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Decoding AFib recurrence: PCPs’ role in personalized care
One in three patients who experience their first bout of atrial fibrillation (AFib) during hospitalization can expect to experience a recurrence of the arrhythmia within the year, new research shows.
The findings, reported in Annals of Internal Medicine, suggest these patients may be good candidates for oral anticoagulants to reduce their risk for stroke.
“Atrial fibrillation is very common in patients for the very first time in their life when they’re sick and in the hospital,” said William F. McIntyre, MD, PhD, a cardiologist at McMaster University, Hamilton, Ont., who led the study. These new insights into AFib management suggest there is a need for primary care physicians to be on the lookout for potential recurrence.
AFib is strongly linked to stroke, and patients at greater risk for stroke may be prescribed oral anticoagulants. Although the arrhythmia can be reversed before the patient is discharged from the hospital, risk for recurrence was unclear, Dr. McIntyre said.
“We wanted to know if the patient was in atrial fibrillation because of the physiologic stress that they were under, or if they just have the disease called atrial fibrillation, which should usually be followed lifelong by a specialist,” Dr. McIntyre said.
Dr. McIntyre and colleagues followed 139 patients (mean age, 71 years) at three medical centers in Ontario who experienced new-onset AFib during their hospital stay, along with an equal number of patients who had no history of AFib and who served as controls. The research team used a Holter monitor to record study participants’ heart rhythm for 14 days to detect incident AFib at 1 and 6 months after discharge. They also followed up with periodic phone calls for up to 12 months. Among the study participants, half were admitted for noncardiac surgeries, and the other half were admitted for medical illnesses, including infections and pneumonia. Participants with a prior history of AFib were excluded from the analysis.
The primary outcome of the study was an episode of AFib that lasted at least 30 seconds on the monitor or one detected during routine care at the 12-month mark.
Patients who experienced AFib for the first time in the hospital had roughly a 33% risk for recurrence within a year, nearly sevenfold higher than their age- and sex-matched counterparts who had not had an arrhythmia during their hospital stay (3%; confidence interval, 0%-6.4%).
“This study has important implications for management of patients who have a first presentation of AFib that is concurrent with a reversible physiologic stressor,” the authors wrote. “An AFib recurrence risk of 33.1% at 1 year is neither low enough to conclude that transient new-onset AFib in the setting of another illness is benign nor high enough that all such transient new-onset AFib can be assumed to be paroxysmal AFib. Instead, these results call for risk stratification and follow-up in these patients.”
The researchers reported that among people with recurrent AFib in the study, the median total time in arrhythmia was 9 hours. “This far exceeds the cutoff of 6 minutes that was established as being associated with stroke using simulated AFib screening in patients with implanted continuous monitors,” they wrote. “These results suggest that the patients in our study who had AFib detected in follow-up are similar to contemporary patients with AFib for whom evidence-based therapies, including oral anticoagulation, are warranted.”
Dr. McIntyre and colleagues were able to track outcomes and treatments for the patients in the study. In the group with recurrent AFib, 1 had a stroke, 2 experienced systemic embolism, 3 had a heart failure event, 6 experienced bleeding, and 11 died. In the other group, there was one case of stroke, one of heart failure, four cases involving bleeding, and seven deaths. “The proportion of participants with new-onset AFib during their initial hospitalization who were taking oral anticoagulants was 47.1% at 6 months and 49.2% at 12 months. This included 73% of participants with AFib detected during follow-up and 39% who did not have AFib detected during follow-up,” they wrote.
The uncertain nature of AFib recurrence complicates predictions about patients’ posthospitalization experiences within the following year. “We cannot just say: ‘Hey, this is just a reversible illness, and now we can forget about it,’ ” Dr. McIntyre said. “Nor is the risk of recurrence so strong in the other direction that you can give patients a lifelong diagnosis of atrial fibrillation.”
Role for primary care
Without that certainty, physicians cannot refer everyone who experiences new-onset AFib to a cardiologist for long-term care. The variability in recurrence rates necessitates a more nuanced and personalized approach. Here, primary care physicians step in, offering tailored care based on their established, long-term patient relationships, Dr. McIntyre said.
The study participants already have chronic health conditions that bring them into regular contact with their family physician. This gives primary care physicians a golden opportunity to be on lookout and to recommend care from a cardiologist at the appropriate time if it becomes necessary, he said.
“I have certainly seen cases of recurrent atrial fibrillation in patients who had an episode while hospitalized, and consistent with this study, this is a common clinical occurrence,” said Deepak L. Bhatt, MD, MPH, director of Mount Sinai Heart, New York. Primary care physicians must remain vigilant and avoid the temptation to attribute AFib solely to illness or surgery
“Ideally, we would have randomized clinical trial data to guide the decision about whether to use prophylactic anticoagulation,” said Dr. Bhatt, who added that a cardiology consultation may also be appropriate.
Dr. McIntyre reported no relevant financial relationships. Dr. Bhatt reported numerous relationships with industry.
A version of this article appeared on Medscape.com.
One in three patients who experience their first bout of atrial fibrillation (AFib) during hospitalization can expect to experience a recurrence of the arrhythmia within the year, new research shows.
The findings, reported in Annals of Internal Medicine, suggest these patients may be good candidates for oral anticoagulants to reduce their risk for stroke.
“Atrial fibrillation is very common in patients for the very first time in their life when they’re sick and in the hospital,” said William F. McIntyre, MD, PhD, a cardiologist at McMaster University, Hamilton, Ont., who led the study. These new insights into AFib management suggest there is a need for primary care physicians to be on the lookout for potential recurrence.
AFib is strongly linked to stroke, and patients at greater risk for stroke may be prescribed oral anticoagulants. Although the arrhythmia can be reversed before the patient is discharged from the hospital, risk for recurrence was unclear, Dr. McIntyre said.
“We wanted to know if the patient was in atrial fibrillation because of the physiologic stress that they were under, or if they just have the disease called atrial fibrillation, which should usually be followed lifelong by a specialist,” Dr. McIntyre said.
Dr. McIntyre and colleagues followed 139 patients (mean age, 71 years) at three medical centers in Ontario who experienced new-onset AFib during their hospital stay, along with an equal number of patients who had no history of AFib and who served as controls. The research team used a Holter monitor to record study participants’ heart rhythm for 14 days to detect incident AFib at 1 and 6 months after discharge. They also followed up with periodic phone calls for up to 12 months. Among the study participants, half were admitted for noncardiac surgeries, and the other half were admitted for medical illnesses, including infections and pneumonia. Participants with a prior history of AFib were excluded from the analysis.
The primary outcome of the study was an episode of AFib that lasted at least 30 seconds on the monitor or one detected during routine care at the 12-month mark.
Patients who experienced AFib for the first time in the hospital had roughly a 33% risk for recurrence within a year, nearly sevenfold higher than their age- and sex-matched counterparts who had not had an arrhythmia during their hospital stay (3%; confidence interval, 0%-6.4%).
“This study has important implications for management of patients who have a first presentation of AFib that is concurrent with a reversible physiologic stressor,” the authors wrote. “An AFib recurrence risk of 33.1% at 1 year is neither low enough to conclude that transient new-onset AFib in the setting of another illness is benign nor high enough that all such transient new-onset AFib can be assumed to be paroxysmal AFib. Instead, these results call for risk stratification and follow-up in these patients.”
The researchers reported that among people with recurrent AFib in the study, the median total time in arrhythmia was 9 hours. “This far exceeds the cutoff of 6 minutes that was established as being associated with stroke using simulated AFib screening in patients with implanted continuous monitors,” they wrote. “These results suggest that the patients in our study who had AFib detected in follow-up are similar to contemporary patients with AFib for whom evidence-based therapies, including oral anticoagulation, are warranted.”
Dr. McIntyre and colleagues were able to track outcomes and treatments for the patients in the study. In the group with recurrent AFib, 1 had a stroke, 2 experienced systemic embolism, 3 had a heart failure event, 6 experienced bleeding, and 11 died. In the other group, there was one case of stroke, one of heart failure, four cases involving bleeding, and seven deaths. “The proportion of participants with new-onset AFib during their initial hospitalization who were taking oral anticoagulants was 47.1% at 6 months and 49.2% at 12 months. This included 73% of participants with AFib detected during follow-up and 39% who did not have AFib detected during follow-up,” they wrote.
The uncertain nature of AFib recurrence complicates predictions about patients’ posthospitalization experiences within the following year. “We cannot just say: ‘Hey, this is just a reversible illness, and now we can forget about it,’ ” Dr. McIntyre said. “Nor is the risk of recurrence so strong in the other direction that you can give patients a lifelong diagnosis of atrial fibrillation.”
Role for primary care
Without that certainty, physicians cannot refer everyone who experiences new-onset AFib to a cardiologist for long-term care. The variability in recurrence rates necessitates a more nuanced and personalized approach. Here, primary care physicians step in, offering tailored care based on their established, long-term patient relationships, Dr. McIntyre said.
The study participants already have chronic health conditions that bring them into regular contact with their family physician. This gives primary care physicians a golden opportunity to be on lookout and to recommend care from a cardiologist at the appropriate time if it becomes necessary, he said.
“I have certainly seen cases of recurrent atrial fibrillation in patients who had an episode while hospitalized, and consistent with this study, this is a common clinical occurrence,” said Deepak L. Bhatt, MD, MPH, director of Mount Sinai Heart, New York. Primary care physicians must remain vigilant and avoid the temptation to attribute AFib solely to illness or surgery
“Ideally, we would have randomized clinical trial data to guide the decision about whether to use prophylactic anticoagulation,” said Dr. Bhatt, who added that a cardiology consultation may also be appropriate.
Dr. McIntyre reported no relevant financial relationships. Dr. Bhatt reported numerous relationships with industry.
A version of this article appeared on Medscape.com.
One in three patients who experience their first bout of atrial fibrillation (AFib) during hospitalization can expect to experience a recurrence of the arrhythmia within the year, new research shows.
The findings, reported in Annals of Internal Medicine, suggest these patients may be good candidates for oral anticoagulants to reduce their risk for stroke.
“Atrial fibrillation is very common in patients for the very first time in their life when they’re sick and in the hospital,” said William F. McIntyre, MD, PhD, a cardiologist at McMaster University, Hamilton, Ont., who led the study. These new insights into AFib management suggest there is a need for primary care physicians to be on the lookout for potential recurrence.
AFib is strongly linked to stroke, and patients at greater risk for stroke may be prescribed oral anticoagulants. Although the arrhythmia can be reversed before the patient is discharged from the hospital, risk for recurrence was unclear, Dr. McIntyre said.
“We wanted to know if the patient was in atrial fibrillation because of the physiologic stress that they were under, or if they just have the disease called atrial fibrillation, which should usually be followed lifelong by a specialist,” Dr. McIntyre said.
Dr. McIntyre and colleagues followed 139 patients (mean age, 71 years) at three medical centers in Ontario who experienced new-onset AFib during their hospital stay, along with an equal number of patients who had no history of AFib and who served as controls. The research team used a Holter monitor to record study participants’ heart rhythm for 14 days to detect incident AFib at 1 and 6 months after discharge. They also followed up with periodic phone calls for up to 12 months. Among the study participants, half were admitted for noncardiac surgeries, and the other half were admitted for medical illnesses, including infections and pneumonia. Participants with a prior history of AFib were excluded from the analysis.
The primary outcome of the study was an episode of AFib that lasted at least 30 seconds on the monitor or one detected during routine care at the 12-month mark.
Patients who experienced AFib for the first time in the hospital had roughly a 33% risk for recurrence within a year, nearly sevenfold higher than their age- and sex-matched counterparts who had not had an arrhythmia during their hospital stay (3%; confidence interval, 0%-6.4%).
“This study has important implications for management of patients who have a first presentation of AFib that is concurrent with a reversible physiologic stressor,” the authors wrote. “An AFib recurrence risk of 33.1% at 1 year is neither low enough to conclude that transient new-onset AFib in the setting of another illness is benign nor high enough that all such transient new-onset AFib can be assumed to be paroxysmal AFib. Instead, these results call for risk stratification and follow-up in these patients.”
The researchers reported that among people with recurrent AFib in the study, the median total time in arrhythmia was 9 hours. “This far exceeds the cutoff of 6 minutes that was established as being associated with stroke using simulated AFib screening in patients with implanted continuous monitors,” they wrote. “These results suggest that the patients in our study who had AFib detected in follow-up are similar to contemporary patients with AFib for whom evidence-based therapies, including oral anticoagulation, are warranted.”
Dr. McIntyre and colleagues were able to track outcomes and treatments for the patients in the study. In the group with recurrent AFib, 1 had a stroke, 2 experienced systemic embolism, 3 had a heart failure event, 6 experienced bleeding, and 11 died. In the other group, there was one case of stroke, one of heart failure, four cases involving bleeding, and seven deaths. “The proportion of participants with new-onset AFib during their initial hospitalization who were taking oral anticoagulants was 47.1% at 6 months and 49.2% at 12 months. This included 73% of participants with AFib detected during follow-up and 39% who did not have AFib detected during follow-up,” they wrote.
The uncertain nature of AFib recurrence complicates predictions about patients’ posthospitalization experiences within the following year. “We cannot just say: ‘Hey, this is just a reversible illness, and now we can forget about it,’ ” Dr. McIntyre said. “Nor is the risk of recurrence so strong in the other direction that you can give patients a lifelong diagnosis of atrial fibrillation.”
Role for primary care
Without that certainty, physicians cannot refer everyone who experiences new-onset AFib to a cardiologist for long-term care. The variability in recurrence rates necessitates a more nuanced and personalized approach. Here, primary care physicians step in, offering tailored care based on their established, long-term patient relationships, Dr. McIntyre said.
The study participants already have chronic health conditions that bring them into regular contact with their family physician. This gives primary care physicians a golden opportunity to be on lookout and to recommend care from a cardiologist at the appropriate time if it becomes necessary, he said.
“I have certainly seen cases of recurrent atrial fibrillation in patients who had an episode while hospitalized, and consistent with this study, this is a common clinical occurrence,” said Deepak L. Bhatt, MD, MPH, director of Mount Sinai Heart, New York. Primary care physicians must remain vigilant and avoid the temptation to attribute AFib solely to illness or surgery
“Ideally, we would have randomized clinical trial data to guide the decision about whether to use prophylactic anticoagulation,” said Dr. Bhatt, who added that a cardiology consultation may also be appropriate.
Dr. McIntyre reported no relevant financial relationships. Dr. Bhatt reported numerous relationships with industry.
A version of this article appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Federal Health Care Data Trends 2023
Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner, highlighting the latest research and study outcomes related to the health of veteran and active-duty populations.
In this issue:
- Limb Loss and Prostheses
- Neurology
- Cardiology
- Mental Health
- Diabetes
- Rheumatoid Arthritis
- Respiratory illnesses
- Women's Health
- HPV and Related Cancers
Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner, highlighting the latest research and study outcomes related to the health of veteran and active-duty populations.
