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Monitoring Tech for Pulmonary Disorders Moving Beyond Wearables
, but, as with any emergent technology, pitfalls come along with the promise and potential.
Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.
“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.
“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”
Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).
Targeting Challenges With Polysomnography
All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.
“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.
“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”
Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.
“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”
However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.
The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.
And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.
The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.
“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.
These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”
Early Study of Ingestible Capsule
To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.
The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.
Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.
In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.
Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.
The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”
The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.
“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.
This platform could also collect multinight data for sleep studies, he added.
“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”
AI-Aided Stethoscope
The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.
The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.
The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.
“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”
Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.
, but, as with any emergent technology, pitfalls come along with the promise and potential.
Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.
“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.
“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”
Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).
Targeting Challenges With Polysomnography
All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.
“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.
“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”
Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.
“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”
However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.
The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.
And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.
The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.
“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.
These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”
Early Study of Ingestible Capsule
To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.
The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.
Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.
In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.
Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.
The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”
The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.
“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.
This platform could also collect multinight data for sleep studies, he added.
“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”
AI-Aided Stethoscope
The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.
The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.
The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.
“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”
Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.
, but, as with any emergent technology, pitfalls come along with the promise and potential.
Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.
“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.
“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”
Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).
Targeting Challenges With Polysomnography
All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.
“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.
“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”
Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.
“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”
However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.
The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.
And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.
The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.
“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.
These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”
Early Study of Ingestible Capsule
To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.
The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.
Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.
In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.
Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.
The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”
The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.
“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.
This platform could also collect multinight data for sleep studies, he added.
“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”
AI-Aided Stethoscope
The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.
The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.
The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.
“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”
Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.
FDA approves implant for glaucoma
The iDose TR (Glaukos Corp) is inserted into a corneal incision on the temple side of the eye. Pivotal phase 3 clinical trials showed the treatment resulted in sustained reductions in IOP for 3 months ranging from 6.6 to 8.4 mm Hg, comparable to reductions with topical timolol 0.5% drops used twice daily. Normal IOP is 10-21 mm Hg, and glaucoma treatments are designed to reduce high IOP into the normal range.
Glaukos Corp said that it intends a commercial launch of the implant early in 2024, with a wholesale cost of $13,950 per implant.
Travoprost is a prostaglandin analog that has been long used as a topical formulation for lowering IOP in OAG and OHT. Timolol is a topical beta-blocker widely used for the same indications.
iDose TR comes in a preloaded handheld injector designed to deliver the implant into the sclera of the eye. The implant seats in the junction of the iris, sclera, and cornea.
In two phase 3 clinical trials, 81% of patients who received the iDose TR did not require supplemental drops to reduce IOP after 12 months compared with 95% of those who receive timolol alone.
The phase 3 trials included 1150 participants across 89 clinical sites. Both trials, GC-010 and GC-012, met the primary endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months, according to results that John Berdahl, MD, a researcher with Vance Thompson Vision in Sioux Falls, South Dakota, and an investigator for Glaukos, presented in May at the annual meeting of the American Society of Cataract and Refractive Surgery.
Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated noninferiority to topical timolol in reduction of IOP during the first 3 months of treatment. The agency also noted that use of iDose TR did not demonstrate noninferiority over the next 9 months.
In the controlled studies, the most common ocular adverse reactions reported in 2% to 6% of patients who received iDose TR were increases in IOP , iritis, dry eye, and defects of the visual field, most of which were said to be mild and transient in nature.
A version of this article appeared on Medscape.com.
The iDose TR (Glaukos Corp) is inserted into a corneal incision on the temple side of the eye. Pivotal phase 3 clinical trials showed the treatment resulted in sustained reductions in IOP for 3 months ranging from 6.6 to 8.4 mm Hg, comparable to reductions with topical timolol 0.5% drops used twice daily. Normal IOP is 10-21 mm Hg, and glaucoma treatments are designed to reduce high IOP into the normal range.
Glaukos Corp said that it intends a commercial launch of the implant early in 2024, with a wholesale cost of $13,950 per implant.
Travoprost is a prostaglandin analog that has been long used as a topical formulation for lowering IOP in OAG and OHT. Timolol is a topical beta-blocker widely used for the same indications.
iDose TR comes in a preloaded handheld injector designed to deliver the implant into the sclera of the eye. The implant seats in the junction of the iris, sclera, and cornea.
In two phase 3 clinical trials, 81% of patients who received the iDose TR did not require supplemental drops to reduce IOP after 12 months compared with 95% of those who receive timolol alone.
The phase 3 trials included 1150 participants across 89 clinical sites. Both trials, GC-010 and GC-012, met the primary endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months, according to results that John Berdahl, MD, a researcher with Vance Thompson Vision in Sioux Falls, South Dakota, and an investigator for Glaukos, presented in May at the annual meeting of the American Society of Cataract and Refractive Surgery.
Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated noninferiority to topical timolol in reduction of IOP during the first 3 months of treatment. The agency also noted that use of iDose TR did not demonstrate noninferiority over the next 9 months.
In the controlled studies, the most common ocular adverse reactions reported in 2% to 6% of patients who received iDose TR were increases in IOP , iritis, dry eye, and defects of the visual field, most of which were said to be mild and transient in nature.
A version of this article appeared on Medscape.com.
The iDose TR (Glaukos Corp) is inserted into a corneal incision on the temple side of the eye. Pivotal phase 3 clinical trials showed the treatment resulted in sustained reductions in IOP for 3 months ranging from 6.6 to 8.4 mm Hg, comparable to reductions with topical timolol 0.5% drops used twice daily. Normal IOP is 10-21 mm Hg, and glaucoma treatments are designed to reduce high IOP into the normal range.
Glaukos Corp said that it intends a commercial launch of the implant early in 2024, with a wholesale cost of $13,950 per implant.
Travoprost is a prostaglandin analog that has been long used as a topical formulation for lowering IOP in OAG and OHT. Timolol is a topical beta-blocker widely used for the same indications.
iDose TR comes in a preloaded handheld injector designed to deliver the implant into the sclera of the eye. The implant seats in the junction of the iris, sclera, and cornea.
In two phase 3 clinical trials, 81% of patients who received the iDose TR did not require supplemental drops to reduce IOP after 12 months compared with 95% of those who receive timolol alone.
The phase 3 trials included 1150 participants across 89 clinical sites. Both trials, GC-010 and GC-012, met the primary endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months, according to results that John Berdahl, MD, a researcher with Vance Thompson Vision in Sioux Falls, South Dakota, and an investigator for Glaukos, presented in May at the annual meeting of the American Society of Cataract and Refractive Surgery.
Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated noninferiority to topical timolol in reduction of IOP during the first 3 months of treatment. The agency also noted that use of iDose TR did not demonstrate noninferiority over the next 9 months.
In the controlled studies, the most common ocular adverse reactions reported in 2% to 6% of patients who received iDose TR were increases in IOP , iritis, dry eye, and defects of the visual field, most of which were said to be mild and transient in nature.
A version of this article appeared on Medscape.com.
Report: CKD Severity Linked to Thinning of Retina, Choroid Layers
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
FROM NATURE COMMUNICATIONS
New PCSK9 inhibitor allows 3-month treatment intervals
PHILADELPHIA – An investigational PCSK9 inhibitor that can be injected every 1-3 months as add-on therapy for patients with stubbornly high low-density lipoprotein (LDL) cholesterol has demonstrated cholesterol lowering for up to a year, in a clinical trial.
The results are from the phase 3 Recaticimab Add-On Therapy in Patients With Non-Familial Hypercholesterolemia and Mixed Hyperlipidemia (REMAIN-2) trial.
“It’s a new antibody that has a long half-life so each treatment can be prolonged,” investigator Xin Du, MD, professor of cardiology at Beijing Anzhen Hospital and the Capital Medical University, said in an interview. “Previous drugs like alirocumab and evolocumab have to be given every 2 weeks or every 4 weeks, and this new drug can be given even every 12 weeks, so it can get a very strong effect of LDL cholesterol lowering even when given every 3 months.”
Recaticimab has demonstrated a half-life of 18.6 to 27.4 days vs. 11 to 17 days for alirocumab and evolocumab, she said.
“Currently a high proportion of patients prescribed the PCSK9 inhibitors withdraw from therapy,” Dr. Du said. “After 36 months, only half of them are still on that therapy.”
Dr. Du presented the trial results at the annual scientific sessions of the American Heart Association.
Trial design and results
REMAIN-2 randomly assigned 692 patients to one of three recaticimab dosing arms vs. placebo: 150 mg/kg every 4 weeks; 300 mg/kg every 8 weeks; and 450 mg/kg every 12 weeks. The study was conducted from June 2021 to March 2023. The average age of the participants was 56 years and 64% were men. A high percentage of patients, 87% to 93.5%, completed the study across all groups. All participants had high LDL-C levels despite statin therapy: ≥ 70 mg/dL for those with cardiovascular disease and ≥ 100 mg/dL for those without.
Recaticimab enhanced LDL-C reduction by 53.4% to 62% vs. placebo at 24 weeks with a similar effect across all dosing regimens, Dr. Du said. That level of reduction was sustained out to 48 weeks, she said, at 48.4% to 64%.
At week 24, 86% to 94.5% of all patients across the three dosing arms achieved their LDL-C goal. The treatment had a positive impact on other lipid levels as well, Dr. Du said. Levels of non-HDL-C declined 55% to 47%. Apolipoprotein B (ApoB) levels fell 53% to 42% and lipoprotein (a), or Lp(a) readings declined 39.5% to 29%. The placebo arms had no change or small increases in non-HDL-C and ApoB levels and modest reductions in Lp(a).
The trial demonstrated acceptable safety and tolerability of recaticimab, Dr. Du said. At 48 weeks, the rates of injection site reactions were 3.9% in the treatment arms vs. 1.3% in the placebo arms. Common adverse events with a frequency ≥ 5% in patients receiving recaticimab were upper respiratory tract infection, hyperuricemia, urinary tract infection, increased blood creatine phosphokinase – a marker of damage to the heart – COVID-19 infection, and increased alanine transferase and aspartate transferase, both of which are markers of liver damage.
Larger, longer studies needed
Longer-term studies of recaticimab are still needed to determine its ability produce durable LDL-C reduction in a cost-effective manner, said discussant Stephen Nicholls, MD, director of Victorian Heart Institute and professor at Monash University in Australia. “It is important to note that these are still relatively short studies and the short treatment period cannot exclude the formation of neutralizing antibodies that have undermined development of other humanized antibodies,” he told attendees.
The every-12-week dosing, Dr. Nicholls said in an interview, “provides a dosing regimen that may be palatable to many patients.”
Besides the potential for the development of antibodies, Dr. Nicholls foresaw potential challenges with recaticimab. “The reality will lie in longer-term data,” he said. “If they can achieve durable lipid lowering without such neutralizing antibodies that would be very good.”
Dr. Nicholls added, “There’s a lot going on in the PCSK9 inhibitor space and the challenge for any new therapeutic, including this one, is where will it fit in given the space is getting crowded. So, data is important and clinical uptake will be equally important.”
Dr. Du disclosed relationships with Sanofi, AstraZeneca and Bayer. Dr. Nicholls disclosed relationships with AstraZeneca, Akcea, Amarin, Amgen, Anthera, Boehringer Ingelheim, Cerenis, CSL Behring, Eli Lilly, Esperion, Novartis, LipoScience, The Medicines Company, Merck, New Amsterdam Pharma, Omthera, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, Takeda, Vaxxinity, and Seqirus.
