcome was whether the simulated patient caller was provided with next steps to access cancer care, defined as being given a clinic number or clinic transfer.
TAKEAWAY:
- Of the 1,296 calls made (432 in each language), 53% resulted in the caller receiving next steps to access cancer care.
- Spanish- and Mandarin-speaking callers were significantly less likely to receive information on next steps (37.7% and 27.5%, respectively), compared with English-speaking callers (93.5%).
- In multivariable logistic regression, non–English-speaking callers had lower odds of being given next steps to access cancer care (odds ratio, 0.04 for Spanish speakers; OR, 0.02 for Mandarin speakers).
- Compared with calls to teaching hospitals, calls to nonteaching hospitals were associated with lower odds of simulated callers receiving this next-step information (OR, 0.43).
IN PRACTICE:
“Our study provides actionable insights into existing linguistic disparities in cancer care access due to systems-level barriers present prior to evaluation by a physician,” the authors concluded. It is essential to “engage in efforts to mitigate these communication barriers that disproportionately impact the health of vulnerable patient populations with cancer.”
SOURCE:
The study, led by Debbie Chen, MD, University of Michigan, Ann Arbor, was published online Sept. 5 in the Journal of the National Comprehensive Cancer Network.
LIMITATIONS:
The researchers only assessed responses from the hospital general information line, and the findings do not reflect the type or quality of cancer care a patient may have received once seen and treated. The study did not capture the complexities of hospital call center workflows, which limited the authors’ ability to discern the reasons behind the observed outcomes.
DISCLOSURES:
The study was supported by the University of Michigan’s Rogel Cancer Center and the National Institute of Diabetes and Digestive and Kidney Diseases . The authors have disclosed no relevant conflicts of interest.
A version of this article appeared on Medscape.com.
FROM JNCCN