In this issue:
- Limb Loss and Prostheses
- Neurology
- Cardiology
- Mental Health
- Diabetes
- Rheumatoid Arthritis
- Respiratory illnesses
- Women's Health
- HPV and Related Cancers
Federal Health Care Data Trends (click to view the digital edition) is a special supplement to Federal Practitioner, highlighting the latest research and study outcomes related to the health of veteran and active-duty populations.
In this issue:
- Limb Loss and Prostheses
- Neurology
- Cardiology
- Mental Health
- Diabetes
- Rheumatoid Arthritis
- Respiratory illnesses
- Women's Health
- HPV and Related Cancers
PET scan at diagnosis may help to predict aneurysm risk in patients with giant cell arteritis
PET scans may serve as both a diagnostic and prognostic tool in giant cell arteritis (GCA), according to a new study.
In over 100 patients with GCA who underwent 18F-fluorodeoxyglucose PET imaging, those with elevated FDG uptake at diagnosis were more likely to develop thoracic aortic aneurysms.
“PET-CT has an excellent diagnostic accuracy for the diagnosis of GCA, certainly if both extracranial and intracranial vessels were assessed. This study shows that performing PET imaging at diagnosis in patients with GCA may also help estimate the future risk for aortic aneurysm formation,” lead author Lien Moreel, MD, of the department of internal medicine at University Hospitals Leuven (Belgium), wrote in an email. “PET imaging at diagnosis can provide both diagnostic and prognostic information in one imaging tool in patients with GCA.”
Previous retrospective studies have found an association between FDG uptake at diagnosis and risk for aortic complications, but “prospective studies confirming these findings are lacking,” the investigators wrote. The study was published online in Annals of Internal Medicine.
In the study, Dr. Moreel and colleagues prospectively followed 106 individuals diagnosed with GCA who received FDG-PET within 3 days after starting glucocorticoids. Patients also had CT imaging at diagnosis and then CT imaging annually for up to 10 years.
A PET scan was considered positive with an FDG uptake of grade 2 or higher in any of seven vascular regions (thoracic and abdominal aorta, subclavian, axillary, carotid, iliac, and femoral arteries). Researchers also used the results to quantify a total vascular score (TVS). Out of the entire cohort, 75 patients had a positive PET scan result.
These patients had a larger increase in the diameter of the ascending aorta and the descending aorta, as well the volume of thoracic aorta after 5 years, compared with those who had a negative PET scan result. These changes were also associated with higher TVS at diagnosis. Of the 23 patients who developed an aortic aneurysm, 18 had a positive PET scan at diagnosis.
The risk of incident thoracic aortic aneurysms was calculated to be 10 times higher in patients with positive PET scans. Fourteen of the 15 patients (93%) with an incident thoracic aortic aneurysm had positive PET results.
Up to now, “we’ve had no way of predicting which patients might be at risk of this potentially serious complication,” Kenneth Warrington, MD, chair of the department of rheumatology and director of the Vasculitis Clinic at the Mayo Clinic in Rochester, Minn., said in an interview. He was not involved with the research.
He hopes that the findings will help inform clinicians on how patients with GCA should be evaluated and monitored. Although the American College of Rheumatology conditionally recommends noninvasive imaging in patients newly diagnosed with GCA, guidance for follow-up on these patients is less clear.
“There are no clear guidelines, but most clinicians who take care of patients with GCA do obtain imaging periodically,” he said. “There is a lot of variability in the practice in terms of which type of scan is used and how often it’s done.”
Although this study did not specifically look at the benefit of screening patients, “we think that follow-up of aortic dimensions seems to be warranted in GCA patients with a positive PET scan result, especially in those with high intensity and broad extent of vascular inflammation,” Dr. Moreel said. “However, the added value of screening and the interval required should be addressed in future studies.”
Applying this study’s protocol in practice in the United States might be difficult, Dr. Warrington noted, as it can be challenging logistically to get imaging done within 3 days of starting steroids. However, Dr. Moreel said it is possible to delay the start of glucocorticoids until the PET scan is performed in patients without visual symptoms or jaw claudication.
PET scans are also expensive, and it can be difficult to get insurance coverage in the United States. However, other imaging modalities could potentially be used in similar ways, Dr. Warrington said. “One could potentially extrapolate to say that if there is difficulty with accessing PET scan, we could use other modalities like CT or MRI basically to see whether the aorta is inflamed or not.”
Dr. Moreel disclosed no relevant financial relationships. Dr. Warrington has received compensation for consulting activities with Sanofi. Eli Lilly, Kiniksa, and Bristol-Myers Squibb have provided support to the Mayo Clinic for clinical trials related to GCA, of which Dr. Warrington served as subinvestigator.
A version of this article appeared on Medscape.com.
PET scans may serve as both a diagnostic and prognostic tool in giant cell arteritis (GCA), according to a new study.
In over 100 patients with GCA who underwent 18F-fluorodeoxyglucose PET imaging, those with elevated FDG uptake at diagnosis were more likely to develop thoracic aortic aneurysms.
“PET-CT has an excellent diagnostic accuracy for the diagnosis of GCA, certainly if both extracranial and intracranial vessels were assessed. This study shows that performing PET imaging at diagnosis in patients with GCA may also help estimate the future risk for aortic aneurysm formation,” lead author Lien Moreel, MD, of the department of internal medicine at University Hospitals Leuven (Belgium), wrote in an email. “PET imaging at diagnosis can provide both diagnostic and prognostic information in one imaging tool in patients with GCA.”
Previous retrospective studies have found an association between FDG uptake at diagnosis and risk for aortic complications, but “prospective studies confirming these findings are lacking,” the investigators wrote. The study was published online in Annals of Internal Medicine.
In the study, Dr. Moreel and colleagues prospectively followed 106 individuals diagnosed with GCA who received FDG-PET within 3 days after starting glucocorticoids. Patients also had CT imaging at diagnosis and then CT imaging annually for up to 10 years.
A PET scan was considered positive with an FDG uptake of grade 2 or higher in any of seven vascular regions (thoracic and abdominal aorta, subclavian, axillary, carotid, iliac, and femoral arteries). Researchers also used the results to quantify a total vascular score (TVS). Out of the entire cohort, 75 patients had a positive PET scan result.
These patients had a larger increase in the diameter of the ascending aorta and the descending aorta, as well the volume of thoracic aorta after 5 years, compared with those who had a negative PET scan result. These changes were also associated with higher TVS at diagnosis. Of the 23 patients who developed an aortic aneurysm, 18 had a positive PET scan at diagnosis.
The risk of incident thoracic aortic aneurysms was calculated to be 10 times higher in patients with positive PET scans. Fourteen of the 15 patients (93%) with an incident thoracic aortic aneurysm had positive PET results.
Up to now, “we’ve had no way of predicting which patients might be at risk of this potentially serious complication,” Kenneth Warrington, MD, chair of the department of rheumatology and director of the Vasculitis Clinic at the Mayo Clinic in Rochester, Minn., said in an interview. He was not involved with the research.
He hopes that the findings will help inform clinicians on how patients with GCA should be evaluated and monitored. Although the American College of Rheumatology conditionally recommends noninvasive imaging in patients newly diagnosed with GCA, guidance for follow-up on these patients is less clear.
“There are no clear guidelines, but most clinicians who take care of patients with GCA do obtain imaging periodically,” he said. “There is a lot of variability in the practice in terms of which type of scan is used and how often it’s done.”
Although this study did not specifically look at the benefit of screening patients, “we think that follow-up of aortic dimensions seems to be warranted in GCA patients with a positive PET scan result, especially in those with high intensity and broad extent of vascular inflammation,” Dr. Moreel said. “However, the added value of screening and the interval required should be addressed in future studies.”
Applying this study’s protocol in practice in the United States might be difficult, Dr. Warrington noted, as it can be challenging logistically to get imaging done within 3 days of starting steroids. However, Dr. Moreel said it is possible to delay the start of glucocorticoids until the PET scan is performed in patients without visual symptoms or jaw claudication.
PET scans are also expensive, and it can be difficult to get insurance coverage in the United States. However, other imaging modalities could potentially be used in similar ways, Dr. Warrington said. “One could potentially extrapolate to say that if there is difficulty with accessing PET scan, we could use other modalities like CT or MRI basically to see whether the aorta is inflamed or not.”
Dr. Moreel disclosed no relevant financial relationships. Dr. Warrington has received compensation for consulting activities with Sanofi. Eli Lilly, Kiniksa, and Bristol-Myers Squibb have provided support to the Mayo Clinic for clinical trials related to GCA, of which Dr. Warrington served as subinvestigator.
A version of this article appeared on Medscape.com.
PET scans may serve as both a diagnostic and prognostic tool in giant cell arteritis (GCA), according to a new study.
In over 100 patients with GCA who underwent 18F-fluorodeoxyglucose PET imaging, those with elevated FDG uptake at diagnosis were more likely to develop thoracic aortic aneurysms.
“PET-CT has an excellent diagnostic accuracy for the diagnosis of GCA, certainly if both extracranial and intracranial vessels were assessed. This study shows that performing PET imaging at diagnosis in patients with GCA may also help estimate the future risk for aortic aneurysm formation,” lead author Lien Moreel, MD, of the department of internal medicine at University Hospitals Leuven (Belgium), wrote in an email. “PET imaging at diagnosis can provide both diagnostic and prognostic information in one imaging tool in patients with GCA.”
Previous retrospective studies have found an association between FDG uptake at diagnosis and risk for aortic complications, but “prospective studies confirming these findings are lacking,” the investigators wrote. The study was published online in Annals of Internal Medicine.
In the study, Dr. Moreel and colleagues prospectively followed 106 individuals diagnosed with GCA who received FDG-PET within 3 days after starting glucocorticoids. Patients also had CT imaging at diagnosis and then CT imaging annually for up to 10 years.
A PET scan was considered positive with an FDG uptake of grade 2 or higher in any of seven vascular regions (thoracic and abdominal aorta, subclavian, axillary, carotid, iliac, and femoral arteries). Researchers also used the results to quantify a total vascular score (TVS). Out of the entire cohort, 75 patients had a positive PET scan result.
These patients had a larger increase in the diameter of the ascending aorta and the descending aorta, as well the volume of thoracic aorta after 5 years, compared with those who had a negative PET scan result. These changes were also associated with higher TVS at diagnosis. Of the 23 patients who developed an aortic aneurysm, 18 had a positive PET scan at diagnosis.
The risk of incident thoracic aortic aneurysms was calculated to be 10 times higher in patients with positive PET scans. Fourteen of the 15 patients (93%) with an incident thoracic aortic aneurysm had positive PET results.
Up to now, “we’ve had no way of predicting which patients might be at risk of this potentially serious complication,” Kenneth Warrington, MD, chair of the department of rheumatology and director of the Vasculitis Clinic at the Mayo Clinic in Rochester, Minn., said in an interview. He was not involved with the research.
He hopes that the findings will help inform clinicians on how patients with GCA should be evaluated and monitored. Although the American College of Rheumatology conditionally recommends noninvasive imaging in patients newly diagnosed with GCA, guidance for follow-up on these patients is less clear.
“There are no clear guidelines, but most clinicians who take care of patients with GCA do obtain imaging periodically,” he said. “There is a lot of variability in the practice in terms of which type of scan is used and how often it’s done.”
Although this study did not specifically look at the benefit of screening patients, “we think that follow-up of aortic dimensions seems to be warranted in GCA patients with a positive PET scan result, especially in those with high intensity and broad extent of vascular inflammation,” Dr. Moreel said. “However, the added value of screening and the interval required should be addressed in future studies.”
Applying this study’s protocol in practice in the United States might be difficult, Dr. Warrington noted, as it can be challenging logistically to get imaging done within 3 days of starting steroids. However, Dr. Moreel said it is possible to delay the start of glucocorticoids until the PET scan is performed in patients without visual symptoms or jaw claudication.
PET scans are also expensive, and it can be difficult to get insurance coverage in the United States. However, other imaging modalities could potentially be used in similar ways, Dr. Warrington said. “One could potentially extrapolate to say that if there is difficulty with accessing PET scan, we could use other modalities like CT or MRI basically to see whether the aorta is inflamed or not.”
Dr. Moreel disclosed no relevant financial relationships. Dr. Warrington has received compensation for consulting activities with Sanofi. Eli Lilly, Kiniksa, and Bristol-Myers Squibb have provided support to the Mayo Clinic for clinical trials related to GCA, of which Dr. Warrington served as subinvestigator.
A version of this article appeared on Medscape.com.
FROM ANNALS OF INTERNAL MEDICINE
Multivitamins and dementia: Untangling the COSMOS study web
I have written before about the COSMOS study and its finding that multivitamins (and chocolate) did not improve brain or cardiovascular health. So I was surprised to read that a “new” study found that vitamins can forestall dementia and age-related cognitive decline.
Upon closer look, the new data are neither new nor convincing, at least to me.
Chocolate and multivitamins for CVD and cancer prevention
The large randomized COSMOS trial was supposed to be the definitive study on chocolate that would establish its heart-health benefits without a doubt. Or, rather, the benefits of a cocoa bean extract in pill form given to healthy, older volunteers. The COSMOS study was negative. Chocolate, or the cocoa bean extract they used, did not reduce cardiovascular events.
And yet for all the prepublication importance attached to COSMOS, it is scarcely mentioned. Had it been positive, rest assured that Mars, the candy bar company that cofunded the research, and other interested parties would have been shouting it from the rooftops. As it is, they’re already spinning it.
Which brings us to the multivitamin component. COSMOS actually had a 2 × 2 design. In other words, there were four groups in this study: chocolate plus multivitamin, chocolate plus placebo, placebo plus multivitamin, and placebo plus placebo. This type of study design allows you to study two different interventions simultaneously, provided that they are independent and do not interact with each other. In addition to the primary cardiovascular endpoint, they also studied a cancer endpoint.
The multivitamin supplement didn’t reduce cardiovascular events either. Nor did it affect cancer outcomes. The main COSMOS study was negative and reinforced what countless other studies have proven: Taking a daily multivitamin does not reduce your risk of having a heart attack or developing cancer.
But wait, there’s more: COSMOS-Mind
But no researcher worth his salt studies just one or two endpoints in a study. The participants also underwent neurologic and memory testing. These results were reported separately in the COSMOS-Mind study.
COSMOS-Mind is often described as a separate (or “new”) study. In reality, it included the same participants from the original COSMOS trial and measured yet another primary outcome of cognitive performance on a series of tests administered by telephone. Although there is nothing inherently wrong with studying multiple outcomes in your patient population (after all, that salami isn’t going to slice itself), they cannot all be primary outcomes. Some, by necessity, must be secondary hypothesis–generating outcomes. If you test enough endpoints, multiple hypothesis testing dictates that eventually you will get a positive result simply by chance.
There was a time when the neurocognitive outcomes of COSMOS would have been reported in the same paper as the cardiovascular outcomes, but that time seems to have passed us by. Researchers live or die by the number of their publications, and there is an inherent advantage to squeezing as many publications as possible from the same dataset. Though, to be fair, the journal would probably have asked them to split up the paper as well.