PHILADELPHIA – An investigational PCSK9 inhibitor that can be injected every 1-3 months as add-on therapy for patients with stubbornly high low-density lipoprotein (LDL) cholesterol has demonstrated cholesterol lowering for up to a year, in a clinical trial.
The results are from the phase 3 Recaticimab Add-On Therapy in Patients With Non-Familial Hypercholesterolemia and Mixed Hyperlipidemia (REMAIN-2) trial.
“It’s a new antibody that has a long half-life so each treatment can be prolonged,” investigator Xin Du, MD, professor of cardiology at Beijing Anzhen Hospital and the Capital Medical University, said in an interview. “Previous drugs like alirocumab and evolocumab have to be given every 2 weeks or every 4 weeks, and this new drug can be given even every 12 weeks, so it can get a very strong effect of LDL cholesterol lowering even when given every 3 months.”
Recaticimab has demonstrated a half-life of 18.6 to 27.4 days vs. 11 to 17 days for alirocumab and evolocumab, she said.
“Currently a high proportion of patients prescribed the PCSK9 inhibitors withdraw from therapy,” Dr. Du said. “After 36 months, only half of them are still on that therapy.”
Dr. Du presented the trial results at the annual scientific sessions of the American Heart Association.
Trial design and results
REMAIN-2 randomly assigned 692 patients to one of three recaticimab dosing arms vs. placebo: 150 mg/kg every 4 weeks; 300 mg/kg every 8 weeks; and 450 mg/kg every 12 weeks. The study was conducted from June 2021 to March 2023. The average age of the participants was 56 years and 64% were men. A high percentage of patients, 87% to 93.5%, completed the study across all groups. All participants had high LDL-C levels despite statin therapy: ≥ 70 mg/dL for those with cardiovascular disease and ≥ 100 mg/dL for those without.
Recaticimab enhanced LDL-C reduction by 53.4% to 62% vs. placebo at 24 weeks with a similar effect across all dosing regimens, Dr. Du said. That level of reduction was sustained out to 48 weeks, she said, at 48.4% to 64%.
At week 24, 86% to 94.5% of all patients across the three dosing arms achieved their LDL-C goal. The treatment had a positive impact on other lipid levels as well, Dr. Du said. Levels of non-HDL-C declined 55% to 47%. Apolipoprotein B (ApoB) levels fell 53% to 42% and lipoprotein (a), or Lp(a) readings declined 39.5% to 29%. The placebo arms had no change or small increases in non-HDL-C and ApoB levels and modest reductions in Lp(a).
The trial demonstrated acceptable safety and tolerability of recaticimab, Dr. Du said. At 48 weeks, the rates of injection site reactions were 3.9% in the treatment arms vs. 1.3% in the placebo arms. Common adverse events with a frequency ≥ 5% in patients receiving recaticimab were upper respiratory tract infection, hyperuricemia, urinary tract infection, increased blood creatine phosphokinase – a marker of damage to the heart – COVID-19 infection, and increased alanine transferase and aspartate transferase, both of which are markers of liver damage.
Larger, longer studies needed
Longer-term studies of recaticimab are still needed to determine its ability produce durable LDL-C reduction in a cost-effective manner, said discussant Stephen Nicholls, MD, director of Victorian Heart Institute and professor at Monash University in Australia. “It is important to note that these are still relatively short studies and the short treatment period cannot exclude the formation of neutralizing antibodies that have undermined development of other humanized antibodies,” he told attendees.
The every-12-week dosing, Dr. Nicholls said in an interview, “provides a dosing regimen that may be palatable to many patients.”
Besides the potential for the development of antibodies, Dr. Nicholls foresaw potential challenges with recaticimab. “The reality will lie in longer-term data,” he said. “If they can achieve durable lipid lowering without such neutralizing antibodies that would be very good.”
Dr. Nicholls added, “There’s a lot going on in the PCSK9 inhibitor space and the challenge for any new therapeutic, including this one, is where will it fit in given the space is getting crowded. So, data is important and clinical uptake will be equally important.”
Dr. Du disclosed relationships with Sanofi, AstraZeneca and Bayer. Dr. Nicholls disclosed relationships with AstraZeneca, Akcea, Amarin, Amgen, Anthera, Boehringer Ingelheim, Cerenis, CSL Behring, Eli Lilly, Esperion, Novartis, LipoScience, The Medicines Company, Merck, New Amsterdam Pharma, Omthera, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, Takeda, Vaxxinity, and Seqirus.
PHILADELPHIA – An investigational PCSK9 inhibitor that can be injected every 1-3 months as add-on therapy for patients with stubbornly high low-density lipoprotein (LDL) cholesterol has demonstrated cholesterol lowering for up to a year, in a clinical trial.
The results are from the phase 3 Recaticimab Add-On Therapy in Patients With Non-Familial Hypercholesterolemia and Mixed Hyperlipidemia (REMAIN-2) trial.
“It’s a new antibody that has a long half-life so each treatment can be prolonged,” investigator Xin Du, MD, professor of cardiology at Beijing Anzhen Hospital and the Capital Medical University, said in an interview. “Previous drugs like alirocumab and evolocumab have to be given every 2 weeks or every 4 weeks, and this new drug can be given even every 12 weeks, so it can get a very strong effect of LDL cholesterol lowering even when given every 3 months.”
Recaticimab has demonstrated a half-life of 18.6 to 27.4 days vs. 11 to 17 days for alirocumab and evolocumab, she said.
“Currently a high proportion of patients prescribed the PCSK9 inhibitors withdraw from therapy,” Dr. Du said. “After 36 months, only half of them are still on that therapy.”
Dr. Du presented the trial results at the annual scientific sessions of the American Heart Association.
Trial design and results
REMAIN-2 randomly assigned 692 patients to one of three recaticimab dosing arms vs. placebo: 150 mg/kg every 4 weeks; 300 mg/kg every 8 weeks; and 450 mg/kg every 12 weeks. The study was conducted from June 2021 to March 2023. The average age of the participants was 56 years and 64% were men. A high percentage of patients, 87% to 93.5%, completed the study across all groups. All participants had high LDL-C levels despite statin therapy: ≥ 70 mg/dL for those with cardiovascular disease and ≥ 100 mg/dL for those without.
Recaticimab enhanced LDL-C reduction by 53.4% to 62% vs. placebo at 24 weeks with a similar effect across all dosing regimens, Dr. Du said. That level of reduction was sustained out to 48 weeks, she said, at 48.4% to 64%.
At week 24, 86% to 94.5% of all patients across the three dosing arms achieved their LDL-C goal. The treatment had a positive impact on other lipid levels as well, Dr. Du said. Levels of non-HDL-C declined 55% to 47%. Apolipoprotein B (ApoB) levels fell 53% to 42% and lipoprotein (a), or Lp(a) readings declined 39.5% to 29%. The placebo arms had no change or small increases in non-HDL-C and ApoB levels and modest reductions in Lp(a).
The trial demonstrated acceptable safety and tolerability of recaticimab, Dr. Du said. At 48 weeks, the rates of injection site reactions were 3.9% in the treatment arms vs. 1.3% in the placebo arms. Common adverse events with a frequency ≥ 5% in patients receiving recaticimab were upper respiratory tract infection, hyperuricemia, urinary tract infection, increased blood creatine phosphokinase – a marker of damage to the heart – COVID-19 infection, and increased alanine transferase and aspartate transferase, both of which are markers of liver damage.
Larger, longer studies needed
Longer-term studies of recaticimab are still needed to determine its ability produce durable LDL-C reduction in a cost-effective manner, said discussant Stephen Nicholls, MD, director of Victorian Heart Institute and professor at Monash University in Australia. “It is important to note that these are still relatively short studies and the short treatment period cannot exclude the formation of neutralizing antibodies that have undermined development of other humanized antibodies,” he told attendees.
The every-12-week dosing, Dr. Nicholls said in an interview, “provides a dosing regimen that may be palatable to many patients.”
Besides the potential for the development of antibodies, Dr. Nicholls foresaw potential challenges with recaticimab. “The reality will lie in longer-term data,” he said. “If they can achieve durable lipid lowering without such neutralizing antibodies that would be very good.”
Dr. Nicholls added, “There’s a lot going on in the PCSK9 inhibitor space and the challenge for any new therapeutic, including this one, is where will it fit in given the space is getting crowded. So, data is important and clinical uptake will be equally important.”
Dr. Du disclosed relationships with Sanofi, AstraZeneca and Bayer. Dr. Nicholls disclosed relationships with AstraZeneca, Akcea, Amarin, Amgen, Anthera, Boehringer Ingelheim, Cerenis, CSL Behring, Eli Lilly, Esperion, Novartis, LipoScience, The Medicines Company, Merck, New Amsterdam Pharma, Omthera, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron, Takeda, Vaxxinity, and Seqirus.
AT AHA 2023
Cardiologists, patients can talk drug costs
PHILADELPHIA – A carefully tailored program in which physicians talked with heart failure (HF) patients about the cost of their medications improved medication adherence and the likelihood that patients get the medications they’re prescribed, results of a pilot study show.
The POCKET-COST-HF trial integrated information about patient-specific out-of-pocket (OOP) drug costs into clinical encounters between cardiologists and patients with heart failure with reduced ejection fraction (HFrEF) at six clinic sites in two different health systems. Neil W. Dickert, MD, PhD, primary investigator of the trial, said OOP costs for HFrEF patients with Medicare Part D prescription drug coverage can run upwards of $2,600 a year for four-drug therapy. Dr. Dickert is a cardiologist at Emory University in Atlanta.
“The primary outcome for the study was whether patients and clinicians essentially talked about the cost of medications,” Dr. Dickert said in an interview.
The trial, which Dr. Dickert presented at the annual scientific sessions of the American Heart Association, was designed to evaluate the effect of patient-specific OOP costs in the shared decision-making about heart failure medications, Dr. Dickert said.
The primary outcome was cost-informed decision-making, achieved in 68% of the intervention group encounters and 49% of control encounters (P = .021).
Fewer in-pharmacy adjustments
“We saw some really interesting signals of potential benefits in the space of actual decisions,” he said. “There were fewer, for example, contingency plans made in the intervention arm versus the control arm, and what that means is physicians were less likely to write a prescription and leave the decision about whether or not it’s worth it to the patient when they get to the pharmacy.”
The study intervention was a checklist of 19 heart failure medications that included OOP cost, ranging from minimal costs for generics such as diuretics and beta blockers to $617 for dapagliflozin. The checklist was based on an electronic medical records HF medications checklist. Researchers obtained drug cost estimates from TailorMed, a financial navigation company.
Six clinic sites within two health systems, one in Georgia, the other in Colorado, participated in the study. Each cluster had 40 or so patients (n = 247) randomized to the intervention or control. About two-thirds were White, a quarter were Black and 4% and 2.5% in the control and intervention group were Hispanic/LatinX. Income ranges were similar across both arms.
For the study intervention, patients got a call from the clinic 2-3 weeks before their scheduled visit to obtain verbal consent to participate and their OOP costs for drugs. The visit itself, where patients randomized to the intervention received the checklist, was audio recorded. After the visit, patients took a follow-up telephone survey, then the clinic staff did an electronic health record 3 months after the visit.
Getting the patient drug price information was not easy, Dr. Dickert said. “It required a fair amount of work and a big list to get that information that we could then populate the checklist for people,” he said. “It was a behind-the-scenes thing that is not necessarily scalable as done.”
Dr. Dickert acknowledged an increasing emphasis on price transparency in medicine, but the trade-offs are unknown. “Depending upon how that’s carried out, that can have different implications,” he said. “I’m a believer that if we think good communication has the ability to enhance medical decision-making, it also means that either bad information or bad communication can undermine.
“So, I think it’s really important to study these interventions and to do them in rigorous ways where we can really get a sense of what kind of impact they have on patients and clinicians.”
Study strengths and limitations
Discussant Dhruv Kazi, MD, director of the cardiac critical care unit at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School, both in Boston, said in an interview that this study fulfills an important function in investigating how OOP costs influence medication adherence in HFrEF patients.
“The total cost of drugs has often been a focus of policy discussions,” he said. “We talk about, how do we reduce drug costs?” He noted the Inflation Reduction Act will bring some of these drug costs down.
“On the flip side,” he added, “as a community we pay less attention to out-of-pocket costs because we assume those are not in our control, yet what the patient cares about is not the total cost of the drug, but, ‘What am I going to pay this month, and what am I going to pay cumulatively over the course of the year? Can I even afford this drug?”
POCKET-COST-HF provided a sound basis for making that investigation, he said, adding that its multisite design and mixed-methods approach – patient contact before and after visits and recording of encounters – are strengths. “Just looking at the logistics involved in pulling off something like this, the study investigators deserve to be congratulated,” he said.
One limitation, Dr. Kazi said, is its exclusion of non–English speakers. Adding them in, along with testing the intervention in community, rural, and primary care settings, are future goals for the intervention, he said. Within the trial itself, examining the cost-effectiveness of the intervention would be laudable, Dr. Kazi said.
The Agency for Healthcare Research and Quality funded the trial. Dr. Dickert disclosed relationships with Abiomed. Dr. Kazi has no relevant relationships to disclose.
PHILADELPHIA – A carefully tailored program in which physicians talked with heart failure (HF) patients about the cost of their medications improved medication adherence and the likelihood that patients get the medications they’re prescribed, results of a pilot study show.
The POCKET-COST-HF trial integrated information about patient-specific out-of-pocket (OOP) drug costs into clinical encounters between cardiologists and patients with heart failure with reduced ejection fraction (HFrEF) at six clinic sites in two different health systems. Neil W. Dickert, MD, PhD, primary investigator of the trial, said OOP costs for HFrEF patients with Medicare Part D prescription drug coverage can run upwards of $2,600 a year for four-drug therapy. Dr. Dickert is a cardiologist at Emory University in Atlanta.
“The primary outcome for the study was whether patients and clinicians essentially talked about the cost of medications,” Dr. Dickert said in an interview.
The trial, which Dr. Dickert presented at the annual scientific sessions of the American Heart Association, was designed to evaluate the effect of patient-specific OOP costs in the shared decision-making about heart failure medications, Dr. Dickert said.
The primary outcome was cost-informed decision-making, achieved in 68% of the intervention group encounters and 49% of control encounters (P = .021).
Fewer in-pharmacy adjustments
“We saw some really interesting signals of potential benefits in the space of actual decisions,” he said. “There were fewer, for example, contingency plans made in the intervention arm versus the control arm, and what that means is physicians were less likely to write a prescription and leave the decision about whether or not it’s worth it to the patient when they get to the pharmacy.”
The study intervention was a checklist of 19 heart failure medications that included OOP cost, ranging from minimal costs for generics such as diuretics and beta blockers to $617 for dapagliflozin. The checklist was based on an electronic medical records HF medications checklist. Researchers obtained drug cost estimates from TailorMed, a financial navigation company.
Six clinic sites within two health systems, one in Georgia, the other in Colorado, participated in the study. Each cluster had 40 or so patients (n = 247) randomized to the intervention or control. About two-thirds were White, a quarter were Black and 4% and 2.5% in the control and intervention group were Hispanic/LatinX. Income ranges were similar across both arms.
For the study intervention, patients got a call from the clinic 2-3 weeks before their scheduled visit to obtain verbal consent to participate and their OOP costs for drugs. The visit itself, where patients randomized to the intervention received the checklist, was audio recorded. After the visit, patients took a follow-up telephone survey, then the clinic staff did an electronic health record 3 months after the visit.
Getting the patient drug price information was not easy, Dr. Dickert said. “It required a fair amount of work and a big list to get that information that we could then populate the checklist for people,” he said. “It was a behind-the-scenes thing that is not necessarily scalable as done.”
Dr. Dickert acknowledged an increasing emphasis on price transparency in medicine, but the trade-offs are unknown. “Depending upon how that’s carried out, that can have different implications,” he said. “I’m a believer that if we think good communication has the ability to enhance medical decision-making, it also means that either bad information or bad communication can undermine.
“So, I think it’s really important to study these interventions and to do them in rigorous ways where we can really get a sense of what kind of impact they have on patients and clinicians.”
Study strengths and limitations
Discussant Dhruv Kazi, MD, director of the cardiac critical care unit at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School, both in Boston, said in an interview that this study fulfills an important function in investigating how OOP costs influence medication adherence in HFrEF patients.
“The total cost of drugs has often been a focus of policy discussions,” he said. “We talk about, how do we reduce drug costs?” He noted the Inflation Reduction Act will bring some of these drug costs down.
“On the flip side,” he added, “as a community we pay less attention to out-of-pocket costs because we assume those are not in our control, yet what the patient cares about is not the total cost of the drug, but, ‘What am I going to pay this month, and what am I going to pay cumulatively over the course of the year? Can I even afford this drug?”
POCKET-COST-HF provided a sound basis for making that investigation, he said, adding that its multisite design and mixed-methods approach – patient contact before and after visits and recording of encounters – are strengths. “Just looking at the logistics involved in pulling off something like this, the study investigators deserve to be congratulated,” he said.
One limitation, Dr. Kazi said, is its exclusion of non–English speakers. Adding them in, along with testing the intervention in community, rural, and primary care settings, are future goals for the intervention, he said. Within the trial itself, examining the cost-effectiveness of the intervention would be laudable, Dr. Kazi said.
The Agency for Healthcare Research and Quality funded the trial. Dr. Dickert disclosed relationships with Abiomed. Dr. Kazi has no relevant relationships to disclose.
PHILADELPHIA – A carefully tailored program in which physicians talked with heart failure (HF) patients about the cost of their medications improved medication adherence and the likelihood that patients get the medications they’re prescribed, results of a pilot study show.
The POCKET-COST-HF trial integrated information about patient-specific out-of-pocket (OOP) drug costs into clinical encounters between cardiologists and patients with heart failure with reduced ejection fraction (HFrEF) at six clinic sites in two different health systems. Neil W. Dickert, MD, PhD, primary investigator of the trial, said OOP costs for HFrEF patients with Medicare Part D prescription drug coverage can run upwards of $2,600 a year for four-drug therapy. Dr. Dickert is a cardiologist at Emory University in Atlanta.
“The primary outcome for the study was whether patients and clinicians essentially talked about the cost of medications,” Dr. Dickert said in an interview.
The trial, which Dr. Dickert presented at the annual scientific sessions of the American Heart Association, was designed to evaluate the effect of patient-specific OOP costs in the shared decision-making about heart failure medications, Dr. Dickert said.
The primary outcome was cost-informed decision-making, achieved in 68% of the intervention group encounters and 49% of control encounters (P = .021).
Fewer in-pharmacy adjustments
“We saw some really interesting signals of potential benefits in the space of actual decisions,” he said. “There were fewer, for example, contingency plans made in the intervention arm versus the control arm, and what that means is physicians were less likely to write a prescription and leave the decision about whether or not it’s worth it to the patient when they get to the pharmacy.”
The study intervention was a checklist of 19 heart failure medications that included OOP cost, ranging from minimal costs for generics such as diuretics and beta blockers to $617 for dapagliflozin. The checklist was based on an electronic medical records HF medications checklist. Researchers obtained drug cost estimates from TailorMed, a financial navigation company.
Six clinic sites within two health systems, one in Georgia, the other in Colorado, participated in the study. Each cluster had 40 or so patients (n = 247) randomized to the intervention or control. About two-thirds were White, a quarter were Black and 4% and 2.5% in the control and intervention group were Hispanic/LatinX. Income ranges were similar across both arms.
For the study intervention, patients got a call from the clinic 2-3 weeks before their scheduled visit to obtain verbal consent to participate and their OOP costs for drugs. The visit itself, where patients randomized to the intervention received the checklist, was audio recorded. After the visit, patients took a follow-up telephone survey, then the clinic staff did an electronic health record 3 months after the visit.
Getting the patient drug price information was not easy, Dr. Dickert said. “It required a fair amount of work and a big list to get that information that we could then populate the checklist for people,” he said. “It was a behind-the-scenes thing that is not necessarily scalable as done.”
Dr. Dickert acknowledged an increasing emphasis on price transparency in medicine, but the trade-offs are unknown. “Depending upon how that’s carried out, that can have different implications,” he said. “I’m a believer that if we think good communication has the ability to enhance medical decision-making, it also means that either bad information or bad communication can undermine.
“So, I think it’s really important to study these interventions and to do them in rigorous ways where we can really get a sense of what kind of impact they have on patients and clinicians.”
Study strengths and limitations
Discussant Dhruv Kazi, MD, director of the cardiac critical care unit at Beth Israel Deaconess Medical Center and associate professor at Harvard Medical School, both in Boston, said in an interview that this study fulfills an important function in investigating how OOP costs influence medication adherence in HFrEF patients.
“The total cost of drugs has often been a focus of policy discussions,” he said. “We talk about, how do we reduce drug costs?” He noted the Inflation Reduction Act will bring some of these drug costs down.
“On the flip side,” he added, “as a community we pay less attention to out-of-pocket costs because we assume those are not in our control, yet what the patient cares about is not the total cost of the drug, but, ‘What am I going to pay this month, and what am I going to pay cumulatively over the course of the year? Can I even afford this drug?”
POCKET-COST-HF provided a sound basis for making that investigation, he said, adding that its multisite design and mixed-methods approach – patient contact before and after visits and recording of encounters – are strengths. “Just looking at the logistics involved in pulling off something like this, the study investigators deserve to be congratulated,” he said.
One limitation, Dr. Kazi said, is its exclusion of non–English speakers. Adding them in, along with testing the intervention in community, rural, and primary care settings, are future goals for the intervention, he said. Within the trial itself, examining the cost-effectiveness of the intervention would be laudable, Dr. Kazi said.
The Agency for Healthcare Research and Quality funded the trial. Dr. Dickert disclosed relationships with Abiomed. Dr. Kazi has no relevant relationships to disclose.
AT AHA 2023
Promising first results with DNA editing to lower LDL
PHILADELPHIA –
While one of four patients in the highest-dose groups had a myocardial infarction the day after getting the treatment, investigators have enough confidence to go forward with the next phase of study.
“The HEART-1trial demonstrated the first human proof of concept for in vivo DNA-based editing,” said Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, the company developing the treatment. “We saw dose-dependent–based reductions in LDL and the PCSK9 protein.”
The HEART-1 study was a phase 1b trial of VERVE-101, a CRISPR-based gene editing mechanism designed to inactivate the liver gene PCSK9, which contributes to raising cholesterol. “Human genetics suggest that turning off the cholesterol-raising gene PCSK9 in the liver will durably reduce LDL cholesterol,” Dr. Bellinger said in presenting the results at the annual scientific sessions of the American Heart Association.
Lipid nanoparticle
VERVE-101 is designed to be a single-course treatment to specifically treat HeFH, Dr. Bellinger said. He explained how the therapy, given by intravenous infusion, differs from adeno-associated virus vectors that have dominated gene therapy platforms.