In brief, the cocoa extract again fell short in COSMOS-Mind, but the multivitamin arm did better on the composite cognitive outcome. It was a fairly small difference – a 0.07-point improvement on the z-score at the 3-year mark (the z-score is the mean divided by the standard deviation). Much was also made of the fact that the improvement seemed to vary by prior history of cardiovascular disease (CVD). Those with a history of CVD had a 0.11-point improvement, whereas those without had a 0.06-point improvement. The authors couldn’t offer a definitive explanation for these findings. Any argument that multivitamins improve cardiovascular health and therefore prevent vascular dementia has to contend with the fact that the main COSMOS study didn’t show a cardiovascular benefit for vitamins. Speculation that you are treating nutritional deficiencies is exactly that: speculation.
A more salient question is: What does a 0.07-point improvement on the z-score mean clinically? This study didn’t assess whether a multivitamin supplement prevented dementia or allowed people to live independently for longer. In fairness, that would have been exceptionally difficult to do and would have required a much longer study.
Their one attempt to quantify the cognitive benefit clinically was a calculation about normal age-related decline. Test scores were 0.045 points lower for every 1-year increase in age among participants (their mean age was 73 years). So the authors contend that a 0.07-point increase, or the 0.083-point increase that they found at year 3, corresponds to 1.8 years of age-related decline forestalled. Whether this is an appropriate assumption, I leave for the reader to decide.
COSMOS-Web and replication
The results of COSMOS-Mind were seemingly bolstered by the recent publication of COSMOS-Web. Although I’ve seen this study described as having replicated the results of COSMOS-Mind, that description is a bit misleading. This was yet another ancillary COSMOS study; more than half of the 2,262 participants in COSMOS-Mind were also included in COSMOS-Web. Replicating results in the same people isn’t true replication.
The main difference between COSMOS-Mind and COSMOS-Web is that the former used a telephone interview to administer the cognitive tests and the latter used the Internet. They also had different endpoints, with COSMOS-Web looking at immediate recall rather than a global test composite.
COSMOS-Web was a positive study in that patients getting the multivitamin supplement did better on the test for immediate memory recall (remembering a list of 20 words), though they didn’t improve on tests of memory retention, executive function, or novel object recognition (basically a test where subjects have to identify matching geometric patterns and then recall them later). They were able to remember an additional 0.71 word on average, compared with 0.44 word in the placebo group. (For the record, it found no benefit for the cocoa extract).
Everybody does better on memory tests the second time around because practice makes perfect, hence the improvement in the placebo group. This benefit at 1 year did not survive to the end of follow-up at 3 years, in contrast to COSMOS-Mind, where the benefit was not apparent at 1 year and seen only at year 3. A history of cardiovascular disease didn’t seem to affect the results in COSMOS-Web as it did in COSMOS-Mind. As far as replications go, COSMOS-Web has some very non-negligible differences, compared with COSMOS-Mind. This incongruity, especially given the overlap in the patient populations is hard to reconcile. If COSMOS-Web was supposed to assuage any doubts that persisted after COSMOS-Mind, it hasn’t for me.
One of these studies is not like the others
Finally, although the COSMOS trial and all its ancillary study analyses suggest a neurocognitive benefit to multivitamin supplementation, it’s not the first study to test the matter. The Age-Related Eye Disease Study looked at vitamin C, vitamin E, beta-carotene, zinc, and copper. There was no benefit on any of the six cognitive tests administered to patients. The Women’s Health Study, the Women’s Antioxidant Cardiovascular Study and PREADViSE have all failed to show any benefit to the various vitamins and minerals they studied. A meta-analysis of 11 trials found no benefit to B vitamins in slowing cognitive aging.
The claim that COSMOS is the “first” study to test the hypothesis hinges on some careful wordplay. Prior studies tested specific vitamins, not a multivitamin. In the discussion of the paper, these other studies are critiqued for being short term. But the Physicians’ Health Study II did in fact study a multivitamin and assessed cognitive performance on average 2.5 years after randomization. It found no benefit. The authors of COSMOS-Web critiqued the 2.5-year wait to perform cognitive testing, saying it would have missed any short-term benefits. Although, given that they simultaneously praised their 3 years of follow-up, the criticism is hard to fully accept or even understand.
Whether follow-up is short or long, uses individual vitamins or a multivitamin, the results excluding COSMOS are uniformly negative.
Do enough tests in the same population, and something will rise above the noise just by chance. When you get a positive result in your research, it’s always exciting. But when a slew of studies that came before you are negative, you aren’t groundbreaking. You’re an outlier.
Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
I have written before about the COSMOS study and its finding that multivitamins (and chocolate) did not improve brain or cardiovascular health. So I was surprised to read that a “new” study found that vitamins can forestall dementia and age-related cognitive decline.
Upon closer look, the new data are neither new nor convincing, at least to me.
Chocolate and multivitamins for CVD and cancer prevention
The large randomized COSMOS trial was supposed to be the definitive study on chocolate that would establish its heart-health benefits without a doubt. Or, rather, the benefits of a cocoa bean extract in pill form given to healthy, older volunteers. The COSMOS study was negative. Chocolate, or the cocoa bean extract they used, did not reduce cardiovascular events.
And yet for all the prepublication importance attached to COSMOS, it is scarcely mentioned. Had it been positive, rest assured that Mars, the candy bar company that cofunded the research, and other interested parties would have been shouting it from the rooftops. As it is, they’re already spinning it.
Which brings us to the multivitamin component. COSMOS actually had a 2 × 2 design. In other words, there were four groups in this study: chocolate plus multivitamin, chocolate plus placebo, placebo plus multivitamin, and placebo plus placebo. This type of study design allows you to study two different interventions simultaneously, provided that they are independent and do not interact with each other. In addition to the primary cardiovascular endpoint, they also studied a cancer endpoint.
The multivitamin supplement didn’t reduce cardiovascular events either. Nor did it affect cancer outcomes. The main COSMOS study was negative and reinforced what countless other studies have proven: Taking a daily multivitamin does not reduce your risk of having a heart attack or developing cancer.
But wait, there’s more: COSMOS-Mind
But no researcher worth his salt studies just one or two endpoints in a study. The participants also underwent neurologic and memory testing. These results were reported separately in the COSMOS-Mind study.
COSMOS-Mind is often described as a separate (or “new”) study. In reality, it included the same participants from the original COSMOS trial and measured yet another primary outcome of cognitive performance on a series of tests administered by telephone. Although there is nothing inherently wrong with studying multiple outcomes in your patient population (after all, that salami isn’t going to slice itself), they cannot all be primary outcomes. Some, by necessity, must be secondary hypothesis–generating outcomes. If you test enough endpoints, multiple hypothesis testing dictates that eventually you will get a positive result simply by chance.
There was a time when the neurocognitive outcomes of COSMOS would have been reported in the same paper as the cardiovascular outcomes, but that time seems to have passed us by. Researchers live or die by the number of their publications, and there is an inherent advantage to squeezing as many publications as possible from the same dataset. Though, to be fair, the journal would probably have asked them to split up the paper as well.
In brief, the cocoa extract again fell short in COSMOS-Mind, but the multivitamin arm did better on the composite cognitive outcome. It was a fairly small difference – a 0.07-point improvement on the z-score at the 3-year mark (the z-score is the mean divided by the standard deviation). Much was also made of the fact that the improvement seemed to vary by prior history of cardiovascular disease (CVD). Those with a history of CVD had a 0.11-point improvement, whereas those without had a 0.06-point improvement. The authors couldn’t offer a definitive explanation for these findings. Any argument that multivitamins improve cardiovascular health and therefore prevent vascular dementia has to contend with the fact that the main COSMOS study didn’t show a cardiovascular benefit for vitamins. Speculation that you are treating nutritional deficiencies is exactly that: speculation.
A more salient question is: What does a 0.07-point improvement on the z-score mean clinically? This study didn’t assess whether a multivitamin supplement prevented dementia or allowed people to live independently for longer. In fairness, that would have been exceptionally difficult to do and would have required a much longer study.
Their one attempt to quantify the cognitive benefit clinically was a calculation about normal age-related decline. Test scores were 0.045 points lower for every 1-year increase in age among participants (their mean age was 73 years). So the authors contend that a 0.07-point increase, or the 0.083-point increase that they found at year 3, corresponds to 1.8 years of age-related decline forestalled. Whether this is an appropriate assumption, I leave for the reader to decide.
COSMOS-Web and replication
The results of COSMOS-Mind were seemingly bolstered by the recent publication of COSMOS-Web. Although I’ve seen this study described as having replicated the results of COSMOS-Mind, that description is a bit misleading. This was yet another ancillary COSMOS study; more than half of the 2,262 participants in COSMOS-Mind were also included in COSMOS-Web. Replicating results in the same people isn’t true replication.
The main difference between COSMOS-Mind and COSMOS-Web is that the former used a telephone interview to administer the cognitive tests and the latter used the Internet. They also had different endpoints, with COSMOS-Web looking at immediate recall rather than a global test composite.
COSMOS-Web was a positive study in that patients getting the multivitamin supplement did better on the test for immediate memory recall (remembering a list of 20 words), though they didn’t improve on tests of memory retention, executive function, or novel object recognition (basically a test where subjects have to identify matching geometric patterns and then recall them later). They were able to remember an additional 0.71 word on average, compared with 0.44 word in the placebo group. (For the record, it found no benefit for the cocoa extract).
Everybody does better on memory tests the second time around because practice makes perfect, hence the improvement in the placebo group. This benefit at 1 year did not survive to the end of follow-up at 3 years, in contrast to COSMOS-Mind, where the benefit was not apparent at 1 year and seen only at year 3. A history of cardiovascular disease didn’t seem to affect the results in COSMOS-Web as it did in COSMOS-Mind. As far as replications go, COSMOS-Web has some very non-negligible differences, compared with COSMOS-Mind. This incongruity, especially given the overlap in the patient populations is hard to reconcile. If COSMOS-Web was supposed to assuage any doubts that persisted after COSMOS-Mind, it hasn’t for me.
One of these studies is not like the others
Finally, although the COSMOS trial and all its ancillary study analyses suggest a neurocognitive benefit to multivitamin supplementation, it’s not the first study to test the matter. The Age-Related Eye Disease Study looked at vitamin C, vitamin E, beta-carotene, zinc, and copper. There was no benefit on any of the six cognitive tests administered to patients. The Women’s Health Study, the Women’s Antioxidant Cardiovascular Study and PREADViSE have all failed to show any benefit to the various vitamins and minerals they studied. A meta-analysis of 11 trials found no benefit to B vitamins in slowing cognitive aging.
The claim that COSMOS is the “first” study to test the hypothesis hinges on some careful wordplay. Prior studies tested specific vitamins, not a multivitamin. In the discussion of the paper, these other studies are critiqued for being short term. But the Physicians’ Health Study II did in fact study a multivitamin and assessed cognitive performance on average 2.5 years after randomization. It found no benefit. The authors of COSMOS-Web critiqued the 2.5-year wait to perform cognitive testing, saying it would have missed any short-term benefits. Although, given that they simultaneously praised their 3 years of follow-up, the criticism is hard to fully accept or even understand.
Whether follow-up is short or long, uses individual vitamins or a multivitamin, the results excluding COSMOS are uniformly negative.
Do enough tests in the same population, and something will rise above the noise just by chance. When you get a positive result in your research, it’s always exciting. But when a slew of studies that came before you are negative, you aren’t groundbreaking. You’re an outlier.
Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
I have written before about the COSMOS study and its finding that multivitamins (and chocolate) did not improve brain or cardiovascular health. So I was surprised to read that a “new” study found that vitamins can forestall dementia and age-related cognitive decline.
Upon closer look, the new data are neither new nor convincing, at least to me.
Chocolate and multivitamins for CVD and cancer prevention
The large randomized COSMOS trial was supposed to be the definitive study on chocolate that would establish its heart-health benefits without a doubt. Or, rather, the benefits of a cocoa bean extract in pill form given to healthy, older volunteers. The COSMOS study was negative. Chocolate, or the cocoa bean extract they used, did not reduce cardiovascular events.
And yet for all the prepublication importance attached to COSMOS, it is scarcely mentioned. Had it been positive, rest assured that Mars, the candy bar company that cofunded the research, and other interested parties would have been shouting it from the rooftops. As it is, they’re already spinning it.
Which brings us to the multivitamin component. COSMOS actually had a 2 × 2 design. In other words, there were four groups in this study: chocolate plus multivitamin, chocolate plus placebo, placebo plus multivitamin, and placebo plus placebo. This type of study design allows you to study two different interventions simultaneously, provided that they are independent and do not interact with each other. In addition to the primary cardiovascular endpoint, they also studied a cancer endpoint.
The multivitamin supplement didn’t reduce cardiovascular events either. Nor did it affect cancer outcomes. The main COSMOS study was negative and reinforced what countless other studies have proven: Taking a daily multivitamin does not reduce your risk of having a heart attack or developing cancer.
But wait, there’s more: COSMOS-Mind
But no researcher worth his salt studies just one or two endpoints in a study. The participants also underwent neurologic and memory testing. These results were reported separately in the COSMOS-Mind study.
COSMOS-Mind is often described as a separate (or “new”) study. In reality, it included the same participants from the original COSMOS trial and measured yet another primary outcome of cognitive performance on a series of tests administered by telephone. Although there is nothing inherently wrong with studying multiple outcomes in your patient population (after all, that salami isn’t going to slice itself), they cannot all be primary outcomes. Some, by necessity, must be secondary hypothesis–generating outcomes. If you test enough endpoints, multiple hypothesis testing dictates that eventually you will get a positive result simply by chance.
There was a time when the neurocognitive outcomes of COSMOS would have been reported in the same paper as the cardiovascular outcomes, but that time seems to have passed us by. Researchers live or die by the number of their publications, and there is an inherent advantage to squeezing as many publications as possible from the same dataset. Though, to be fair, the journal would probably have asked them to split up the paper as well.
In brief, the cocoa extract again fell short in COSMOS-Mind, but the multivitamin arm did better on the composite cognitive outcome. It was a fairly small difference – a 0.07-point improvement on the z-score at the 3-year mark (the z-score is the mean divided by the standard deviation). Much was also made of the fact that the improvement seemed to vary by prior history of cardiovascular disease (CVD). Those with a history of CVD had a 0.11-point improvement, whereas those without had a 0.06-point improvement. The authors couldn’t offer a definitive explanation for these findings. Any argument that multivitamins improve cardiovascular health and therefore prevent vascular dementia has to contend with the fact that the main COSMOS study didn’t show a cardiovascular benefit for vitamins. Speculation that you are treating nutritional deficiencies is exactly that: speculation.
A more salient question is: What does a 0.07-point improvement on the z-score mean clinically? This study didn’t assess whether a multivitamin supplement prevented dementia or allowed people to live independently for longer. In fairness, that would have been exceptionally difficult to do and would have required a much longer study.
Their one attempt to quantify the cognitive benefit clinically was a calculation about normal age-related decline. Test scores were 0.045 points lower for every 1-year increase in age among participants (their mean age was 73 years). So the authors contend that a 0.07-point increase, or the 0.083-point increase that they found at year 3, corresponds to 1.8 years of age-related decline forestalled. Whether this is an appropriate assumption, I leave for the reader to decide.