“It’s a lipid nanoparticle encapsulating two RNA nanoparticles that are taken up by hepatocytes in the liver from the blood by the LDL receptor,” he explained. “Then the A-to-G–based editor protein and the guide mRNA protein together find the PCSK9 gene in the liver.” That single DNA-base change in one position of the PCSK9 gene is able to turn off PCSK9 production in those liver cells.
Dr. Bellinger presented interim results of the first 10 patients treated in the open-label, single ascending dose study. The patients were male and female, ages 18-75, with HeFH, established atherosclerotic cardiovascular disease and uncontrolled hypercholesterolemia despite being on maximally tolerated lipid-lowering therapy.
They received four different doses: Three patients each received 0.1, 0.3, and 0.45 mg/kg; and one patient received 0.6 mg/kg.
Reductions in blood PCSK9 levels were measured across all dosing groups at 4 weeks, but they were most pronounced in the two highest groups, Dr. Bellinger said. Two patients in the 0.45-mg/kg group had reductions of 59% and 84%. The sole patient in the 0.6-mg/kg arm had a reduction of 47%.
Regarding the 84% reduction in one individual, Dr. Bellinger said, “Roughly 85% of PCSK9 comes from the liver. These data suggest that we have successfully made a single base pair change in both copies of the PCSK9 gene in nearly every hepatocyte in the liver of this individual.”
Those benefits carried over to LDL cholesterol measures, with the highest-dose patients registering 39%, 48% and 55% reductions.
Safety outcomes
Two patients had serious cardiovascular (CV) events. One in the 0.3-mg/kg arm died from cardiac arrest 5 weeks after receiving the infusion. A patient in the 0.45-mg/kg arm had a myocardial infarction a day after getting the infusion and then nonsustained ventricular tachycardia (NSVT) 4 weeks later. Dr. Bellinger said an independent review panel determined that the CV events were in line with outcomes for high-risk patients and weren’t directly related to treatment.
He added, “Increased liver transaminases were seen in patients treated in the higher-dose cohorts. It’s transient, asymptomatic, and it resolved quickly.”
The next step involves pursuing only the 0.45- and 0.6-mg/kg doses in the next dose-escalation phase and enrolling an expansion cohort in 2024, Dr. Bellinger said, with a plan to initiate a randomized, placebo-controlled phase 2 trial in 2025.
First, do no harm
Karol Watson, MD, PhD, a women’s cardiovascular disease specialist at UCLA, said the promise of gene therapy was “revolutionary,” but that proving safety was critical going forward.
“You’re changing the genome forever,” she said. “Safety is going to be of the utmost importance especially because there are currently safe and efficacious strategies available for lipid lowering. This is a strategy that could be revolutionary, but we have to make sure that it’s safe.”
She pointed to a multinational study from earlier this year that warned about pathogenic consequences from CRISPR-based gene editing. “There are concerns about gene editing,” Dr. Watson said. “This was a whole-genome analysis showing atypical nonhomologous on-target effects of genome editing. Of course this is a very different strategy from what we heard today, but, again, we have to know that this is safe.”
Despite the small sample size from the two highest-dose groups in the study, Dr. Watson said the investigators have reason for going forward. “I think the preclinical data supports moving forward, but the next studies will have to be scrutinized carefully,” she said. “This is a preventive therapy; the first tenet is to do no harm.”
Dr. Bellinger is an employee of Verve Therapeutics, which sponsored the trial. Dr. Watson disclosed relationships with Boehringer-Ingelheim, Amgen, Lilly and Novartis.
PHILADELPHIA –
While one of four patients in the highest-dose groups had a myocardial infarction the day after getting the treatment, investigators have enough confidence to go forward with the next phase of study.
“The HEART-1trial demonstrated the first human proof of concept for in vivo DNA-based editing,” said Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, the company developing the treatment. “We saw dose-dependent–based reductions in LDL and the PCSK9 protein.”
The HEART-1 study was a phase 1b trial of VERVE-101, a CRISPR-based gene editing mechanism designed to inactivate the liver gene PCSK9, which contributes to raising cholesterol. “Human genetics suggest that turning off the cholesterol-raising gene PCSK9 in the liver will durably reduce LDL cholesterol,” Dr. Bellinger said in presenting the results at the annual scientific sessions of the American Heart Association.
Lipid nanoparticle
VERVE-101 is designed to be a single-course treatment to specifically treat HeFH, Dr. Bellinger said. He explained how the therapy, given by intravenous infusion, differs from adeno-associated virus vectors that have dominated gene therapy platforms.
“It’s a lipid nanoparticle encapsulating two RNA nanoparticles that are taken up by hepatocytes in the liver from the blood by the LDL receptor,” he explained. “Then the A-to-G–based editor protein and the guide mRNA protein together find the PCSK9 gene in the liver.” That single DNA-base change in one position of the PCSK9 gene is able to turn off PCSK9 production in those liver cells.
Dr. Bellinger presented interim results of the first 10 patients treated in the open-label, single ascending dose study. The patients were male and female, ages 18-75, with HeFH, established atherosclerotic cardiovascular disease and uncontrolled hypercholesterolemia despite being on maximally tolerated lipid-lowering therapy.
They received four different doses: Three patients each received 0.1, 0.3, and 0.45 mg/kg; and one patient received 0.6 mg/kg.
Reductions in blood PCSK9 levels were measured across all dosing groups at 4 weeks, but they were most pronounced in the two highest groups, Dr. Bellinger said. Two patients in the 0.45-mg/kg group had reductions of 59% and 84%. The sole patient in the 0.6-mg/kg arm had a reduction of 47%.
Regarding the 84% reduction in one individual, Dr. Bellinger said, “Roughly 85% of PCSK9 comes from the liver. These data suggest that we have successfully made a single base pair change in both copies of the PCSK9 gene in nearly every hepatocyte in the liver of this individual.”
Those benefits carried over to LDL cholesterol measures, with the highest-dose patients registering 39%, 48% and 55% reductions.
Safety outcomes
Two patients had serious cardiovascular (CV) events. One in the 0.3-mg/kg arm died from cardiac arrest 5 weeks after receiving the infusion. A patient in the 0.45-mg/kg arm had a myocardial infarction a day after getting the infusion and then nonsustained ventricular tachycardia (NSVT) 4 weeks later. Dr. Bellinger said an independent review panel determined that the CV events were in line with outcomes for high-risk patients and weren’t directly related to treatment.
He added, “Increased liver transaminases were seen in patients treated in the higher-dose cohorts. It’s transient, asymptomatic, and it resolved quickly.”
The next step involves pursuing only the 0.45- and 0.6-mg/kg doses in the next dose-escalation phase and enrolling an expansion cohort in 2024, Dr. Bellinger said, with a plan to initiate a randomized, placebo-controlled phase 2 trial in 2025.
First, do no harm
Karol Watson, MD, PhD, a women’s cardiovascular disease specialist at UCLA, said the promise of gene therapy was “revolutionary,” but that proving safety was critical going forward.
“You’re changing the genome forever,” she said. “Safety is going to be of the utmost importance especially because there are currently safe and efficacious strategies available for lipid lowering. This is a strategy that could be revolutionary, but we have to make sure that it’s safe.”
She pointed to a multinational study from earlier this year that warned about pathogenic consequences from CRISPR-based gene editing. “There are concerns about gene editing,” Dr. Watson said. “This was a whole-genome analysis showing atypical nonhomologous on-target effects of genome editing. Of course this is a very different strategy from what we heard today, but, again, we have to know that this is safe.”
Despite the small sample size from the two highest-dose groups in the study, Dr. Watson said the investigators have reason for going forward. “I think the preclinical data supports moving forward, but the next studies will have to be scrutinized carefully,” she said. “This is a preventive therapy; the first tenet is to do no harm.”
Dr. Bellinger is an employee of Verve Therapeutics, which sponsored the trial. Dr. Watson disclosed relationships with Boehringer-Ingelheim, Amgen, Lilly and Novartis.
PHILADELPHIA –
While one of four patients in the highest-dose groups had a myocardial infarction the day after getting the treatment, investigators have enough confidence to go forward with the next phase of study.
“The HEART-1trial demonstrated the first human proof of concept for in vivo DNA-based editing,” said Andrew Bellinger, MD, PhD, chief scientific officer of Verve Therapeutics, the company developing the treatment. “We saw dose-dependent–based reductions in LDL and the PCSK9 protein.”
The HEART-1 study was a phase 1b trial of VERVE-101, a CRISPR-based gene editing mechanism designed to inactivate the liver gene PCSK9, which contributes to raising cholesterol. “Human genetics suggest that turning off the cholesterol-raising gene PCSK9 in the liver will durably reduce LDL cholesterol,” Dr. Bellinger said in presenting the results at the annual scientific sessions of the American Heart Association.
Lipid nanoparticle
VERVE-101 is designed to be a single-course treatment to specifically treat HeFH, Dr. Bellinger said. He explained how the therapy, given by intravenous infusion, differs from adeno-associated virus vectors that have dominated gene therapy platforms.
“It’s a lipid nanoparticle encapsulating two RNA nanoparticles that are taken up by hepatocytes in the liver from the blood by the LDL receptor,” he explained. “Then the A-to-G–based editor protein and the guide mRNA protein together find the PCSK9 gene in the liver.” That single DNA-base change in one position of the PCSK9 gene is able to turn off PCSK9 production in those liver cells.
Dr. Bellinger presented interim results of the first 10 patients treated in the open-label, single ascending dose study. The patients were male and female, ages 18-75, with HeFH, established atherosclerotic cardiovascular disease and uncontrolled hypercholesterolemia despite being on maximally tolerated lipid-lowering therapy.
They received four different doses: Three patients each received 0.1, 0.3, and 0.45 mg/kg; and one patient received 0.6 mg/kg.
Reductions in blood PCSK9 levels were measured across all dosing groups at 4 weeks, but they were most pronounced in the two highest groups, Dr. Bellinger said. Two patients in the 0.45-mg/kg group had reductions of 59% and 84%. The sole patient in the 0.6-mg/kg arm had a reduction of 47%.
Regarding the 84% reduction in one individual, Dr. Bellinger said, “Roughly 85% of PCSK9 comes from the liver. These data suggest that we have successfully made a single base pair change in both copies of the PCSK9 gene in nearly every hepatocyte in the liver of this individual.”
Those benefits carried over to LDL cholesterol measures, with the highest-dose patients registering 39%, 48% and 55% reductions.
Safety outcomes
Two patients had serious cardiovascular (CV) events. One in the 0.3-mg/kg arm died from cardiac arrest 5 weeks after receiving the infusion. A patient in the 0.45-mg/kg arm had a myocardial infarction a day after getting the infusion and then nonsustained ventricular tachycardia (NSVT) 4 weeks later. Dr. Bellinger said an independent review panel determined that the CV events were in line with outcomes for high-risk patients and weren’t directly related to treatment.
He added, “Increased liver transaminases were seen in patients treated in the higher-dose cohorts. It’s transient, asymptomatic, and it resolved quickly.”
The next step involves pursuing only the 0.45- and 0.6-mg/kg doses in the next dose-escalation phase and enrolling an expansion cohort in 2024, Dr. Bellinger said, with a plan to initiate a randomized, placebo-controlled phase 2 trial in 2025.
First, do no harm
Karol Watson, MD, PhD, a women’s cardiovascular disease specialist at UCLA, said the promise of gene therapy was “revolutionary,” but that proving safety was critical going forward.
“You’re changing the genome forever,” she said. “Safety is going to be of the utmost importance especially because there are currently safe and efficacious strategies available for lipid lowering. This is a strategy that could be revolutionary, but we have to make sure that it’s safe.”
She pointed to a multinational study from earlier this year that warned about pathogenic consequences from CRISPR-based gene editing. “There are concerns about gene editing,” Dr. Watson said. “This was a whole-genome analysis showing atypical nonhomologous on-target effects of genome editing. Of course this is a very different strategy from what we heard today, but, again, we have to know that this is safe.”
Despite the small sample size from the two highest-dose groups in the study, Dr. Watson said the investigators have reason for going forward. “I think the preclinical data supports moving forward, but the next studies will have to be scrutinized carefully,” she said. “This is a preventive therapy; the first tenet is to do no harm.”
Dr. Bellinger is an employee of Verve Therapeutics, which sponsored the trial. Dr. Watson disclosed relationships with Boehringer-Ingelheim, Amgen, Lilly and Novartis.
AT AHA 2023
AI-ECG gets STEMI patients to cath lab sooner
PHILADELPHIA – An artificial intelligence platform that sends alerts based on electrocardiography results enabled cardiologists and emergency department physicians at a major hospital in Taiwan to move patients with ST-elevation myocardial infarction (STEMI) into the catheterization laboratory 9 minutes sooner than the conventional protocol that did not use AI.
“This is the first randomized clinical trial to demonstrate the reduction of electrocardiography to coronary cath lab activation time" from 52.3 to 43.3 minutes (P = .003), Chin Sheng Lin, MD, PhD, director of cardiology at the National Defense Medical Center Tri-Service General Hospital in Taipei City, said in presenting the results at the American Heart Association scientific sessions.
Dr. Lin reported results from the Artificial Intelligence Enabled Rapid Identify of ST-Elevation Myocardial Infarction Using Electrocardiogram (ARISE) trial. The trial included 43,994 patients who came to the hospital’s emergency and inpatient departments with at least one ECG but no history of coronary angiography (CAG) in the previous 3 days between May 2022 and April 2023.
They were randomly assigned by date to either AI-ECG for rapid identification and triage of STEMI or standard care. Overall, 145 patients were finally diagnosed with STEMI based on CAG, 77 in the intervention group and 68 in the control group. All patients were seen by one of 20 cardiologists who participated in the study.
Dr. Lin and his group developed an AI algorithm that captures the ECG readout in the emergency department, analyzes the data and then sends a high-risk alarm to the front-line physician and on-duty cardiologist to activate the primary percutaneous coronary intervention (PCI).
Trial results
The differentiation between groups was even more pronounced in ED patients during regular working hours, Dr. Lin said, at 61.6 minutes for the intervention group vs. 33.1 minutes for controls (P = .001).*
He noted that the AI group showed a trend towards fewer cases of clinically suspected STEMI but not getting CAG, 6.5% vs. 15.8%, for an odds ratio of 0.37 (95% confidence interval, 0.14-0.94).
The AI-ECG model also demonstrated a high diagnostic accuracy. “With this AI-ECG system, because it has a very high accuracy and a high positive predictive variable that reach 88%, we can send a message to the on-duty cardiologists and also the emergency room physician and they can send the patients to receive the operation or the PCI as soon as possible,” Dr. Lin said in an interview.
The time differential is critical, Dr. Lin said. “For the patient with acute myocardial infarction, 1 minute is critical, because the patients can die within minutes,” he said. “If we can save 9 minutes I think we can save more lives, but it needs a larger study to evaluate that.”
Dr. Lin acknowledged a few limitations with the trial, among them its single-center nature, relatively small sample size of STEMI patients and the short-term of follow-up. Future study should involve multiple centers along with a prehospital, emergency medical services AI-ECG model.
‘Novel’ for an AI trial
“This is an incredible application of an AI technology in a real-world problem,” said Brahmajee K. Nallamothu, MD, MPH, an interventional cardiologist at the University of Michigan, Ann Arbor, who did not participate in the study. “What I really love about this study is it’s actually a clinical problem that has large implications, particularly for under-resourced areas.”
Using a randomized clinical trial to evaluate the AI platform is “very, very novel,” he said, and called the time improvement “enormous.” Referencing Dr. Lin’s next steps for studying the AI-ECG platform, Dr. Nallamothu said, “if we could push this up even earlier to paramedics and EMTs and prehospital systems, there would be a lot of excitement there.”
He noted the sensitivity analysis resulted in a rate of 88.8% along with the positive predictive value of 88%. “Missing 1 out of 10 ST-elevation MIs in my eyes can still be considered a big deal, so we need to know if this is happening in particular types of patients, for example women versus men, or other groups.”
However, some investigations reported false activation rates as high as 33%, he said. “So, to say that, the positive predictive value is at 88% is really exciting and I think it can make a real inroads,” Dr. Nallamothu said.
Dr. Lin and Dr. Nallamothu have no relevant disclosures.
*Correction, 11/20/23: An earlier version of this article misstated in both trial arms the time to coronary catheterization lab activation.
PHILADELPHIA – An artificial intelligence platform that sends alerts based on electrocardiography results enabled cardiologists and emergency department physicians at a major hospital in Taiwan to move patients with ST-elevation myocardial infarction (STEMI) into the catheterization laboratory 9 minutes sooner than the conventional protocol that did not use AI.
“This is the first randomized clinical trial to demonstrate the reduction of electrocardiography to coronary cath lab activation time" from 52.3 to 43.3 minutes (P = .003), Chin Sheng Lin, MD, PhD, director of cardiology at the National Defense Medical Center Tri-Service General Hospital in Taipei City, said in presenting the results at the American Heart Association scientific sessions.
Dr. Lin reported results from the Artificial Intelligence Enabled Rapid Identify of ST-Elevation Myocardial Infarction Using Electrocardiogram (ARISE) trial. The trial included 43,994 patients who came to the hospital’s emergency and inpatient departments with at least one ECG but no history of coronary angiography (CAG) in the previous 3 days between May 2022 and April 2023.
They were randomly assigned by date to either AI-ECG for rapid identification and triage of STEMI or standard care. Overall, 145 patients were finally diagnosed with STEMI based on CAG, 77 in the intervention group and 68 in the control group. All patients were seen by one of 20 cardiologists who participated in the study.
Dr. Lin and his group developed an AI algorithm that captures the ECG readout in the emergency department, analyzes the data and then sends a high-risk alarm to the front-line physician and on-duty cardiologist to activate the primary percutaneous coronary intervention (PCI).
Trial results
The differentiation between groups was even more pronounced in ED patients during regular working hours, Dr. Lin said, at 61.6 minutes for the intervention group vs. 33.1 minutes for controls (P = .001).*
He noted that the AI group showed a trend towards fewer cases of clinically suspected STEMI but not getting CAG, 6.5% vs. 15.8%, for an odds ratio of 0.37 (95% confidence interval, 0.14-0.94).
The AI-ECG model also demonstrated a high diagnostic accuracy. “With this AI-ECG system, because it has a very high accuracy and a high positive predictive variable that reach 88%, we can send a message to the on-duty cardiologists and also the emergency room physician and they can send the patients to receive the operation or the PCI as soon as possible,” Dr. Lin said in an interview.
The time differential is critical, Dr. Lin said. “For the patient with acute myocardial infarction, 1 minute is critical, because the patients can die within minutes,” he said. “If we can save 9 minutes I think we can save more lives, but it needs a larger study to evaluate that.”
Dr. Lin acknowledged a few limitations with the trial, among them its single-center nature, relatively small sample size of STEMI patients and the short-term of follow-up. Future study should involve multiple centers along with a prehospital, emergency medical services AI-ECG model.
‘Novel’ for an AI trial
“This is an incredible application of an AI technology in a real-world problem,” said Brahmajee K. Nallamothu, MD, MPH, an interventional cardiologist at the University of Michigan, Ann Arbor, who did not participate in the study. “What I really love about this study is it’s actually a clinical problem that has large implications, particularly for under-resourced areas.”
Using a randomized clinical trial to evaluate the AI platform is “very, very novel,” he said, and called the time improvement “enormous.” Referencing Dr. Lin’s next steps for studying the AI-ECG platform, Dr. Nallamothu said, “if we could push this up even earlier to paramedics and EMTs and prehospital systems, there would be a lot of excitement there.”
He noted the sensitivity analysis resulted in a rate of 88.8% along with the positive predictive value of 88%. “Missing 1 out of 10 ST-elevation MIs in my eyes can still be considered a big deal, so we need to know if this is happening in particular types of patients, for example women versus men, or other groups.”
However, some investigations reported false activation rates as high as 33%, he said. “So, to say that, the positive predictive value is at 88% is really exciting and I think it can make a real inroads,” Dr. Nallamothu said.
Dr. Lin and Dr. Nallamothu have no relevant disclosures.
*Correction, 11/20/23: An earlier version of this article misstated in both trial arms the time to coronary catheterization lab activation.
PHILADELPHIA – An artificial intelligence platform that sends alerts based on electrocardiography results enabled cardiologists and emergency department physicians at a major hospital in Taiwan to move patients with ST-elevation myocardial infarction (STEMI) into the catheterization laboratory 9 minutes sooner than the conventional protocol that did not use AI.
“This is the first randomized clinical trial to demonstrate the reduction of electrocardiography to coronary cath lab activation time" from 52.3 to 43.3 minutes (P = .003), Chin Sheng Lin, MD, PhD, director of cardiology at the National Defense Medical Center Tri-Service General Hospital in Taipei City, said in presenting the results at the American Heart Association scientific sessions.
Dr. Lin reported results from the Artificial Intelligence Enabled Rapid Identify of ST-Elevation Myocardial Infarction Using Electrocardiogram (ARISE) trial. The trial included 43,994 patients who came to the hospital’s emergency and inpatient departments with at least one ECG but no history of coronary angiography (CAG) in the previous 3 days between May 2022 and April 2023.
They were randomly assigned by date to either AI-ECG for rapid identification and triage of STEMI or standard care. Overall, 145 patients were finally diagnosed with STEMI based on CAG, 77 in the intervention group and 68 in the control group. All patients were seen by one of 20 cardiologists who participated in the study.
Dr. Lin and his group developed an AI algorithm that captures the ECG readout in the emergency department, analyzes the data and then sends a high-risk alarm to the front-line physician and on-duty cardiologist to activate the primary percutaneous coronary intervention (PCI).
Trial results
The differentiation between groups was even more pronounced in ED patients during regular working hours, Dr. Lin said, at 61.6 minutes for the intervention group vs. 33.1 minutes for controls (P = .001).*
He noted that the AI group showed a trend towards fewer cases of clinically suspected STEMI but not getting CAG, 6.5% vs. 15.8%, for an odds ratio of 0.37 (95% confidence interval, 0.14-0.94).
The AI-ECG model also demonstrated a high diagnostic accuracy. “With this AI-ECG system, because it has a very high accuracy and a high positive predictive variable that reach 88%, we can send a message to the on-duty cardiologists and also the emergency room physician and they can send the patients to receive the operation or the PCI as soon as possible,” Dr. Lin said in an interview.
The time differential is critical, Dr. Lin said. “For the patient with acute myocardial infarction, 1 minute is critical, because the patients can die within minutes,” he said. “If we can save 9 minutes I think we can save more lives, but it needs a larger study to evaluate that.”
Dr. Lin acknowledged a few limitations with the trial, among them its single-center nature, relatively small sample size of STEMI patients and the short-term of follow-up. Future study should involve multiple centers along with a prehospital, emergency medical services AI-ECG model.