COSMOS-Web and replication
The results of COSMOS-Mind were seemingly bolstered by the recent publication of COSMOS-Web. Although I’ve seen this study described as having replicated the results of COSMOS-Mind, that description is a bit misleading. This was yet another ancillary COSMOS study; more than half of the 2,262 participants in COSMOS-Mind were also included in COSMOS-Web. Replicating results in the same people isn’t true replication.
The main difference between COSMOS-Mind and COSMOS-Web is that the former used a telephone interview to administer the cognitive tests and the latter used the Internet. They also had different endpoints, with COSMOS-Web looking at immediate recall rather than a global test composite.
COSMOS-Web was a positive study in that patients getting the multivitamin supplement did better on the test for immediate memory recall (remembering a list of 20 words), though they didn’t improve on tests of memory retention, executive function, or novel object recognition (basically a test where subjects have to identify matching geometric patterns and then recall them later). They were able to remember an additional 0.71 word on average, compared with 0.44 word in the placebo group. (For the record, it found no benefit for the cocoa extract).
Everybody does better on memory tests the second time around because practice makes perfect, hence the improvement in the placebo group. This benefit at 1 year did not survive to the end of follow-up at 3 years, in contrast to COSMOS-Mind, where the benefit was not apparent at 1 year and seen only at year 3. A history of cardiovascular disease didn’t seem to affect the results in COSMOS-Web as it did in COSMOS-Mind. As far as replications go, COSMOS-Web has some very non-negligible differences, compared with COSMOS-Mind. This incongruity, especially given the overlap in the patient populations is hard to reconcile. If COSMOS-Web was supposed to assuage any doubts that persisted after COSMOS-Mind, it hasn’t for me.
One of these studies is not like the others
Finally, although the COSMOS trial and all its ancillary study analyses suggest a neurocognitive benefit to multivitamin supplementation, it’s not the first study to test the matter. The Age-Related Eye Disease Study looked at vitamin C, vitamin E, beta-carotene, zinc, and copper. There was no benefit on any of the six cognitive tests administered to patients. The Women’s Health Study, the Women’s Antioxidant Cardiovascular Study and PREADViSE have all failed to show any benefit to the various vitamins and minerals they studied. A meta-analysis of 11 trials found no benefit to B vitamins in slowing cognitive aging.
The claim that COSMOS is the “first” study to test the hypothesis hinges on some careful wordplay. Prior studies tested specific vitamins, not a multivitamin. In the discussion of the paper, these other studies are critiqued for being short term. But the Physicians’ Health Study II did in fact study a multivitamin and assessed cognitive performance on average 2.5 years after randomization. It found no benefit. The authors of COSMOS-Web critiqued the 2.5-year wait to perform cognitive testing, saying it would have missed any short-term benefits. Although, given that they simultaneously praised their 3 years of follow-up, the criticism is hard to fully accept or even understand.
Whether follow-up is short or long, uses individual vitamins or a multivitamin, the results excluding COSMOS are uniformly negative.
Do enough tests in the same population, and something will rise above the noise just by chance. When you get a positive result in your research, it’s always exciting. But when a slew of studies that came before you are negative, you aren’t groundbreaking. You’re an outlier.
Dr. Labos is a cardiologist at Hôpital Notre-Dame, Montreal. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
AHA updates CPR guidelines on cardiac arrest after poisoning
The update reflects treatment advances and new knowledge, including the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for patients whose condition is refractory to poison antidotes and other therapies.
The new guidelines are designed primarily for North American health care professionals who treat adults and children who are critically ill because of poisoning, including intentional and unintentional drug overdose, chemical exposure, and drug-drug interactions, the authors note.
Published online in Circulation, the update was endorsed by the American Academy of Pediatrics.
‘Nearly miraculous’
“It’s been 13 years since the poisoning treatment guidelines had a comprehensive update,” lead author Eric J. Lavonas, MD, professor of emergency medicine at Denver Health and the Rocky Mountain Poison and Drug Center, Colo., told this news organization. “In that time, we’ve learned a lot about how to best use antidotes and other treatments to save the most critically poisoned patients.”
Highlighting a few key points from the update, he said, “For those rare situations when antidotes aren’t enough, the new guidelines include the use of heart-lung machines (VA-ECMO) for patients with beta-blocker, calcium channel blocker, or sodium channel blocker poisoning causing cardiogenic shock.”
Furthermore, he said, “High-dose insulin treatment for patients with beta-blocker and calcium channel blocker poisoning [also recommended in the update] has really become mainstream. The doses are up to 10 times higher than the amount used to treat diabetic emergencies.
“Some excellent science has shown that giving IV lipid emulsion can save the life of someone with an accidental overdose of local anesthetic medications, particularly bupivacaine,” he added. “The result is sometimes nearly miraculous.
“But when this treatment is extended to poisoning from other medications, it often doesn’t work as well, and in some situations may make things worse,” he said. “The issue may be that giving lipids increases absorption of drug from the stomach and intestines, which can be dangerous when the patient took an overdose of pills.”
Low level of evidence
The guidelines were compiled by the Critical Poisoning Writing Group, which includes experts from emergency medicine, pediatrics, medical toxicology, pharmacology, critical care, emergency medical services, education, research, and nursing. Group members were appointed by the AHA Emergency Cardiovascular Care Science Subcommittee and were approved by the AHA Manuscript Oversight Committee.
First and foremost, the group recommends timely consultation with a medical toxicologist, a clinical toxicologist, or a regional poison center to facilitate rapid, effective therapy, because treatment of cardiac arrest and toxicity from poisoning often requires treatments that most clinicians don’t use frequently.
Other key points include the following:
- Naloxone administration may reverse respiratory arrest due to opioid overdose, preventing progression to cardiac arrest.
- Give high-dose insulin therapy early in the treatment of patients with beta-blocker and calcium channel blocker poisoning, Dr. Lavonas noted.
- Standard advanced life support plus sodium bicarbonate is appropriate for life-threatening dysrhythmias caused by cocaine or other sodium channel blockers.
- If cyanide poisoning is suspected, clinicians should not wait for confirmatory testing; treatment should begin immediately with hydroxocobalamin (preferred) or sodium nitrite plus sodium thiosulfate.
- Digoxin-specific immune antibody fragments can reverse life-threatening dysrhythmias from digoxin poisoning.
- Use of 20% intravenous lipid emulsion can be efficacious in the resuscitation of life-threatening local anesthetic toxicity, especially from bupivacaine, Dr. Lavonas indicated.
- Sedation is recommended for patients with severe agitation from sympathomimetic poisoning to manage hyperthermia and acidosis, prevent rhabdomyolysis and injury, and allow evaluation for other life-threatening conditions.
- Although flumazenil reverses central nervous system and respiratory depression from benzodiazepine poisoning, risks and contraindications, provided in the guidelines, limit its use.
- VA-ECMO can be lifesaving for patients with cardiogenic shock or dysrhythmias that are refractory to other treatments.
“Unfortunately, despite improvements in the design and funding support for resuscitation research, the overall certainty of the evidence base for resuscitation science and management of critical poisoning is low,” the group acknowledges.
Of the 73 guideline recommendations, only 2 are supported by level A evidence; 3 are supported by level B-randomized evidence, 12 by level B-nonrandomized evidence, and the rest by level C evidence.
“Accordingly, the strength of recommendations is weaker than optimal,” they write. “Clinical trials in resuscitation and the management of critical poisoning are sorely needed.”
‘Don’t go it alone!’
“Most critical poisonings are pretty uncommon, and each patient is different,” Dr. Lavonas said. “Even in the emergency department or ICU, most physicians will treat a patient who is critically ill with any given poison less than once a year. The antidotes and medication doses needed to effectively treat these patients are often very different than everyday medical practice.
“Don’t try to go it alone!” he urges. “Poisoning cases are complex, and the treatments work best when they are implemented quickly and assertively. A toxicologist can help sort through complex situations and get effective treatment started without delay.”
Every certified poison center has a medical toxicologist or clinical toxicologist on call 24/7 to give advice to physicians and hospitals about patients who are critically ill after being poisoned, he added. “Everyone in the U.S. has access to a poison center by calling one number: 1-800-222-1222.”
Dr. Lavonas has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The update reflects treatment advances and new knowledge, including the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for patients whose condition is refractory to poison antidotes and other therapies.
The new guidelines are designed primarily for North American health care professionals who treat adults and children who are critically ill because of poisoning, including intentional and unintentional drug overdose, chemical exposure, and drug-drug interactions, the authors note.
Published online in Circulation, the update was endorsed by the American Academy of Pediatrics.
‘Nearly miraculous’
“It’s been 13 years since the poisoning treatment guidelines had a comprehensive update,” lead author Eric J. Lavonas, MD, professor of emergency medicine at Denver Health and the Rocky Mountain Poison and Drug Center, Colo., told this news organization. “In that time, we’ve learned a lot about how to best use antidotes and other treatments to save the most critically poisoned patients.”
Highlighting a few key points from the update, he said, “For those rare situations when antidotes aren’t enough, the new guidelines include the use of heart-lung machines (VA-ECMO) for patients with beta-blocker, calcium channel blocker, or sodium channel blocker poisoning causing cardiogenic shock.”
Furthermore, he said, “High-dose insulin treatment for patients with beta-blocker and calcium channel blocker poisoning [also recommended in the update] has really become mainstream. The doses are up to 10 times higher than the amount used to treat diabetic emergencies.
“Some excellent science has shown that giving IV lipid emulsion can save the life of someone with an accidental overdose of local anesthetic medications, particularly bupivacaine,” he added. “The result is sometimes nearly miraculous.
“But when this treatment is extended to poisoning from other medications, it often doesn’t work as well, and in some situations may make things worse,” he said. “The issue may be that giving lipids increases absorption of drug from the stomach and intestines, which can be dangerous when the patient took an overdose of pills.”
Low level of evidence
The guidelines were compiled by the Critical Poisoning Writing Group, which includes experts from emergency medicine, pediatrics, medical toxicology, pharmacology, critical care, emergency medical services, education, research, and nursing. Group members were appointed by the AHA Emergency Cardiovascular Care Science Subcommittee and were approved by the AHA Manuscript Oversight Committee.
First and foremost, the group recommends timely consultation with a medical toxicologist, a clinical toxicologist, or a regional poison center to facilitate rapid, effective therapy, because treatment of cardiac arrest and toxicity from poisoning often requires treatments that most clinicians don’t use frequently.
Other key points include the following:
- Naloxone administration may reverse respiratory arrest due to opioid overdose, preventing progression to cardiac arrest.
- Give high-dose insulin therapy early in the treatment of patients with beta-blocker and calcium channel blocker poisoning, Dr. Lavonas noted.
- Standard advanced life support plus sodium bicarbonate is appropriate for life-threatening dysrhythmias caused by cocaine or other sodium channel blockers.
- If cyanide poisoning is suspected, clinicians should not wait for confirmatory testing; treatment should begin immediately with hydroxocobalamin (preferred) or sodium nitrite plus sodium thiosulfate.
- Digoxin-specific immune antibody fragments can reverse life-threatening dysrhythmias from digoxin poisoning.
- Use of 20% intravenous lipid emulsion can be efficacious in the resuscitation of life-threatening local anesthetic toxicity, especially from bupivacaine, Dr. Lavonas indicated.
- Sedation is recommended for patients with severe agitation from sympathomimetic poisoning to manage hyperthermia and acidosis, prevent rhabdomyolysis and injury, and allow evaluation for other life-threatening conditions.
- Although flumazenil reverses central nervous system and respiratory depression from benzodiazepine poisoning, risks and contraindications, provided in the guidelines, limit its use.
- VA-ECMO can be lifesaving for patients with cardiogenic shock or dysrhythmias that are refractory to other treatments.
“Unfortunately, despite improvements in the design and funding support for resuscitation research, the overall certainty of the evidence base for resuscitation science and management of critical poisoning is low,” the group acknowledges.
Of the 73 guideline recommendations, only 2 are supported by level A evidence; 3 are supported by level B-randomized evidence, 12 by level B-nonrandomized evidence, and the rest by level C evidence.
“Accordingly, the strength of recommendations is weaker than optimal,” they write. “Clinical trials in resuscitation and the management of critical poisoning are sorely needed.”
‘Don’t go it alone!’
“Most critical poisonings are pretty uncommon, and each patient is different,” Dr. Lavonas said. “Even in the emergency department or ICU, most physicians will treat a patient who is critically ill with any given poison less than once a year. The antidotes and medication doses needed to effectively treat these patients are often very different than everyday medical practice.
“Don’t try to go it alone!” he urges. “Poisoning cases are complex, and the treatments work best when they are implemented quickly and assertively. A toxicologist can help sort through complex situations and get effective treatment started without delay.”
Every certified poison center has a medical toxicologist or clinical toxicologist on call 24/7 to give advice to physicians and hospitals about patients who are critically ill after being poisoned, he added. “Everyone in the U.S. has access to a poison center by calling one number: 1-800-222-1222.”
Dr. Lavonas has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
The update reflects treatment advances and new knowledge, including the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) for patients whose condition is refractory to poison antidotes and other therapies.
The new guidelines are designed primarily for North American health care professionals who treat adults and children who are critically ill because of poisoning, including intentional and unintentional drug overdose, chemical exposure, and drug-drug interactions, the authors note.
Published online in Circulation, the update was endorsed by the American Academy of Pediatrics.
‘Nearly miraculous’
“It’s been 13 years since the poisoning treatment guidelines had a comprehensive update,” lead author Eric J. Lavonas, MD, professor of emergency medicine at Denver Health and the Rocky Mountain Poison and Drug Center, Colo., told this news organization. “In that time, we’ve learned a lot about how to best use antidotes and other treatments to save the most critically poisoned patients.”
Highlighting a few key points from the update, he said, “For those rare situations when antidotes aren’t enough, the new guidelines include the use of heart-lung machines (VA-ECMO) for patients with beta-blocker, calcium channel blocker, or sodium channel blocker poisoning causing cardiogenic shock.”
Furthermore, he said, “High-dose insulin treatment for patients with beta-blocker and calcium channel blocker poisoning [also recommended in the update] has really become mainstream. The doses are up to 10 times higher than the amount used to treat diabetic emergencies.
“Some excellent science has shown that giving IV lipid emulsion can save the life of someone with an accidental overdose of local anesthetic medications, particularly bupivacaine,” he added. “The result is sometimes nearly miraculous.
“But when this treatment is extended to poisoning from other medications, it often doesn’t work as well, and in some situations may make things worse,” he said. “The issue may be that giving lipids increases absorption of drug from the stomach and intestines, which can be dangerous when the patient took an overdose of pills.”
Low level of evidence
The guidelines were compiled by the Critical Poisoning Writing Group, which includes experts from emergency medicine, pediatrics, medical toxicology, pharmacology, critical care, emergency medical services, education, research, and nursing. Group members were appointed by the AHA Emergency Cardiovascular Care Science Subcommittee and were approved by the AHA Manuscript Oversight Committee.