‘Novel’ for an AI trial
“This is an incredible application of an AI technology in a real-world problem,” said Brahmajee K. Nallamothu, MD, MPH, an interventional cardiologist at the University of Michigan, Ann Arbor, who did not participate in the study. “What I really love about this study is it’s actually a clinical problem that has large implications, particularly for under-resourced areas.”
Using a randomized clinical trial to evaluate the AI platform is “very, very novel,” he said, and called the time improvement “enormous.” Referencing Dr. Lin’s next steps for studying the AI-ECG platform, Dr. Nallamothu said, “if we could push this up even earlier to paramedics and EMTs and prehospital systems, there would be a lot of excitement there.”
He noted the sensitivity analysis resulted in a rate of 88.8% along with the positive predictive value of 88%. “Missing 1 out of 10 ST-elevation MIs in my eyes can still be considered a big deal, so we need to know if this is happening in particular types of patients, for example women versus men, or other groups.”
However, some investigations reported false activation rates as high as 33%, he said. “So, to say that, the positive predictive value is at 88% is really exciting and I think it can make a real inroads,” Dr. Nallamothu said.
Dr. Lin and Dr. Nallamothu have no relevant disclosures.
*Correction, 11/20/23: An earlier version of this article misstated in both trial arms the time to coronary catheterization lab activation.
AT AHA 2023
GLP-1s don’t appear to worsen diabetic retinopathy
SAN FRANCISCO – A large observational registry study of almost 100,000 eyes has found that the diabetes drug semaglutide, a GLP-1 agonist recently approved for weight loss, does not worsen the progression of potentially vision-threatening diabetic retinopathy in the long term in patients taking the drug. However, the researchers said, the findings do not obviate the need for providers to have a conversation about the potential risks to vision posed by the drug.
“In patients that have either no or early or relatively nonadvanced diabetic retinopathy, the absolute risk of having a worsening in their retinopathy is variable,” Zeeshan Haq, MD, a retina specialist at Retinal Consultants of Minnesota, told this news organization. Dr. Hag presented the findings Nov. 3 at the annual meeting of the American Academy of Ophthalmology.
“Based on this preliminary evidence and what we know so far, it suggests that there is a risk of worsening, but it’s quite low for most patients, and so a conversation needs to be had between anyone considering prescribing the drug, such as a general practitioner or a nurse practitioner, and that patient’s optometrist or comprehensive ophthalmologist or retina specialist.”
Methodology and results
Dr. Haq reported on a retrospective case series of 96,462 eyes from the Intelligent Research in Sight (IRIS) registry. Patients had type 2 diabetes and began taking injectable semaglutide between January 2013 and December 2021.
The study evaluated eyes with three levels of retinopathy:
- No retinopathy or background retinopathy (71.8%).
- Mild or moderate nonproliferative diabetic retinopathy (NPDR) (18.4%).
- Severe NPDR or proliferative diabetic retinopathy (PDR) (9.8%).
In eyes with no or background retinopathy, 1.3%, 1.2%, 1.6%, and 2.2% experienced a worsening in status of the condition at 3, 6, 12, and 24 months, respectively.
In eyes with mild or moderate NPDR, 2.4%, 3%, 3.4%, and 3.5% showed worsening retinopathy at the respective time intervals.
Improvement of retinopathy rather than worsening was evaluated in the eyes with severe NPDR or PDR. At 3, 6, 12, and 24 months, improvement was observed in 40%, 37.8%, 47.7%, and 58.7% of these eyes, respectively.
Most patients were aged 51-75 years (77.2%), female (55.0%), and White (63.8%).
The study found low rates of the following complications across the same time intervals: vitreous hemorrhage (from 0.1% to 0.15%); traction retinal detachment (0.02% to 0.05%); and neovascular glaucoma (0.03% to –0.04%), Dr. Haq reported.
Dr. Haq noted that understanding the possible consequences that semaglutide has on vision is important as the drug becomes more widely available for both diabetes and weight control. The Centers for Disease Control and Prevention reports that 37.3 million people in the United States have diabetes; 28.7 million cases have been diagnosed, and 8.5 million are undiagnosed.
Clinical implications
“Any patient in the United States with diabetes has to undergo screening for diabetic eye disease, and so they’re usually plugged into the eye-care system,” Dr. Haq said. “But if they’re going to be starting this drug and they don’t have any existing diabetic retinopathy, the discussion should be had between their doctor and the eye-care provider, and if they do have a history of DR, an evaluation with the eye-care provider should probably happen upon starting the drug.”
Vaidehi Dedania, MD, a retina specialist at NYU Langone Health in New York, said the findings underscore the importance of counseling patients who are taking semaglutide about potential vision outcomes.
“We know that when patients get rapid control of their diabetes, their diabetic retinopathy can worsen in the short term, although it always ends up doing better in long term anyway,” Dr. Dedania said in an interview. “We always educate our patients that if they get control of the diabetes to not feel discouraged if their diabetic retinopathy worsens despite getting good control, because we know in the long run it always get better.”
The new findings, however, may have masked some worsening of retinopathy because of how the researchers categorized the condition. “It’s hard to assess changes within a designation because they’re so broad,” Dr. Dedania said.
She also noted potential limitations with the IRIS database itself. “The data collected from it are not always as complete as you might need for the purpose of understanding this, so that’s a limitation,” she said. While the high number of patients is a strength of the study, she added, “I still think the limitations are pretty significant.”
Dr. Haq has disclosed no relevant financial relationships. Dr. Dedania has relationships with Genentech/Roche and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – A large observational registry study of almost 100,000 eyes has found that the diabetes drug semaglutide, a GLP-1 agonist recently approved for weight loss, does not worsen the progression of potentially vision-threatening diabetic retinopathy in the long term in patients taking the drug. However, the researchers said, the findings do not obviate the need for providers to have a conversation about the potential risks to vision posed by the drug.
“In patients that have either no or early or relatively nonadvanced diabetic retinopathy, the absolute risk of having a worsening in their retinopathy is variable,” Zeeshan Haq, MD, a retina specialist at Retinal Consultants of Minnesota, told this news organization. Dr. Hag presented the findings Nov. 3 at the annual meeting of the American Academy of Ophthalmology.
“Based on this preliminary evidence and what we know so far, it suggests that there is a risk of worsening, but it’s quite low for most patients, and so a conversation needs to be had between anyone considering prescribing the drug, such as a general practitioner or a nurse practitioner, and that patient’s optometrist or comprehensive ophthalmologist or retina specialist.”
Methodology and results
Dr. Haq reported on a retrospective case series of 96,462 eyes from the Intelligent Research in Sight (IRIS) registry. Patients had type 2 diabetes and began taking injectable semaglutide between January 2013 and December 2021.
The study evaluated eyes with three levels of retinopathy:
- No retinopathy or background retinopathy (71.8%).
- Mild or moderate nonproliferative diabetic retinopathy (NPDR) (18.4%).
- Severe NPDR or proliferative diabetic retinopathy (PDR) (9.8%).
In eyes with no or background retinopathy, 1.3%, 1.2%, 1.6%, and 2.2% experienced a worsening in status of the condition at 3, 6, 12, and 24 months, respectively.
In eyes with mild or moderate NPDR, 2.4%, 3%, 3.4%, and 3.5% showed worsening retinopathy at the respective time intervals.
Improvement of retinopathy rather than worsening was evaluated in the eyes with severe NPDR or PDR. At 3, 6, 12, and 24 months, improvement was observed in 40%, 37.8%, 47.7%, and 58.7% of these eyes, respectively.
Most patients were aged 51-75 years (77.2%), female (55.0%), and White (63.8%).
The study found low rates of the following complications across the same time intervals: vitreous hemorrhage (from 0.1% to 0.15%); traction retinal detachment (0.02% to 0.05%); and neovascular glaucoma (0.03% to –0.04%), Dr. Haq reported.
Dr. Haq noted that understanding the possible consequences that semaglutide has on vision is important as the drug becomes more widely available for both diabetes and weight control. The Centers for Disease Control and Prevention reports that 37.3 million people in the United States have diabetes; 28.7 million cases have been diagnosed, and 8.5 million are undiagnosed.
Clinical implications
“Any patient in the United States with diabetes has to undergo screening for diabetic eye disease, and so they’re usually plugged into the eye-care system,” Dr. Haq said. “But if they’re going to be starting this drug and they don’t have any existing diabetic retinopathy, the discussion should be had between their doctor and the eye-care provider, and if they do have a history of DR, an evaluation with the eye-care provider should probably happen upon starting the drug.”
Vaidehi Dedania, MD, a retina specialist at NYU Langone Health in New York, said the findings underscore the importance of counseling patients who are taking semaglutide about potential vision outcomes.
“We know that when patients get rapid control of their diabetes, their diabetic retinopathy can worsen in the short term, although it always ends up doing better in long term anyway,” Dr. Dedania said in an interview. “We always educate our patients that if they get control of the diabetes to not feel discouraged if their diabetic retinopathy worsens despite getting good control, because we know in the long run it always get better.”
The new findings, however, may have masked some worsening of retinopathy because of how the researchers categorized the condition. “It’s hard to assess changes within a designation because they’re so broad,” Dr. Dedania said.
She also noted potential limitations with the IRIS database itself. “The data collected from it are not always as complete as you might need for the purpose of understanding this, so that’s a limitation,” she said. While the high number of patients is a strength of the study, she added, “I still think the limitations are pretty significant.”
Dr. Haq has disclosed no relevant financial relationships. Dr. Dedania has relationships with Genentech/Roche and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
SAN FRANCISCO – A large observational registry study of almost 100,000 eyes has found that the diabetes drug semaglutide, a GLP-1 agonist recently approved for weight loss, does not worsen the progression of potentially vision-threatening diabetic retinopathy in the long term in patients taking the drug. However, the researchers said, the findings do not obviate the need for providers to have a conversation about the potential risks to vision posed by the drug.
“In patients that have either no or early or relatively nonadvanced diabetic retinopathy, the absolute risk of having a worsening in their retinopathy is variable,” Zeeshan Haq, MD, a retina specialist at Retinal Consultants of Minnesota, told this news organization. Dr. Hag presented the findings Nov. 3 at the annual meeting of the American Academy of Ophthalmology.
“Based on this preliminary evidence and what we know so far, it suggests that there is a risk of worsening, but it’s quite low for most patients, and so a conversation needs to be had between anyone considering prescribing the drug, such as a general practitioner or a nurse practitioner, and that patient’s optometrist or comprehensive ophthalmologist or retina specialist.”
Methodology and results
Dr. Haq reported on a retrospective case series of 96,462 eyes from the Intelligent Research in Sight (IRIS) registry. Patients had type 2 diabetes and began taking injectable semaglutide between January 2013 and December 2021.
The study evaluated eyes with three levels of retinopathy:
- No retinopathy or background retinopathy (71.8%).
- Mild or moderate nonproliferative diabetic retinopathy (NPDR) (18.4%).
- Severe NPDR or proliferative diabetic retinopathy (PDR) (9.8%).
In eyes with no or background retinopathy, 1.3%, 1.2%, 1.6%, and 2.2% experienced a worsening in status of the condition at 3, 6, 12, and 24 months, respectively.
In eyes with mild or moderate NPDR, 2.4%, 3%, 3.4%, and 3.5% showed worsening retinopathy at the respective time intervals.
Improvement of retinopathy rather than worsening was evaluated in the eyes with severe NPDR or PDR. At 3, 6, 12, and 24 months, improvement was observed in 40%, 37.8%, 47.7%, and 58.7% of these eyes, respectively.