First and foremost, the group recommends timely consultation with a medical toxicologist, a clinical toxicologist, or a regional poison center to facilitate rapid, effective therapy, because treatment of cardiac arrest and toxicity from poisoning often requires treatments that most clinicians don’t use frequently.
Other key points include the following:
- Naloxone administration may reverse respiratory arrest due to opioid overdose, preventing progression to cardiac arrest.
- Give high-dose insulin therapy early in the treatment of patients with beta-blocker and calcium channel blocker poisoning, Dr. Lavonas noted.
- Standard advanced life support plus sodium bicarbonate is appropriate for life-threatening dysrhythmias caused by cocaine or other sodium channel blockers.
- If cyanide poisoning is suspected, clinicians should not wait for confirmatory testing; treatment should begin immediately with hydroxocobalamin (preferred) or sodium nitrite plus sodium thiosulfate.
- Digoxin-specific immune antibody fragments can reverse life-threatening dysrhythmias from digoxin poisoning.
- Use of 20% intravenous lipid emulsion can be efficacious in the resuscitation of life-threatening local anesthetic toxicity, especially from bupivacaine, Dr. Lavonas indicated.
- Sedation is recommended for patients with severe agitation from sympathomimetic poisoning to manage hyperthermia and acidosis, prevent rhabdomyolysis and injury, and allow evaluation for other life-threatening conditions.
- Although flumazenil reverses central nervous system and respiratory depression from benzodiazepine poisoning, risks and contraindications, provided in the guidelines, limit its use.
- VA-ECMO can be lifesaving for patients with cardiogenic shock or dysrhythmias that are refractory to other treatments.
“Unfortunately, despite improvements in the design and funding support for resuscitation research, the overall certainty of the evidence base for resuscitation science and management of critical poisoning is low,” the group acknowledges.
Of the 73 guideline recommendations, only 2 are supported by level A evidence; 3 are supported by level B-randomized evidence, 12 by level B-nonrandomized evidence, and the rest by level C evidence.
“Accordingly, the strength of recommendations is weaker than optimal,” they write. “Clinical trials in resuscitation and the management of critical poisoning are sorely needed.”
‘Don’t go it alone!’
“Most critical poisonings are pretty uncommon, and each patient is different,” Dr. Lavonas said. “Even in the emergency department or ICU, most physicians will treat a patient who is critically ill with any given poison less than once a year. The antidotes and medication doses needed to effectively treat these patients are often very different than everyday medical practice.
“Don’t try to go it alone!” he urges. “Poisoning cases are complex, and the treatments work best when they are implemented quickly and assertively. A toxicologist can help sort through complex situations and get effective treatment started without delay.”
Every certified poison center has a medical toxicologist or clinical toxicologist on call 24/7 to give advice to physicians and hospitals about patients who are critically ill after being poisoned, he added. “Everyone in the U.S. has access to a poison center by calling one number: 1-800-222-1222.”
Dr. Lavonas has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Data Trends 2023: Cardiology
- Dhruva SS et al. J Gen Intern Med. 2022;37(suppl 3):806-815. doi:10.1007/s11606-022-07595-1
- Han JK et al. Circulation. 2019;139(8):1102-1109. doi:10.1161/CIRCULATIONAHA.118.037748
- Hinojosa R. Chronic Illn. 2020;16(1):55-68. doi:10.1177/1742395318785237
- Lee MT et al. JAMA Cardiol. 2021;6(7):782-790. doi:10.1001/jamacardio.2021.0683
- Gaffey AE et al. Health Psychol. 2021;40(11):737-746. doi:10.1037/hea0001110
- Dhruva SS et al. J Gen Intern Med. 2022;37(suppl 3):806-815. doi:10.1007/s11606-022-07595-1
- Han JK et al. Circulation. 2019;139(8):1102-1109. doi:10.1161/CIRCULATIONAHA.118.037748
- Hinojosa R. Chronic Illn. 2020;16(1):55-68. doi:10.1177/1742395318785237
- Lee MT et al. JAMA Cardiol. 2021;6(7):782-790. doi:10.1001/jamacardio.2021.0683
- Gaffey AE et al. Health Psychol. 2021;40(11):737-746. doi:10.1037/hea0001110
- Dhruva SS et al. J Gen Intern Med. 2022;37(suppl 3):806-815. doi:10.1007/s11606-022-07595-1
- Han JK et al. Circulation. 2019;139(8):1102-1109. doi:10.1161/CIRCULATIONAHA.118.037748
- Hinojosa R. Chronic Illn. 2020;16(1):55-68. doi:10.1177/1742395318785237
- Lee MT et al. JAMA Cardiol. 2021;6(7):782-790. doi:10.1001/jamacardio.2021.0683
- Gaffey AE et al. Health Psychol. 2021;40(11):737-746. doi:10.1037/hea0001110
COVID-19 virus infects coronary vasculature
TOPLINE:
, which could help explain why people with COVID-19 have an increased risk for ischemic cardiovascular complications up to 1 year after infection.
METHODOLOGY:
- Researchers obtained 27 coronary autopsy specimens from eight patients who died from COVID-19, mean age 70 years and 75% male. All had coronary artery disease and most had cardiovascular risk factors such as hypertension, were overweight or obese, and had hyperlipidemia and type 2 diabetes.
- All but one patient, who was pronounced dead before hospital admission, were hospitalized for an average of 17.6 days.
- To identify SARS-CoV-2 viral RNA (vRNA) in the autoptic coronary vasculature, researchers performed RNA fluorescence in situ hybridization (RNA-FISH) analysis for the vRNA encoding the spike (S) protein; they also probed the antisense strand of the S gene (S antisense), which is only produced during viral replication.
TAKEAWAY:
- The study found evidence of SARS-CoV-2 replication in all analyzed human autopsy coronaries regardless of their pathological classification, although viral replication was highest in early-stage lesions that progress to more advanced atherosclerotic plaques.
- Findings indicated that more than 79% of macrophages (white blood cells that help remove lipids) and more than 90% of foam cells (lipid-laden macrophages that are a hallmark of atherosclerosis at all stages of the disease) are S+, and more than 40% of both cell types are S antisense+, indicating SARS-CoV-2 can infect macrophages at a high rate.
- SARS-CoV-2 induced a strong inflammatory response as evidenced by release of cytokines (including interleukin-1 beta and interluekin-6 that are linked to myocardial infarction) in both macrophages and foam cells, which may contribute to the ischemic cardiovascular complications in patients with COVID-19.
IN PRACTICE:
“Our data conclusively demonstrate that SARS-CoV-2 is capable of infecting and replicating in macrophages within the coronary vasculature of patients with COVID-19,” write the authors, adding that SARS-CoV-2 preferentially replicates in foam cells, compared with other macrophages, suggesting these cells “might act as a reservoir of SARS-CoV-2 viral debris in the atherosclerotic plaque.”
SOURCE:
The study was led by Natalia Eberhardt, PhD, postdoctoral fellow, department of medicine, division of cardiology, New York University, and colleagues. It was published online in Nature Cardiovascular Research.
LIMITATIONS:
Findings are relevant only to the original strains of SARS-CoV-2 that circulated in New York between May 2020 and May 2021, and are not generalizable to patients younger and healthier than those from whom samples were obtained for the study.
DISCLOSURES:
The study received support from the National Institutes of Health. The authors report no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
, which could help explain why people with COVID-19 have an increased risk for ischemic cardiovascular complications up to 1 year after infection.
METHODOLOGY:
- Researchers obtained 27 coronary autopsy specimens from eight patients who died from COVID-19, mean age 70 years and 75% male. All had coronary artery disease and most had cardiovascular risk factors such as hypertension, were overweight or obese, and had hyperlipidemia and type 2 diabetes.
- All but one patient, who was pronounced dead before hospital admission, were hospitalized for an average of 17.6 days.
- To identify SARS-CoV-2 viral RNA (vRNA) in the autoptic coronary vasculature, researchers performed RNA fluorescence in situ hybridization (RNA-FISH) analysis for the vRNA encoding the spike (S) protein; they also probed the antisense strand of the S gene (S antisense), which is only produced during viral replication.
TAKEAWAY:
- The study found evidence of SARS-CoV-2 replication in all analyzed human autopsy coronaries regardless of their pathological classification, although viral replication was highest in early-stage lesions that progress to more advanced atherosclerotic plaques.
- Findings indicated that more than 79% of macrophages (white blood cells that help remove lipids) and more than 90% of foam cells (lipid-laden macrophages that are a hallmark of atherosclerosis at all stages of the disease) are S+, and more than 40% of both cell types are S antisense+, indicating SARS-CoV-2 can infect macrophages at a high rate.
- SARS-CoV-2 induced a strong inflammatory response as evidenced by release of cytokines (including interleukin-1 beta and interluekin-6 that are linked to myocardial infarction) in both macrophages and foam cells, which may contribute to the ischemic cardiovascular complications in patients with COVID-19.
IN PRACTICE:
“Our data conclusively demonstrate that SARS-CoV-2 is capable of infecting and replicating in macrophages within the coronary vasculature of patients with COVID-19,” write the authors, adding that SARS-CoV-2 preferentially replicates in foam cells, compared with other macrophages, suggesting these cells “might act as a reservoir of SARS-CoV-2 viral debris in the atherosclerotic plaque.”
SOURCE:
The study was led by Natalia Eberhardt, PhD, postdoctoral fellow, department of medicine, division of cardiology, New York University, and colleagues. It was published online in Nature Cardiovascular Research.
LIMITATIONS:
Findings are relevant only to the original strains of SARS-CoV-2 that circulated in New York between May 2020 and May 2021, and are not generalizable to patients younger and healthier than those from whom samples were obtained for the study.
DISCLOSURES:
The study received support from the National Institutes of Health. The authors report no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
, which could help explain why people with COVID-19 have an increased risk for ischemic cardiovascular complications up to 1 year after infection.
METHODOLOGY:
- Researchers obtained 27 coronary autopsy specimens from eight patients who died from COVID-19, mean age 70 years and 75% male. All had coronary artery disease and most had cardiovascular risk factors such as hypertension, were overweight or obese, and had hyperlipidemia and type 2 diabetes.
- All but one patient, who was pronounced dead before hospital admission, were hospitalized for an average of 17.6 days.
- To identify SARS-CoV-2 viral RNA (vRNA) in the autoptic coronary vasculature, researchers performed RNA fluorescence in situ hybridization (RNA-FISH) analysis for the vRNA encoding the spike (S) protein; they also probed the antisense strand of the S gene (S antisense), which is only produced during viral replication.
TAKEAWAY:
- The study found evidence of SARS-CoV-2 replication in all analyzed human autopsy coronaries regardless of their pathological classification, although viral replication was highest in early-stage lesions that progress to more advanced atherosclerotic plaques.
- Findings indicated that more than 79% of macrophages (white blood cells that help remove lipids) and more than 90% of foam cells (lipid-laden macrophages that are a hallmark of atherosclerosis at all stages of the disease) are S+, and more than 40% of both cell types are S antisense+, indicating SARS-CoV-2 can infect macrophages at a high rate.
- SARS-CoV-2 induced a strong inflammatory response as evidenced by release of cytokines (including interleukin-1 beta and interluekin-6 that are linked to myocardial infarction) in both macrophages and foam cells, which may contribute to the ischemic cardiovascular complications in patients with COVID-19.
IN PRACTICE:
“Our data conclusively demonstrate that SARS-CoV-2 is capable of infecting and replicating in macrophages within the coronary vasculature of patients with COVID-19,” write the authors, adding that SARS-CoV-2 preferentially replicates in foam cells, compared with other macrophages, suggesting these cells “might act as a reservoir of SARS-CoV-2 viral debris in the atherosclerotic plaque.”
SOURCE:
The study was led by Natalia Eberhardt, PhD, postdoctoral fellow, department of medicine, division of cardiology, New York University, and colleagues. It was published online in Nature Cardiovascular Research.
LIMITATIONS:
Findings are relevant only to the original strains of SARS-CoV-2 that circulated in New York between May 2020 and May 2021, and are not generalizable to patients younger and healthier than those from whom samples were obtained for the study.
DISCLOSURES:
The study received support from the National Institutes of Health. The authors report no relevant financial relationships.
A version of this article appeared on Medscape.com.
Factor XI inhibitors: The promise of a truly safe anticoagulant?
The quest to find an anticoagulant that can prevent strokes, cardiovascular events, and venous thrombosis without significantly increasing risk of bleeding is something of a holy grail in cardiovascular medicine. Could the latest focus of interest in this field – the factor XI inhibitors – be the long–sought-after answer?
Topline results from the largest study so far of a factor XI inhibitor – released on Sep. 18 – are indeed very encouraging. The phase 2 AZALEA-TIMI 71 study was stopped early because of an “overwhelming” reduction in major and clinically relevant nonmajor bleeding shown with the factor XI inhibitor abelacimab (Anthos), compared with apixaban for patients with atrial fibrillation (AFib).
Very few other data from this study have yet been released. Full results are due to be presented at the scientific sessions of the American Heart Association in November. Researchers in the field are optimistic that this new class of drugs may allow millions more patients who are at risk of thrombotic events but are concerned about bleeding risk to be treated, with a consequent reduction in strokes and possibly cardiovascular events as well.
Why factor XI?
In natural physiology, there are two ongoing processes: hemostasis – a set of actions that cause bleeding to stop after an injury – and thrombosis – a pathologic clotting process in which thrombus is formed and causes a stroke, MI, or deep venous thrombosis (DVT).
In patients prone to pathologic clotting, such as those with AFib, the balance of these two processes has shifted toward thrombosis, so anticoagulants are used to reduce the thrombotic risks. For many years, the only available oral anticoagulant was warfarin, a vitamin K antagonist that was very effective at preventing strokes but that comes with a high risk for bleeding, including intracranial hemorrhage (ICH) and fatal bleeding.
The introduction of the direct-acting anticoagulants (DOACs) a few years ago was a step forward in that these drugs have been shown to be as effective as warfarin but are associated with a lower risk of bleeding, particularly of ICH and fatal bleeding. But they still cause bleeding, and concerns over that risk of bleeding prevent millions of patients from taking these drugs and receiving protection against stroke.
John Alexander, MD, professor of medicine at Duke University Medical Center, Durham, N.C., a researcher active in this area, notes that “while the DOACs cause less bleeding than warfarin, they still cause two or three times more bleeding than placebo, and there is a huge, unmet need for safer anticoagulants that don’t cause as much bleeding. We are hopeful that factor XI inhibitors might be those anticoagulants.”
The lead investigator the AZALEA study, Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, explained why it is thought that factor XI inhibitors may be different.
“There’s a lot of different clotting factors, and most of them converge in a central pathway. The problem, therefore, with anticoagulants used to date that block one of these factors is that they prevent clotting but also cause bleeding.
“It has been discovered that factor XI has a really unique position in the cascade of how our body forms clots in that it seems to be important in clot formation, but it doesn’t seem to play a major role in our ability to heal and repair blood vessels.”
Another doctor involved in the field, Manesh Patel, MD, chief of cardiology at Duke University Medical Center, added, “We think that factor XI inhibitors may prevent the pathologic formation of thrombosis while allowing formation of thrombus for natural hemostasis to prevent bleeding. That is why they are so promising.”
This correlates with epidemiologic data suggesting that patients with a genetic factor XI deficiency have low rates of stroke and MI but don’t appear to bleed spontaneously, Dr. Patel notes.
Candidates in development
The pharmaceutical industry is on the case with several factor XI inhibitors now in clinical development. At present, three main candidates lead the field. These are abelacimab (Anthos), a monoclonal antibody given by subcutaneous injection once a month; and two small molecules, milvexian (BMS/Janssen) and asundexian (Bayer), which are both given orally.
Phase 3 trials of these three factor XI inhibitors have recently started for a variety of thrombotic indications, including the prevention of stroke in patients with AFib, prevention of recurrent stroke in patients with ischemic stroke, and prevention of future cardiovascular events in patients with acute coronary syndrome (ACS).
Dr. Alexander, who has been involved in clinical trials of both milvexian and asundexian, commented: “We have pretty good data from a number of phase 2 trials now that these factor XI inhibitors at the doses used in these studies cause a lot less bleeding than therapeutic doses of DOACs and low-molecular-weight heparins.”
He pointed out that, in addition to the AZALEA trial with abelacimab, the phase 2 PACIFIC program of studies has shown less bleeding with asundexian than with apixaban in patients with AFib and a similar amount of bleeding as placebo in ACS/stroke patients on top of antiplatelet therapy. Milvexian has also shown similar results in the AXIOMATIC program of studies.
Dr. Ruff noted that the biggest need for new anticoagulants in general is in the AFib population. “Atrial fibrillation is one of the most common medical conditions in the world. Approximately one in every three people will develop AFib in their lifetime, and it is associated with more than a fivefold increased risk of stroke. But up to half of patients with AFib currently do not take anticoagulants because of concerns about bleeding risks, so these patients are being left unprotected from stroke risk.”
Dr. Ruff pointed out that the AZALEA study was the largest and longest study of a factor XI inhibitor to date; 1,287 patients were followed for a median of 2 years.
“This was the first trial of long-term administration of factor XI inhibitor against a full-dose DOAC, and it was stopped because of an overwhelming reduction in a major bleeding with abelacimab, compared with rivaroxaban,” he noted. “That is very encouraging. It looks like our quest to develop a safe anticoagulant with much lower rates of bleeding, compared with standard of care, seems to have been borne out. I think the field is very excited that we may finally have something that protects patients from thrombosis whilst being much safer than current agents.”
While all this sounds very promising, for these drugs to be successful, in addition to reducing bleeding risk, they will also have to be effective at preventing strokes and other thrombotic events.
“While we are pretty sure that factor XI inhibitors will cause less bleeding than current anticoagulants, what is unknown still is how effective they will be at preventing pathologic blood clots,” Dr. Alexander points out.
“We have some data from studies of these drugs in DVT prophylaxis after orthopedic surgery which suggest that they are effective in preventing blood clots in that scenario. But we don’t know yet about whether they can prevent pathologic blood clots that occur in AFib patients or in poststroke or post-ACS patients. Phase 3 studies are now underway with these three leading drug candidates which will answer some of these questions.”
Dr. Patel agrees that the efficacy data in the phase 3 trials will be key to the success of these drugs. “That is a very important part of the puzzle that is still missing,” he says.
Dr. Ruff notes that the AZALEA study will provide some data on efficacy. “But we already know that in the orthopedic surgery trials there was a 70%-80% reduction in VTE with abelacimab (at the 150-mg dose going forward) vs. prophylactic doses of low-molecular-weight heparin. And we know from the DOACs that the doses preventing clots on the venous side also translated into preventing strokes on the [AFib] side. So that is very encouraging,” Dr. Ruff adds.
Potential indications
The three leading factor XI inhibitors have slightly different phase 3 development programs.
Dr. Ruff notes that not every agent is being investigated in phase 3 trials for all the potential indications, but all three are going for the AFib indication. “This is by far the biggest population, the biggest market, and the biggest clinical need for these agents,” he says.
While the milvexian and asundexian trials are using an active comparator – pitting the factor XI inhibitors against apixaban in AFib patients – the Anthos LILAC trial is taking a slightly different approach and is comparing abelacimab with placebo in patients with AFib who are not currently taking an anticoagulant because of concerns about bleeding risk.
Janssen/BMS is conducting two other phase 3 trials of milvexian in their LIBREXIA phase 3 program. Those trials involve poststroke patients and ACS patients. Bayer is also involved in a poststroke trial of asundexian as part of its OCEANIC phase 3 program.
Dr. Ruff points out that anticoagulants currently do not have a large role in the poststroke or post-ACS population. “But the hope is that, if factor XI inhibitors are so safe, then there will be more enthusiasm about using an anticoagulant on top of antiplatelet therapy, which is the cornerstone of therapy in atherosclerotic cardiovascular disease.”
In addition to its phase 3 LILAC study in patients with AFib, Anthos is conducting two major phase 3 trials with abelacimab for the treatment of cancer-associated venous thromboembolism.
Dr. Ruff notes that the indication of postsurgery or general prevention of VTE is not being pursued at present.
“The orthopedic surgery studies were done mainly for dose finding and proof of principle reasons,” he explains. “In orthopedic surgery the window for anticoagulation is quite short – a few weeks or months. And for the prevention of recurrent VTE in general in the community, those people are at a relatively low risk of bleeding, so there may not be much advantage of the factor XI inhibitors, whereas AFib patients and those with stroke or ACS are usually older and have a much higher bleeding risk. I think this is where the advantages of an anticoagulant with a lower bleeding risk are most needed.”
Dr. Alexander points out that to date anticoagulants have shown more efficacy in venous clotting, which appears to be more dependent on coagulation factors and less dependent on platelets. “Atrial fibrillation is a mix between venous and arterial clotting, but it has more similarities to venous, so I think AFib is a place where new anticoagulants such as the factor XI inhibitors are more likely to have success,” he suggests.
“So far, anticoagulants have had a less clear long-term role in the poststroke and post-ACS populations, so these indications may be a more difficult goal,” he added.
The phase 3 studies are just starting and will take a few years before results are known.
Differences between the agents
The three factor XI inhibitors also have some differences. Dr. Ruff points out that most important will be the safety and efficacy of the drugs in phase 3 trials.
“Early data suggest that the various agents being developed may not have equal inhibition of factor XI. The monoclonal antibody abelacimab may produce a higher degree of inhibition than the small molecules. But we don’t know if that matters or not – whether we need to achieve a certain threshold to prevent stroke. The efficacy and safety data from the phase 3 trials are what will primarily guide use.”
There are also differences in formulations and dosage. Abelacimab is administered by subcutaneous injection once a month and has a long duration of activity, whereas the small molecules are taken orally and their duration of action is much shorter.
Dr. Ruff notes: “If these drugs cause bleeding, having a long-acting drug like abelacimab could be a disadvantage because we wouldn’t be able to stop it. But if they are very safe with regard to bleeding, then having the drug hang around for a long time is not necessarily a disadvantage, and it may improve compliance. These older patients often miss doses, and with a shorter-acting drug, that will mean they will be unprotected from stroke risk for a period of time, so there is a trade-off here.”
Dr. Ruff says that the AZALEA phase 2 study will provide some data on patients being managed around procedures. “The hope is that these drugs are so safe that they will not have to be stopped for procedures. And then the compliance issue of a once-a-month dosing would be an advantage.”
Dr. Patel says he believes there is a place for different formations. “Some patients may prefer a once-monthly injection; others will prefer a daily tablet. It may come down to patient preference, but a lot will depend on the study results with the different agents,” he commented.
What effect could these drugs have?
If these drugs do show efficacy in these phase 3 trials, what difference will they make to clinical practice? The potential appears to be very large.
“If these drugs are as effective at preventing strokes as DOACs, they will be a huge breakthrough, and there is good reason to think they would replace the DOACs,” Dr. Alexander says. “It would be a really big deal to have an anticoagulant that causes almost no bleeding and could prevent clots as well as the DOACs. This would enable a lot more patients to receive protection against stroke.”
Dr. Alexander believes the surgery studies are hopeful. “They show that the factor XI inhibitors are doing something to prevent blood clots. The big question is whether they are as effective as what we already have for the prevention of stroke and if not, what is the trade-off with bleeding?”
He points out that, even if the factor XI inhibitors are not as effective as DOACs but are found to be much safer, they might still have a potential clinical role, especially for those patients who currently do not take an anticoagulant because of concerns regarding bleeding.
But Dr. Patel points out that there is always the issue of costs with new drugs. “New drugs are always expensive. The DOACS are just about to become generic, and there will inevitably be concerns about access to an expensive new therapy.”
Dr. Alexander adds: “Yes, costs could be an issue, but a safer drug will definitely help to get more patients treated and in preventing more strokes, which would be a great thing.”
Dr. Patel has received grants from and acts as an adviser to Bayer (asundexian) and Janssen (milvexian). Dr. Alexander receives research funding from Bayer. Dr. Ruff receives research funding from Anthos for abelacimab trials, is on an AFib executive committee for BMS/Janssen, and has been on an advisory board for Bayer.
A version of this article first appeared on Medscape.com.
The quest to find an anticoagulant that can prevent strokes, cardiovascular events, and venous thrombosis without significantly increasing risk of bleeding is something of a holy grail in cardiovascular medicine. Could the latest focus of interest in this field – the factor XI inhibitors – be the long–sought-after answer?
Topline results from the largest study so far of a factor XI inhibitor – released on Sep. 18 – are indeed very encouraging. The phase 2 AZALEA-TIMI 71 study was stopped early because of an “overwhelming” reduction in major and clinically relevant nonmajor bleeding shown with the factor XI inhibitor abelacimab (Anthos), compared with apixaban for patients with atrial fibrillation (AFib).
Very few other data from this study have yet been released. Full results are due to be presented at the scientific sessions of the American Heart Association in November. Researchers in the field are optimistic that this new class of drugs may allow millions more patients who are at risk of thrombotic events but are concerned about bleeding risk to be treated, with a consequent reduction in strokes and possibly cardiovascular events as well.
Why factor XI?
In natural physiology, there are two ongoing processes: hemostasis – a set of actions that cause bleeding to stop after an injury – and thrombosis – a pathologic clotting process in which thrombus is formed and causes a stroke, MI, or deep venous thrombosis (DVT).
In patients prone to pathologic clotting, such as those with AFib, the balance of these two processes has shifted toward thrombosis, so anticoagulants are used to reduce the thrombotic risks. For many years, the only available oral anticoagulant was warfarin, a vitamin K antagonist that was very effective at preventing strokes but that comes with a high risk for bleeding, including intracranial hemorrhage (ICH) and fatal bleeding.
The introduction of the direct-acting anticoagulants (DOACs) a few years ago was a step forward in that these drugs have been shown to be as effective as warfarin but are associated with a lower risk of bleeding, particularly of ICH and fatal bleeding. But they still cause bleeding, and concerns over that risk of bleeding prevent millions of patients from taking these drugs and receiving protection against stroke.
John Alexander, MD, professor of medicine at Duke University Medical Center, Durham, N.C., a researcher active in this area, notes that “while the DOACs cause less bleeding than warfarin, they still cause two or three times more bleeding than placebo, and there is a huge, unmet need for safer anticoagulants that don’t cause as much bleeding. We are hopeful that factor XI inhibitors might be those anticoagulants.”
The lead investigator the AZALEA study, Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, explained why it is thought that factor XI inhibitors may be different.
“There’s a lot of different clotting factors, and most of them converge in a central pathway. The problem, therefore, with anticoagulants used to date that block one of these factors is that they prevent clotting but also cause bleeding.
“It has been discovered that factor XI has a really unique position in the cascade of how our body forms clots in that it seems to be important in clot formation, but it doesn’t seem to play a major role in our ability to heal and repair blood vessels.”
Another doctor involved in the field, Manesh Patel, MD, chief of cardiology at Duke University Medical Center, added, “We think that factor XI inhibitors may prevent the pathologic formation of thrombosis while allowing formation of thrombus for natural hemostasis to prevent bleeding. That is why they are so promising.”
This correlates with epidemiologic data suggesting that patients with a genetic factor XI deficiency have low rates of stroke and MI but don’t appear to bleed spontaneously, Dr. Patel notes.
Candidates in development
The pharmaceutical industry is on the case with several factor XI inhibitors now in clinical development. At present, three main candidates lead the field. These are abelacimab (Anthos), a monoclonal antibody given by subcutaneous injection once a month; and two small molecules, milvexian (BMS/Janssen) and asundexian (Bayer), which are both given orally.
Phase 3 trials of these three factor XI inhibitors have recently started for a variety of thrombotic indications, including the prevention of stroke in patients with AFib, prevention of recurrent stroke in patients with ischemic stroke, and prevention of future cardiovascular events in patients with acute coronary syndrome (ACS).
Dr. Alexander, who has been involved in clinical trials of both milvexian and asundexian, commented: “We have pretty good data from a number of phase 2 trials now that these factor XI inhibitors at the doses used in these studies cause a lot less bleeding than therapeutic doses of DOACs and low-molecular-weight heparins.”
He pointed out that, in addition to the AZALEA trial with abelacimab, the phase 2 PACIFIC program of studies has shown less bleeding with asundexian than with apixaban in patients with AFib and a similar amount of bleeding as placebo in ACS/stroke patients on top of antiplatelet therapy. Milvexian has also shown similar results in the AXIOMATIC program of studies.
Dr. Ruff noted that the biggest need for new anticoagulants in general is in the AFib population. “Atrial fibrillation is one of the most common medical conditions in the world. Approximately one in every three people will develop AFib in their lifetime, and it is associated with more than a fivefold increased risk of stroke. But up to half of patients with AFib currently do not take anticoagulants because of concerns about bleeding risks, so these patients are being left unprotected from stroke risk.”
Dr. Ruff pointed out that the AZALEA study was the largest and longest study of a factor XI inhibitor to date; 1,287 patients were followed for a median of 2 years.
“This was the first trial of long-term administration of factor XI inhibitor against a full-dose DOAC, and it was stopped because of an overwhelming reduction in a major bleeding with abelacimab, compared with rivaroxaban,” he noted. “That is very encouraging. It looks like our quest to develop a safe anticoagulant with much lower rates of bleeding, compared with standard of care, seems to have been borne out. I think the field is very excited that we may finally have something that protects patients from thrombosis whilst being much safer than current agents.”
While all this sounds very promising, for these drugs to be successful, in addition to reducing bleeding risk, they will also have to be effective at preventing strokes and other thrombotic events.
“While we are pretty sure that factor XI inhibitors will cause less bleeding than current anticoagulants, what is unknown still is how effective they will be at preventing pathologic blood clots,” Dr. Alexander points out.
“We have some data from studies of these drugs in DVT prophylaxis after orthopedic surgery which suggest that they are effective in preventing blood clots in that scenario. But we don’t know yet about whether they can prevent pathologic blood clots that occur in AFib patients or in poststroke or post-ACS patients. Phase 3 studies are now underway with these three leading drug candidates which will answer some of these questions.”