Most patients were aged 51-75 years (77.2%), female (55.0%), and White (63.8%).
The study found low rates of the following complications across the same time intervals: vitreous hemorrhage (from 0.1% to 0.15%); traction retinal detachment (0.02% to 0.05%); and neovascular glaucoma (0.03% to –0.04%), Dr. Haq reported.
Dr. Haq noted that understanding the possible consequences that semaglutide has on vision is important as the drug becomes more widely available for both diabetes and weight control. The Centers for Disease Control and Prevention reports that 37.3 million people in the United States have diabetes; 28.7 million cases have been diagnosed, and 8.5 million are undiagnosed.
Clinical implications
“Any patient in the United States with diabetes has to undergo screening for diabetic eye disease, and so they’re usually plugged into the eye-care system,” Dr. Haq said. “But if they’re going to be starting this drug and they don’t have any existing diabetic retinopathy, the discussion should be had between their doctor and the eye-care provider, and if they do have a history of DR, an evaluation with the eye-care provider should probably happen upon starting the drug.”
Vaidehi Dedania, MD, a retina specialist at NYU Langone Health in New York, said the findings underscore the importance of counseling patients who are taking semaglutide about potential vision outcomes.
“We know that when patients get rapid control of their diabetes, their diabetic retinopathy can worsen in the short term, although it always ends up doing better in long term anyway,” Dr. Dedania said in an interview. “We always educate our patients that if they get control of the diabetes to not feel discouraged if their diabetic retinopathy worsens despite getting good control, because we know in the long run it always get better.”
The new findings, however, may have masked some worsening of retinopathy because of how the researchers categorized the condition. “It’s hard to assess changes within a designation because they’re so broad,” Dr. Dedania said.
She also noted potential limitations with the IRIS database itself. “The data collected from it are not always as complete as you might need for the purpose of understanding this, so that’s a limitation,” she said. While the high number of patients is a strength of the study, she added, “I still think the limitations are pretty significant.”
Dr. Haq has disclosed no relevant financial relationships. Dr. Dedania has relationships with Genentech/Roche and Regeneron Pharmaceuticals.
A version of this article first appeared on Medscape.com.
Trial shows utility of small-volume blood collection tubes
A large Canadian clinical trial has found that using small-volume tubes to collect blood samples for laboratory testing of intensive care unit patients can reduce blood transfusions without affecting lab results.
“We showed in a large pragmatic cluster trial that automatically collect less blood for laboratory testing reduced red blood cell transfusions by about 10 units of red blood cells per 100 patients in the ICU,” lead study author Deborah M. Siegal, MD, associate professor at the University of Ottawa and scientist at the Ottawa Hospital Research Institute, said.
The study was coordinated by the Population Health Research Institute, an affiliate of McMaster University in Hamilton (Ont.) Health Sciences, where Dr. Siegal worked before moving to Ottawa.
The STRATUS randomized clinical trial, published in JAMA, involved 25 adult medical-surgical ICUs across Canada, where 21,201 patients were randomized to either standard-volume or small-volume tubes for collecting blood samples. During the course of the study, each site switched to the small-volume collection tubes.
“We also showed there were no negative effects on lab testing, and by that we measured the sufficiency of the specimens,” Dr. Siegal added. “We were able to show that there wasn’t a problem with the amount of blood that was available for the tests to be done.”
The samples were collected from February 2019 through January 2021, through the period of COVID-19 restrictions. Dr. Siegal explained that 6,210 patients admitted early in the COVID-19 pandemic were excluded from the primary analysis, but were included in secondary analyses.
Study results
While the study found no significant difference in RBC units per patient per ICU stage – a relative risk of .91 (95% confidence interval, 0.79-1.05; P = .19), it did find an absolute reduction of 7.24 RBC units/100 patients per ICU stay.
Findings from the secondary analyses, which included 27,411 patients, were:
- A 12% reduction in RBC units per patient per ICU stay after switching from standard-volume to small-volume tubes (RR, 0.88; 95% CI, 0.77-1; P = .04).
- An absolute reduction of 9.84 RBC units/100 patients per ICU stay (95% CI, 0.24-20.76).
In the primary analysis population, the median transfusion-adjusted hemoglobin was not statistically different between the standard- and small-volume collection tube groups, with an average difference of 0.1 g/dL (95% CI, –0.04 to .23), but it was lower in the secondary population, with a mean difference of .17 g/dL (95% CI, 0.05-0.29).
“Those patients that we analyzed in the secondary analysis population received about 36,000 units of blood, just in 25 ICU units in Canada in less than 2 years,” Dr. Siegal said. “If we saved 10 units per 100 patients, that’s 1,500 units of blood. That really speaks to a small effect at the individual patient level but really potential for widespread effect. We are now in a period of blood product shortage not only in Canada but worldwide.”
First clinical trial for small tubes
Dr. Siegal noted this was the first clinical trial to compare standard- and small-volume blood collection tools, “and also to show there is both a benefit and a lack of harm,” Dr. Siegal said. “We thought that a randomized trial was the best way to move the needle. If we could design a trial of a large population of patients to show benefit and no harm, it would be a win, and that’s in fact what happened.”
She added, “The tubes essentially have the same cost, work the same, and go on the same equipment the same way the standard-volume tubes do, so it wasn’t a practice change for people in the hospital.”
The study also found an identical low rate of unusable specimens did not differ regardless of the type of collection tube: less than .03%.
Dr. Siegal said the study group is collaborating with hematology stakeholders in Canada, including Canadian Blood Services, which provides blood plasma to the country’s provincial and territorial health systems, and is reaching out to the American Society of Hematology.
“We’re going to target both hematologists and critical care providers and, even more broadly than the critical care community, hospitals, because anemia is big problem in hospitals,” Dr. Siegal said. “I think we can think about this more broadly.”
The study received funding from the Hamilton Academic Health Sciences Organization. Dr. Siegal disclosed relationships with Bristol-Myers Squibb-Pfizer, AstraZeneca and Roche.
A large Canadian clinical trial has found that using small-volume tubes to collect blood samples for laboratory testing of intensive care unit patients can reduce blood transfusions without affecting lab results.
“We showed in a large pragmatic cluster trial that automatically collect less blood for laboratory testing reduced red blood cell transfusions by about 10 units of red blood cells per 100 patients in the ICU,” lead study author Deborah M. Siegal, MD, associate professor at the University of Ottawa and scientist at the Ottawa Hospital Research Institute, said.
The study was coordinated by the Population Health Research Institute, an affiliate of McMaster University in Hamilton (Ont.) Health Sciences, where Dr. Siegal worked before moving to Ottawa.
The STRATUS randomized clinical trial, published in JAMA, involved 25 adult medical-surgical ICUs across Canada, where 21,201 patients were randomized to either standard-volume or small-volume tubes for collecting blood samples. During the course of the study, each site switched to the small-volume collection tubes.
“We also showed there were no negative effects on lab testing, and by that we measured the sufficiency of the specimens,” Dr. Siegal added. “We were able to show that there wasn’t a problem with the amount of blood that was available for the tests to be done.”
The samples were collected from February 2019 through January 2021, through the period of COVID-19 restrictions. Dr. Siegal explained that 6,210 patients admitted early in the COVID-19 pandemic were excluded from the primary analysis, but were included in secondary analyses.
Study results
While the study found no significant difference in RBC units per patient per ICU stage – a relative risk of .91 (95% confidence interval, 0.79-1.05; P = .19), it did find an absolute reduction of 7.24 RBC units/100 patients per ICU stay.
Findings from the secondary analyses, which included 27,411 patients, were:
- A 12% reduction in RBC units per patient per ICU stay after switching from standard-volume to small-volume tubes (RR, 0.88; 95% CI, 0.77-1; P = .04).
- An absolute reduction of 9.84 RBC units/100 patients per ICU stay (95% CI, 0.24-20.76).
In the primary analysis population, the median transfusion-adjusted hemoglobin was not statistically different between the standard- and small-volume collection tube groups, with an average difference of 0.1 g/dL (95% CI, –0.04 to .23), but it was lower in the secondary population, with a mean difference of .17 g/dL (95% CI, 0.05-0.29).
“Those patients that we analyzed in the secondary analysis population received about 36,000 units of blood, just in 25 ICU units in Canada in less than 2 years,” Dr. Siegal said. “If we saved 10 units per 100 patients, that’s 1,500 units of blood. That really speaks to a small effect at the individual patient level but really potential for widespread effect. We are now in a period of blood product shortage not only in Canada but worldwide.”
First clinical trial for small tubes
Dr. Siegal noted this was the first clinical trial to compare standard- and small-volume blood collection tools, “and also to show there is both a benefit and a lack of harm,” Dr. Siegal said. “We thought that a randomized trial was the best way to move the needle. If we could design a trial of a large population of patients to show benefit and no harm, it would be a win, and that’s in fact what happened.”
She added, “The tubes essentially have the same cost, work the same, and go on the same equipment the same way the standard-volume tubes do, so it wasn’t a practice change for people in the hospital.”
The study also found an identical low rate of unusable specimens did not differ regardless of the type of collection tube: less than .03%.
Dr. Siegal said the study group is collaborating with hematology stakeholders in Canada, including Canadian Blood Services, which provides blood plasma to the country’s provincial and territorial health systems, and is reaching out to the American Society of Hematology.
“We’re going to target both hematologists and critical care providers and, even more broadly than the critical care community, hospitals, because anemia is big problem in hospitals,” Dr. Siegal said. “I think we can think about this more broadly.”
The study received funding from the Hamilton Academic Health Sciences Organization. Dr. Siegal disclosed relationships with Bristol-Myers Squibb-Pfizer, AstraZeneca and Roche.
A large Canadian clinical trial has found that using small-volume tubes to collect blood samples for laboratory testing of intensive care unit patients can reduce blood transfusions without affecting lab results.
“We showed in a large pragmatic cluster trial that automatically collect less blood for laboratory testing reduced red blood cell transfusions by about 10 units of red blood cells per 100 patients in the ICU,” lead study author Deborah M. Siegal, MD, associate professor at the University of Ottawa and scientist at the Ottawa Hospital Research Institute, said.
The study was coordinated by the Population Health Research Institute, an affiliate of McMaster University in Hamilton (Ont.) Health Sciences, where Dr. Siegal worked before moving to Ottawa.
The STRATUS randomized clinical trial, published in JAMA, involved 25 adult medical-surgical ICUs across Canada, where 21,201 patients were randomized to either standard-volume or small-volume tubes for collecting blood samples. During the course of the study, each site switched to the small-volume collection tubes.
“We also showed there were no negative effects on lab testing, and by that we measured the sufficiency of the specimens,” Dr. Siegal added. “We were able to show that there wasn’t a problem with the amount of blood that was available for the tests to be done.”
The samples were collected from February 2019 through January 2021, through the period of COVID-19 restrictions. Dr. Siegal explained that 6,210 patients admitted early in the COVID-19 pandemic were excluded from the primary analysis, but were included in secondary analyses.
Study results
While the study found no significant difference in RBC units per patient per ICU stage – a relative risk of .91 (95% confidence interval, 0.79-1.05; P = .19), it did find an absolute reduction of 7.24 RBC units/100 patients per ICU stay.
Findings from the secondary analyses, which included 27,411 patients, were:
- A 12% reduction in RBC units per patient per ICU stay after switching from standard-volume to small-volume tubes (RR, 0.88; 95% CI, 0.77-1; P = .04).