Dr. Patel agrees that the efficacy data in the phase 3 trials will be key to the success of these drugs. “That is a very important part of the puzzle that is still missing,” he says.
Dr. Ruff notes that the AZALEA study will provide some data on efficacy. “But we already know that in the orthopedic surgery trials there was a 70%-80% reduction in VTE with abelacimab (at the 150-mg dose going forward) vs. prophylactic doses of low-molecular-weight heparin. And we know from the DOACs that the doses preventing clots on the venous side also translated into preventing strokes on the [AFib] side. So that is very encouraging,” Dr. Ruff adds.
Potential indications
The three leading factor XI inhibitors have slightly different phase 3 development programs.
Dr. Ruff notes that not every agent is being investigated in phase 3 trials for all the potential indications, but all three are going for the AFib indication. “This is by far the biggest population, the biggest market, and the biggest clinical need for these agents,” he says.
While the milvexian and asundexian trials are using an active comparator – pitting the factor XI inhibitors against apixaban in AFib patients – the Anthos LILAC trial is taking a slightly different approach and is comparing abelacimab with placebo in patients with AFib who are not currently taking an anticoagulant because of concerns about bleeding risk.
Janssen/BMS is conducting two other phase 3 trials of milvexian in their LIBREXIA phase 3 program. Those trials involve poststroke patients and ACS patients. Bayer is also involved in a poststroke trial of asundexian as part of its OCEANIC phase 3 program.
Dr. Ruff points out that anticoagulants currently do not have a large role in the poststroke or post-ACS population. “But the hope is that, if factor XI inhibitors are so safe, then there will be more enthusiasm about using an anticoagulant on top of antiplatelet therapy, which is the cornerstone of therapy in atherosclerotic cardiovascular disease.”
In addition to its phase 3 LILAC study in patients with AFib, Anthos is conducting two major phase 3 trials with abelacimab for the treatment of cancer-associated venous thromboembolism.
Dr. Ruff notes that the indication of postsurgery or general prevention of VTE is not being pursued at present.
“The orthopedic surgery studies were done mainly for dose finding and proof of principle reasons,” he explains. “In orthopedic surgery the window for anticoagulation is quite short – a few weeks or months. And for the prevention of recurrent VTE in general in the community, those people are at a relatively low risk of bleeding, so there may not be much advantage of the factor XI inhibitors, whereas AFib patients and those with stroke or ACS are usually older and have a much higher bleeding risk. I think this is where the advantages of an anticoagulant with a lower bleeding risk are most needed.”
Dr. Alexander points out that to date anticoagulants have shown more efficacy in venous clotting, which appears to be more dependent on coagulation factors and less dependent on platelets. “Atrial fibrillation is a mix between venous and arterial clotting, but it has more similarities to venous, so I think AFib is a place where new anticoagulants such as the factor XI inhibitors are more likely to have success,” he suggests.
“So far, anticoagulants have had a less clear long-term role in the poststroke and post-ACS populations, so these indications may be a more difficult goal,” he added.
The phase 3 studies are just starting and will take a few years before results are known.
Differences between the agents
The three factor XI inhibitors also have some differences. Dr. Ruff points out that most important will be the safety and efficacy of the drugs in phase 3 trials.
“Early data suggest that the various agents being developed may not have equal inhibition of factor XI. The monoclonal antibody abelacimab may produce a higher degree of inhibition than the small molecules. But we don’t know if that matters or not – whether we need to achieve a certain threshold to prevent stroke. The efficacy and safety data from the phase 3 trials are what will primarily guide use.”
There are also differences in formulations and dosage. Abelacimab is administered by subcutaneous injection once a month and has a long duration of activity, whereas the small molecules are taken orally and their duration of action is much shorter.
Dr. Ruff notes: “If these drugs cause bleeding, having a long-acting drug like abelacimab could be a disadvantage because we wouldn’t be able to stop it. But if they are very safe with regard to bleeding, then having the drug hang around for a long time is not necessarily a disadvantage, and it may improve compliance. These older patients often miss doses, and with a shorter-acting drug, that will mean they will be unprotected from stroke risk for a period of time, so there is a trade-off here.”
Dr. Ruff says that the AZALEA phase 2 study will provide some data on patients being managed around procedures. “The hope is that these drugs are so safe that they will not have to be stopped for procedures. And then the compliance issue of a once-a-month dosing would be an advantage.”
Dr. Patel says he believes there is a place for different formations. “Some patients may prefer a once-monthly injection; others will prefer a daily tablet. It may come down to patient preference, but a lot will depend on the study results with the different agents,” he commented.
What effect could these drugs have?
If these drugs do show efficacy in these phase 3 trials, what difference will they make to clinical practice? The potential appears to be very large.
“If these drugs are as effective at preventing strokes as DOACs, they will be a huge breakthrough, and there is good reason to think they would replace the DOACs,” Dr. Alexander says. “It would be a really big deal to have an anticoagulant that causes almost no bleeding and could prevent clots as well as the DOACs. This would enable a lot more patients to receive protection against stroke.”
Dr. Alexander believes the surgery studies are hopeful. “They show that the factor XI inhibitors are doing something to prevent blood clots. The big question is whether they are as effective as what we already have for the prevention of stroke and if not, what is the trade-off with bleeding?”
He points out that, even if the factor XI inhibitors are not as effective as DOACs but are found to be much safer, they might still have a potential clinical role, especially for those patients who currently do not take an anticoagulant because of concerns regarding bleeding.
But Dr. Patel points out that there is always the issue of costs with new drugs. “New drugs are always expensive. The DOACS are just about to become generic, and there will inevitably be concerns about access to an expensive new therapy.”
Dr. Alexander adds: “Yes, costs could be an issue, but a safer drug will definitely help to get more patients treated and in preventing more strokes, which would be a great thing.”
Dr. Patel has received grants from and acts as an adviser to Bayer (asundexian) and Janssen (milvexian). Dr. Alexander receives research funding from Bayer. Dr. Ruff receives research funding from Anthos for abelacimab trials, is on an AFib executive committee for BMS/Janssen, and has been on an advisory board for Bayer.
A version of this article first appeared on Medscape.com.
The quest to find an anticoagulant that can prevent strokes, cardiovascular events, and venous thrombosis without significantly increasing risk of bleeding is something of a holy grail in cardiovascular medicine. Could the latest focus of interest in this field – the factor XI inhibitors – be the long–sought-after answer?
Topline results from the largest study so far of a factor XI inhibitor – released on Sep. 18 – are indeed very encouraging. The phase 2 AZALEA-TIMI 71 study was stopped early because of an “overwhelming” reduction in major and clinically relevant nonmajor bleeding shown with the factor XI inhibitor abelacimab (Anthos), compared with apixaban for patients with atrial fibrillation (AFib).
Very few other data from this study have yet been released. Full results are due to be presented at the scientific sessions of the American Heart Association in November. Researchers in the field are optimistic that this new class of drugs may allow millions more patients who are at risk of thrombotic events but are concerned about bleeding risk to be treated, with a consequent reduction in strokes and possibly cardiovascular events as well.
Why factor XI?
In natural physiology, there are two ongoing processes: hemostasis – a set of actions that cause bleeding to stop after an injury – and thrombosis – a pathologic clotting process in which thrombus is formed and causes a stroke, MI, or deep venous thrombosis (DVT).
In patients prone to pathologic clotting, such as those with AFib, the balance of these two processes has shifted toward thrombosis, so anticoagulants are used to reduce the thrombotic risks. For many years, the only available oral anticoagulant was warfarin, a vitamin K antagonist that was very effective at preventing strokes but that comes with a high risk for bleeding, including intracranial hemorrhage (ICH) and fatal bleeding.
The introduction of the direct-acting anticoagulants (DOACs) a few years ago was a step forward in that these drugs have been shown to be as effective as warfarin but are associated with a lower risk of bleeding, particularly of ICH and fatal bleeding. But they still cause bleeding, and concerns over that risk of bleeding prevent millions of patients from taking these drugs and receiving protection against stroke.
John Alexander, MD, professor of medicine at Duke University Medical Center, Durham, N.C., a researcher active in this area, notes that “while the DOACs cause less bleeding than warfarin, they still cause two or three times more bleeding than placebo, and there is a huge, unmet need for safer anticoagulants that don’t cause as much bleeding. We are hopeful that factor XI inhibitors might be those anticoagulants.”
The lead investigator the AZALEA study, Christian Ruff, MD, professor of medicine at Brigham and Women’s Hospital, Boston, explained why it is thought that factor XI inhibitors may be different.
“There’s a lot of different clotting factors, and most of them converge in a central pathway. The problem, therefore, with anticoagulants used to date that block one of these factors is that they prevent clotting but also cause bleeding.
“It has been discovered that factor XI has a really unique position in the cascade of how our body forms clots in that it seems to be important in clot formation, but it doesn’t seem to play a major role in our ability to heal and repair blood vessels.”
Another doctor involved in the field, Manesh Patel, MD, chief of cardiology at Duke University Medical Center, added, “We think that factor XI inhibitors may prevent the pathologic formation of thrombosis while allowing formation of thrombus for natural hemostasis to prevent bleeding. That is why they are so promising.”
This correlates with epidemiologic data suggesting that patients with a genetic factor XI deficiency have low rates of stroke and MI but don’t appear to bleed spontaneously, Dr. Patel notes.
Candidates in development
The pharmaceutical industry is on the case with several factor XI inhibitors now in clinical development. At present, three main candidates lead the field. These are abelacimab (Anthos), a monoclonal antibody given by subcutaneous injection once a month; and two small molecules, milvexian (BMS/Janssen) and asundexian (Bayer), which are both given orally.
Phase 3 trials of these three factor XI inhibitors have recently started for a variety of thrombotic indications, including the prevention of stroke in patients with AFib, prevention of recurrent stroke in patients with ischemic stroke, and prevention of future cardiovascular events in patients with acute coronary syndrome (ACS).
Dr. Alexander, who has been involved in clinical trials of both milvexian and asundexian, commented: “We have pretty good data from a number of phase 2 trials now that these factor XI inhibitors at the doses used in these studies cause a lot less bleeding than therapeutic doses of DOACs and low-molecular-weight heparins.”
He pointed out that, in addition to the AZALEA trial with abelacimab, the phase 2 PACIFIC program of studies has shown less bleeding with asundexian than with apixaban in patients with AFib and a similar amount of bleeding as placebo in ACS/stroke patients on top of antiplatelet therapy. Milvexian has also shown similar results in the AXIOMATIC program of studies.
Dr. Ruff noted that the biggest need for new anticoagulants in general is in the AFib population. “Atrial fibrillation is one of the most common medical conditions in the world. Approximately one in every three people will develop AFib in their lifetime, and it is associated with more than a fivefold increased risk of stroke. But up to half of patients with AFib currently do not take anticoagulants because of concerns about bleeding risks, so these patients are being left unprotected from stroke risk.”
Dr. Ruff pointed out that the AZALEA study was the largest and longest study of a factor XI inhibitor to date; 1,287 patients were followed for a median of 2 years.
“This was the first trial of long-term administration of factor XI inhibitor against a full-dose DOAC, and it was stopped because of an overwhelming reduction in a major bleeding with abelacimab, compared with rivaroxaban,” he noted. “That is very encouraging. It looks like our quest to develop a safe anticoagulant with much lower rates of bleeding, compared with standard of care, seems to have been borne out. I think the field is very excited that we may finally have something that protects patients from thrombosis whilst being much safer than current agents.”
While all this sounds very promising, for these drugs to be successful, in addition to reducing bleeding risk, they will also have to be effective at preventing strokes and other thrombotic events.
“While we are pretty sure that factor XI inhibitors will cause less bleeding than current anticoagulants, what is unknown still is how effective they will be at preventing pathologic blood clots,” Dr. Alexander points out.
“We have some data from studies of these drugs in DVT prophylaxis after orthopedic surgery which suggest that they are effective in preventing blood clots in that scenario. But we don’t know yet about whether they can prevent pathologic blood clots that occur in AFib patients or in poststroke or post-ACS patients. Phase 3 studies are now underway with these three leading drug candidates which will answer some of these questions.”
Dr. Patel agrees that the efficacy data in the phase 3 trials will be key to the success of these drugs. “That is a very important part of the puzzle that is still missing,” he says.
Dr. Ruff notes that the AZALEA study will provide some data on efficacy. “But we already know that in the orthopedic surgery trials there was a 70%-80% reduction in VTE with abelacimab (at the 150-mg dose going forward) vs. prophylactic doses of low-molecular-weight heparin. And we know from the DOACs that the doses preventing clots on the venous side also translated into preventing strokes on the [AFib] side. So that is very encouraging,” Dr. Ruff adds.
Potential indications
The three leading factor XI inhibitors have slightly different phase 3 development programs.
Dr. Ruff notes that not every agent is being investigated in phase 3 trials for all the potential indications, but all three are going for the AFib indication. “This is by far the biggest population, the biggest market, and the biggest clinical need for these agents,” he says.
While the milvexian and asundexian trials are using an active comparator – pitting the factor XI inhibitors against apixaban in AFib patients – the Anthos LILAC trial is taking a slightly different approach and is comparing abelacimab with placebo in patients with AFib who are not currently taking an anticoagulant because of concerns about bleeding risk.
Janssen/BMS is conducting two other phase 3 trials of milvexian in their LIBREXIA phase 3 program. Those trials involve poststroke patients and ACS patients. Bayer is also involved in a poststroke trial of asundexian as part of its OCEANIC phase 3 program.
Dr. Ruff points out that anticoagulants currently do not have a large role in the poststroke or post-ACS population. “But the hope is that, if factor XI inhibitors are so safe, then there will be more enthusiasm about using an anticoagulant on top of antiplatelet therapy, which is the cornerstone of therapy in atherosclerotic cardiovascular disease.”
In addition to its phase 3 LILAC study in patients with AFib, Anthos is conducting two major phase 3 trials with abelacimab for the treatment of cancer-associated venous thromboembolism.
Dr. Ruff notes that the indication of postsurgery or general prevention of VTE is not being pursued at present.
“The orthopedic surgery studies were done mainly for dose finding and proof of principle reasons,” he explains. “In orthopedic surgery the window for anticoagulation is quite short – a few weeks or months. And for the prevention of recurrent VTE in general in the community, those people are at a relatively low risk of bleeding, so there may not be much advantage of the factor XI inhibitors, whereas AFib patients and those with stroke or ACS are usually older and have a much higher bleeding risk. I think this is where the advantages of an anticoagulant with a lower bleeding risk are most needed.”
Dr. Alexander points out that to date anticoagulants have shown more efficacy in venous clotting, which appears to be more dependent on coagulation factors and less dependent on platelets. “Atrial fibrillation is a mix between venous and arterial clotting, but it has more similarities to venous, so I think AFib is a place where new anticoagulants such as the factor XI inhibitors are more likely to have success,” he suggests.
“So far, anticoagulants have had a less clear long-term role in the poststroke and post-ACS populations, so these indications may be a more difficult goal,” he added.