- An absolute reduction of 9.84 RBC units/100 patients per ICU stay (95% CI, 0.24-20.76).
In the primary analysis population, the median transfusion-adjusted hemoglobin was not statistically different between the standard- and small-volume collection tube groups, with an average difference of 0.1 g/dL (95% CI, –0.04 to .23), but it was lower in the secondary population, with a mean difference of .17 g/dL (95% CI, 0.05-0.29).
“Those patients that we analyzed in the secondary analysis population received about 36,000 units of blood, just in 25 ICU units in Canada in less than 2 years,” Dr. Siegal said. “If we saved 10 units per 100 patients, that’s 1,500 units of blood. That really speaks to a small effect at the individual patient level but really potential for widespread effect. We are now in a period of blood product shortage not only in Canada but worldwide.”
First clinical trial for small tubes
Dr. Siegal noted this was the first clinical trial to compare standard- and small-volume blood collection tools, “and also to show there is both a benefit and a lack of harm,” Dr. Siegal said. “We thought that a randomized trial was the best way to move the needle. If we could design a trial of a large population of patients to show benefit and no harm, it would be a win, and that’s in fact what happened.”
She added, “The tubes essentially have the same cost, work the same, and go on the same equipment the same way the standard-volume tubes do, so it wasn’t a practice change for people in the hospital.”
The study also found an identical low rate of unusable specimens did not differ regardless of the type of collection tube: less than .03%.
Dr. Siegal said the study group is collaborating with hematology stakeholders in Canada, including Canadian Blood Services, which provides blood plasma to the country’s provincial and territorial health systems, and is reaching out to the American Society of Hematology.
“We’re going to target both hematologists and critical care providers and, even more broadly than the critical care community, hospitals, because anemia is big problem in hospitals,” Dr. Siegal said. “I think we can think about this more broadly.”
The study received funding from the Hamilton Academic Health Sciences Organization. Dr. Siegal disclosed relationships with Bristol-Myers Squibb-Pfizer, AstraZeneca and Roche.
FROM JAMA
Dropping aspirin cuts bleeding in LVAD patients: ARIES-HM3
PHILADELPHIA – particularly if it’s a newer device that does not use the centrifugal- or continuous-flow pump technology of conventional LVADs, new randomized results suggest.
“We’ve always thought that somehow aspirin prevents stroke and prevents clotting and that it’s anti-inflammatory, and what we found in ARIES was the exact opposite,” said Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, both in Boston, who reported results of the ARIES-HM3 trial of the HeartMate 3 LVAD, a device that uses a fully magnetically levitated rotor to maintain blood flow.
ARIES-HM3 randomly assigned 589 patients who received the HeartMate 3 device to vitamin K therapy with aspirin or to placebo. Dr. Mehra said it was the first international trial to conclusively evaluate medical therapy in patients who get an LVAD.
Unexpected findings
“To be honest with you, we set this up as a safety study to see if we could eliminate aspirin,” Dr. Mehra said in an interview. “We didn’t expect that the bleeding rates would decrease by 34% and that gastrointestinal bleeding in particular would decrease by 40%. We didn’t expect that it would nearly halve the days spent in the hospital, and we didn’t expect that the cost of care would decrease by 40%.”
Dr. Mehra reported the results at the annual scientific sessions of the American Heart Association. They were published simultaneously online in JAMA.
The researchers found that 74% of patients in the placebo group met the primary endpoint of being alive and not having any hemocompatibility events at 12 months vs 68% of the aspirin patients. The rate of nonsurgical bleeding events was 30% in the placebo group versus 42.4% in the aspirin patients. The rates of GI bleeding were 13% and 21.6% in the respective groups.
In his talk, Dr. Mehra noted the placebo group spent 47% fewer days in the hospital for bleeding, with hospitalization costs 41% lower than the aspirin group.
“We are very quick to throw things as deemed medical therapy at patients and this study outcome should give us pause that not everything we do may be right, and that we need to start building a stronger evidence base in medical therapy for what we do with patients that are on device support,” Dr. Mehra said.
Shift of focus to therapy
The study’s focus on aspirin therapy may be as significant as its evaluation of the HeartMate 3 LVAD, discussant Eric David Adler, MD, a cardiologist and section head of heart transplant at the University of California, San Diego, said in an interview.
“We focus so much on the device,” he said. “It’s like a set-it-and-forget-it kind of thing and we’re surprised that we see complications because we haven’t put a lot of effort into the medical therapy component.”
But he credited this study for doing just that, adding that it can serve as a model for future studies of LVADs, although such studies can face hurdles. “These studies are not trivial to accomplish,” he said. “Placebo medical therapy studies are very expensive, but I think this is a mandate for doing more studies. This is just the tip of the iceberg.”
Additionally, evaluating hospital stays in LVAD studies “is a really important endpoint,” Dr. Adler said.
“For me, one of the key things that we don’t think about enough is that lowering days in the hospital is a really big deal,” he said. “No one wants to spend time in the hospital, so anything we can do to lower the amount of hospital days is real impactful.”
Abbott funded and sponsored the ARIES-HM3 trial. Dr. Mehra disclosed relationships with Abbott, Moderna, Natera, Transmedics, Paragonix, NupulseCV, FineHeart, and Leviticus. Dr. Adler has disclosed no relevant financial relationships.
PHILADELPHIA – particularly if it’s a newer device that does not use the centrifugal- or continuous-flow pump technology of conventional LVADs, new randomized results suggest.
“We’ve always thought that somehow aspirin prevents stroke and prevents clotting and that it’s anti-inflammatory, and what we found in ARIES was the exact opposite,” said Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, both in Boston, who reported results of the ARIES-HM3 trial of the HeartMate 3 LVAD, a device that uses a fully magnetically levitated rotor to maintain blood flow.
ARIES-HM3 randomly assigned 589 patients who received the HeartMate 3 device to vitamin K therapy with aspirin or to placebo. Dr. Mehra said it was the first international trial to conclusively evaluate medical therapy in patients who get an LVAD.
Unexpected findings
“To be honest with you, we set this up as a safety study to see if we could eliminate aspirin,” Dr. Mehra said in an interview. “We didn’t expect that the bleeding rates would decrease by 34% and that gastrointestinal bleeding in particular would decrease by 40%. We didn’t expect that it would nearly halve the days spent in the hospital, and we didn’t expect that the cost of care would decrease by 40%.”
Dr. Mehra reported the results at the annual scientific sessions of the American Heart Association. They were published simultaneously online in JAMA.
The researchers found that 74% of patients in the placebo group met the primary endpoint of being alive and not having any hemocompatibility events at 12 months vs 68% of the aspirin patients. The rate of nonsurgical bleeding events was 30% in the placebo group versus 42.4% in the aspirin patients. The rates of GI bleeding were 13% and 21.6% in the respective groups.
In his talk, Dr. Mehra noted the placebo group spent 47% fewer days in the hospital for bleeding, with hospitalization costs 41% lower than the aspirin group.
“We are very quick to throw things as deemed medical therapy at patients and this study outcome should give us pause that not everything we do may be right, and that we need to start building a stronger evidence base in medical therapy for what we do with patients that are on device support,” Dr. Mehra said.
Shift of focus to therapy
The study’s focus on aspirin therapy may be as significant as its evaluation of the HeartMate 3 LVAD, discussant Eric David Adler, MD, a cardiologist and section head of heart transplant at the University of California, San Diego, said in an interview.
“We focus so much on the device,” he said. “It’s like a set-it-and-forget-it kind of thing and we’re surprised that we see complications because we haven’t put a lot of effort into the medical therapy component.”
But he credited this study for doing just that, adding that it can serve as a model for future studies of LVADs, although such studies can face hurdles. “These studies are not trivial to accomplish,” he said. “Placebo medical therapy studies are very expensive, but I think this is a mandate for doing more studies. This is just the tip of the iceberg.”
Additionally, evaluating hospital stays in LVAD studies “is a really important endpoint,” Dr. Adler said.
“For me, one of the key things that we don’t think about enough is that lowering days in the hospital is a really big deal,” he said. “No one wants to spend time in the hospital, so anything we can do to lower the amount of hospital days is real impactful.”
Abbott funded and sponsored the ARIES-HM3 trial. Dr. Mehra disclosed relationships with Abbott, Moderna, Natera, Transmedics, Paragonix, NupulseCV, FineHeart, and Leviticus. Dr. Adler has disclosed no relevant financial relationships.
PHILADELPHIA – particularly if it’s a newer device that does not use the centrifugal- or continuous-flow pump technology of conventional LVADs, new randomized results suggest.
“We’ve always thought that somehow aspirin prevents stroke and prevents clotting and that it’s anti-inflammatory, and what we found in ARIES was the exact opposite,” said Mandeep Mehra, MD, of Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, both in Boston, who reported results of the ARIES-HM3 trial of the HeartMate 3 LVAD, a device that uses a fully magnetically levitated rotor to maintain blood flow.
ARIES-HM3 randomly assigned 589 patients who received the HeartMate 3 device to vitamin K therapy with aspirin or to placebo. Dr. Mehra said it was the first international trial to conclusively evaluate medical therapy in patients who get an LVAD.
Unexpected findings
“To be honest with you, we set this up as a safety study to see if we could eliminate aspirin,” Dr. Mehra said in an interview. “We didn’t expect that the bleeding rates would decrease by 34% and that gastrointestinal bleeding in particular would decrease by 40%. We didn’t expect that it would nearly halve the days spent in the hospital, and we didn’t expect that the cost of care would decrease by 40%.”
Dr. Mehra reported the results at the annual scientific sessions of the American Heart Association. They were published simultaneously online in JAMA.
The researchers found that 74% of patients in the placebo group met the primary endpoint of being alive and not having any hemocompatibility events at 12 months vs 68% of the aspirin patients. The rate of nonsurgical bleeding events was 30% in the placebo group versus 42.4% in the aspirin patients. The rates of GI bleeding were 13% and 21.6% in the respective groups.
In his talk, Dr. Mehra noted the placebo group spent 47% fewer days in the hospital for bleeding, with hospitalization costs 41% lower than the aspirin group.
“We are very quick to throw things as deemed medical therapy at patients and this study outcome should give us pause that not everything we do may be right, and that we need to start building a stronger evidence base in medical therapy for what we do with patients that are on device support,” Dr. Mehra said.
Shift of focus to therapy
The study’s focus on aspirin therapy may be as significant as its evaluation of the HeartMate 3 LVAD, discussant Eric David Adler, MD, a cardiologist and section head of heart transplant at the University of California, San Diego, said in an interview.
“We focus so much on the device,” he said. “It’s like a set-it-and-forget-it kind of thing and we’re surprised that we see complications because we haven’t put a lot of effort into the medical therapy component.”
But he credited this study for doing just that, adding that it can serve as a model for future studies of LVADs, although such studies can face hurdles. “These studies are not trivial to accomplish,” he said. “Placebo medical therapy studies are very expensive, but I think this is a mandate for doing more studies. This is just the tip of the iceberg.”
Additionally, evaluating hospital stays in LVAD studies “is a really important endpoint,” Dr. Adler said.
“For me, one of the key things that we don’t think about enough is that lowering days in the hospital is a really big deal,” he said. “No one wants to spend time in the hospital, so anything we can do to lower the amount of hospital days is real impactful.”
Abbott funded and sponsored the ARIES-HM3 trial. Dr. Mehra disclosed relationships with Abbott, Moderna, Natera, Transmedics, Paragonix, NupulseCV, FineHeart, and Leviticus. Dr. Adler has disclosed no relevant financial relationships.
AT AHA 2023