The phase 3 studies are just starting and will take a few years before results are known.
Differences between the agents
The three factor XI inhibitors also have some differences. Dr. Ruff points out that most important will be the safety and efficacy of the drugs in phase 3 trials.
“Early data suggest that the various agents being developed may not have equal inhibition of factor XI. The monoclonal antibody abelacimab may produce a higher degree of inhibition than the small molecules. But we don’t know if that matters or not – whether we need to achieve a certain threshold to prevent stroke. The efficacy and safety data from the phase 3 trials are what will primarily guide use.”
There are also differences in formulations and dosage. Abelacimab is administered by subcutaneous injection once a month and has a long duration of activity, whereas the small molecules are taken orally and their duration of action is much shorter.
Dr. Ruff notes: “If these drugs cause bleeding, having a long-acting drug like abelacimab could be a disadvantage because we wouldn’t be able to stop it. But if they are very safe with regard to bleeding, then having the drug hang around for a long time is not necessarily a disadvantage, and it may improve compliance. These older patients often miss doses, and with a shorter-acting drug, that will mean they will be unprotected from stroke risk for a period of time, so there is a trade-off here.”
Dr. Ruff says that the AZALEA phase 2 study will provide some data on patients being managed around procedures. “The hope is that these drugs are so safe that they will not have to be stopped for procedures. And then the compliance issue of a once-a-month dosing would be an advantage.”
Dr. Patel says he believes there is a place for different formations. “Some patients may prefer a once-monthly injection; others will prefer a daily tablet. It may come down to patient preference, but a lot will depend on the study results with the different agents,” he commented.
What effect could these drugs have?
If these drugs do show efficacy in these phase 3 trials, what difference will they make to clinical practice? The potential appears to be very large.
“If these drugs are as effective at preventing strokes as DOACs, they will be a huge breakthrough, and there is good reason to think they would replace the DOACs,” Dr. Alexander says. “It would be a really big deal to have an anticoagulant that causes almost no bleeding and could prevent clots as well as the DOACs. This would enable a lot more patients to receive protection against stroke.”
Dr. Alexander believes the surgery studies are hopeful. “They show that the factor XI inhibitors are doing something to prevent blood clots. The big question is whether they are as effective as what we already have for the prevention of stroke and if not, what is the trade-off with bleeding?”
He points out that, even if the factor XI inhibitors are not as effective as DOACs but are found to be much safer, they might still have a potential clinical role, especially for those patients who currently do not take an anticoagulant because of concerns regarding bleeding.
But Dr. Patel points out that there is always the issue of costs with new drugs. “New drugs are always expensive. The DOACS are just about to become generic, and there will inevitably be concerns about access to an expensive new therapy.”
Dr. Alexander adds: “Yes, costs could be an issue, but a safer drug will definitely help to get more patients treated and in preventing more strokes, which would be a great thing.”
Dr. Patel has received grants from and acts as an adviser to Bayer (asundexian) and Janssen (milvexian). Dr. Alexander receives research funding from Bayer. Dr. Ruff receives research funding from Anthos for abelacimab trials, is on an AFib executive committee for BMS/Janssen, and has been on an advisory board for Bayer.
A version of this article first appeared on Medscape.com.
Residential move after a heart attack raises mortality risk
data suggest.
In a prospective study that followed more than 3,000 patients with AMI over 2 decades, each residential move was associated with a 12% higher rate of death.
“This study determined that residential mobility was more important than any other social factor that we studied,” investigator David Alter, MD, PhD, chair of cardiovascular and metabolic research at the University Health Network–Toronto Rehabilitation Institute and associate professor of medicine at the University of Toronto, said in an interview.
The results were published online in the Canadian Journal of Cardiology.
Moving and mortality
“There’s been very little work, surprisingly, on what happens when individuals move from community to community,” said Dr. Alter. “It is that movement from community to community that is a factor within the social context that needs to be explored better. To the best of our knowledge, up until our study, it has been studied very briefly in the literature.”
The prospective cohort study sample included 3,369 patients who had an AMI between Dec. 1, 1999, and March 30, 2023. The investigators followed participants until death or the last available follow-up date of March 30, 2020. They defined a residential move as a relocation from one postal code region to another.
The investigators drew data from multiple sources, including the prospective, observational Socio-Economic Status and Acute Myocardial Infarction study, which encompassed more than 35,000 patient life-years following hospitalization for a first heart attack in Ontario. Mortality data were collected from the Ontario Registered Persons Data Base. Other sources included Statistics Canada for information on neighborhood income, the Canadian Institutes for Health Information for patients’ clinical factors and comorbidities, and the Ontario Health Insurance Plan (OHIP) database for physician visits. Information on long-term care admissions came from the Continuous Care Reporting System-Long Term Care, OHIP, and the Ontario Drugs Benefit databases, the latter of which also provided information on medication prescriptions for individuals aged 65 years and older.
Patients’ ages ranged from 19 to 101 years (median age, 65 years). About 69% of patients were men. Of the study population, 1,828 patients (54.3%) had at least one residential move during the study period. Approximately 87% died in the community or moved from home into a long-term care facility as an end-of-life destination. Overall, 84.8% of patients who were admitted to long-term care facilities died.
The study also tracked the socioeconomic status of persons living in the postal code regions from and to which patients moved. About 32% of patients moved to a neighborhood with a lower socioeconomic status, and 30.5% moved to an area with a higher socioeconomic status.
Each residential move was associated with a 12% higher rate of death and a 26% higher rate of long-term institutionalization for end-of-life care. In unadjusted analyses, the rate of death was almost double for those who moved more frequently: 44.3% for those who moved two or more times versus 24.8% for those who moved once in 10 years.
Accounting for a multitude of variables, such as the socioeconomic status of areas that patients moved between, is a strength of the study, said Dr. Alter. But the study lacked information about why people moved.
“Where this study has a huge amount of strength is that it was designed specifically to really understand a patient’s clinical and psychosocial profile at the start of their journey, their first AMI. But the fact that we took it from heart attack onward is also a strength because it characterizes and anchors a clinical context in which we were following patients out,” said Dr. Alter.
‘An important marker’
In a comment, Paul Oh, MD, medical director of the cardiovascular disease prevention and rehabilitation program at University Health Network, said: “This is a very well-designed study and analysis from a cohort that has provided important insights about the role of socioeconomic factors and long-term outcomes post MI over many years.” Dr. Oh did not participate in the study.
“A few covariates that could impact on outcomes, like institutionalization, were not available to include in adjusted analyses – e.g., functional status, frailty, mild cognitive changes, and availability of social supports in the home,” he said.
The findings add another variable that cardiologists who care for post-MI patients need to be aware of, Dr. Oh added. “Clinicians need better awareness that the need to change residence is an important marker of changing health status and may portend end-of-life events in the near future. The need to change residence can signal an important change in physical, cognitive, and social circumstances that needs to be further explored during clinical encounters, with the goal of identifying and addressing any potentially reversible issues and identifying additional supports that may help that individual continue to live independently in their own home.”
The study was supported by ICES, which receives funding from the Ontario Ministry of Health. The investigators disclosed no relevant financial relationships. Dr. Oh serves on research boards for Lilly and Novartis and receives research funding from Apple.
A version of this article first appeared on Medscape.com.
data suggest.
In a prospective study that followed more than 3,000 patients with AMI over 2 decades, each residential move was associated with a 12% higher rate of death.
“This study determined that residential mobility was more important than any other social factor that we studied,” investigator David Alter, MD, PhD, chair of cardiovascular and metabolic research at the University Health Network–Toronto Rehabilitation Institute and associate professor of medicine at the University of Toronto, said in an interview.
The results were published online in the Canadian Journal of Cardiology.
Moving and mortality
“There’s been very little work, surprisingly, on what happens when individuals move from community to community,” said Dr. Alter. “It is that movement from community to community that is a factor within the social context that needs to be explored better. To the best of our knowledge, up until our study, it has been studied very briefly in the literature.”
The prospective cohort study sample included 3,369 patients who had an AMI between Dec. 1, 1999, and March 30, 2023. The investigators followed participants until death or the last available follow-up date of March 30, 2020. They defined a residential move as a relocation from one postal code region to another.
The investigators drew data from multiple sources, including the prospective, observational Socio-Economic Status and Acute Myocardial Infarction study, which encompassed more than 35,000 patient life-years following hospitalization for a first heart attack in Ontario. Mortality data were collected from the Ontario Registered Persons Data Base. Other sources included Statistics Canada for information on neighborhood income, the Canadian Institutes for Health Information for patients’ clinical factors and comorbidities, and the Ontario Health Insurance Plan (OHIP) database for physician visits. Information on long-term care admissions came from the Continuous Care Reporting System-Long Term Care, OHIP, and the Ontario Drugs Benefit databases, the latter of which also provided information on medication prescriptions for individuals aged 65 years and older.
Patients’ ages ranged from 19 to 101 years (median age, 65 years). About 69% of patients were men. Of the study population, 1,828 patients (54.3%) had at least one residential move during the study period. Approximately 87% died in the community or moved from home into a long-term care facility as an end-of-life destination. Overall, 84.8% of patients who were admitted to long-term care facilities died.
The study also tracked the socioeconomic status of persons living in the postal code regions from and to which patients moved. About 32% of patients moved to a neighborhood with a lower socioeconomic status, and 30.5% moved to an area with a higher socioeconomic status.
Each residential move was associated with a 12% higher rate of death and a 26% higher rate of long-term institutionalization for end-of-life care. In unadjusted analyses, the rate of death was almost double for those who moved more frequently: 44.3% for those who moved two or more times versus 24.8% for those who moved once in 10 years.
Accounting for a multitude of variables, such as the socioeconomic status of areas that patients moved between, is a strength of the study, said Dr. Alter. But the study lacked information about why people moved.
“Where this study has a huge amount of strength is that it was designed specifically to really understand a patient’s clinical and psychosocial profile at the start of their journey, their first AMI. But the fact that we took it from heart attack onward is also a strength because it characterizes and anchors a clinical context in which we were following patients out,” said Dr. Alter.
‘An important marker’
In a comment, Paul Oh, MD, medical director of the cardiovascular disease prevention and rehabilitation program at University Health Network, said: “This is a very well-designed study and analysis from a cohort that has provided important insights about the role of socioeconomic factors and long-term outcomes post MI over many years.” Dr. Oh did not participate in the study.
“A few covariates that could impact on outcomes, like institutionalization, were not available to include in adjusted analyses – e.g., functional status, frailty, mild cognitive changes, and availability of social supports in the home,” he said.
The findings add another variable that cardiologists who care for post-MI patients need to be aware of, Dr. Oh added. “Clinicians need better awareness that the need to change residence is an important marker of changing health status and may portend end-of-life events in the near future. The need to change residence can signal an important change in physical, cognitive, and social circumstances that needs to be further explored during clinical encounters, with the goal of identifying and addressing any potentially reversible issues and identifying additional supports that may help that individual continue to live independently in their own home.”
The study was supported by ICES, which receives funding from the Ontario Ministry of Health. The investigators disclosed no relevant financial relationships. Dr. Oh serves on research boards for Lilly and Novartis and receives research funding from Apple.
A version of this article first appeared on Medscape.com.
data suggest.
In a prospective study that followed more than 3,000 patients with AMI over 2 decades, each residential move was associated with a 12% higher rate of death.
“This study determined that residential mobility was more important than any other social factor that we studied,” investigator David Alter, MD, PhD, chair of cardiovascular and metabolic research at the University Health Network–Toronto Rehabilitation Institute and associate professor of medicine at the University of Toronto, said in an interview.
The results were published online in the Canadian Journal of Cardiology.
Moving and mortality
“There’s been very little work, surprisingly, on what happens when individuals move from community to community,” said Dr. Alter. “It is that movement from community to community that is a factor within the social context that needs to be explored better. To the best of our knowledge, up until our study, it has been studied very briefly in the literature.”
The prospective cohort study sample included 3,369 patients who had an AMI between Dec. 1, 1999, and March 30, 2023. The investigators followed participants until death or the last available follow-up date of March 30, 2020. They defined a residential move as a relocation from one postal code region to another.
The investigators drew data from multiple sources, including the prospective, observational Socio-Economic Status and Acute Myocardial Infarction study, which encompassed more than 35,000 patient life-years following hospitalization for a first heart attack in Ontario. Mortality data were collected from the Ontario Registered Persons Data Base. Other sources included Statistics Canada for information on neighborhood income, the Canadian Institutes for Health Information for patients’ clinical factors and comorbidities, and the Ontario Health Insurance Plan (OHIP) database for physician visits. Information on long-term care admissions came from the Continuous Care Reporting System-Long Term Care, OHIP, and the Ontario Drugs Benefit databases, the latter of which also provided information on medication prescriptions for individuals aged 65 years and older.
Patients’ ages ranged from 19 to 101 years (median age, 65 years). About 69% of patients were men. Of the study population, 1,828 patients (54.3%) had at least one residential move during the study period. Approximately 87% died in the community or moved from home into a long-term care facility as an end-of-life destination. Overall, 84.8% of patients who were admitted to long-term care facilities died.
The study also tracked the socioeconomic status of persons living in the postal code regions from and to which patients moved. About 32% of patients moved to a neighborhood with a lower socioeconomic status, and 30.5% moved to an area with a higher socioeconomic status.
Each residential move was associated with a 12% higher rate of death and a 26% higher rate of long-term institutionalization for end-of-life care. In unadjusted analyses, the rate of death was almost double for those who moved more frequently: 44.3% for those who moved two or more times versus 24.8% for those who moved once in 10 years.
Accounting for a multitude of variables, such as the socioeconomic status of areas that patients moved between, is a strength of the study, said Dr. Alter. But the study lacked information about why people moved.
“Where this study has a huge amount of strength is that it was designed specifically to really understand a patient’s clinical and psychosocial profile at the start of their journey, their first AMI. But the fact that we took it from heart attack onward is also a strength because it characterizes and anchors a clinical context in which we were following patients out,” said Dr. Alter.
‘An important marker’
In a comment, Paul Oh, MD, medical director of the cardiovascular disease prevention and rehabilitation program at University Health Network, said: “This is a very well-designed study and analysis from a cohort that has provided important insights about the role of socioeconomic factors and long-term outcomes post MI over many years.” Dr. Oh did not participate in the study.
“A few covariates that could impact on outcomes, like institutionalization, were not available to include in adjusted analyses – e.g., functional status, frailty, mild cognitive changes, and availability of social supports in the home,” he said.
The findings add another variable that cardiologists who care for post-MI patients need to be aware of, Dr. Oh added. “Clinicians need better awareness that the need to change residence is an important marker of changing health status and may portend end-of-life events in the near future. The need to change residence can signal an important change in physical, cognitive, and social circumstances that needs to be further explored during clinical encounters, with the goal of identifying and addressing any potentially reversible issues and identifying additional supports that may help that individual continue to live independently in their own home.”
The study was supported by ICES, which receives funding from the Ontario Ministry of Health. The investigators disclosed no relevant financial relationships. Dr. Oh serves on research boards for Lilly and Novartis and receives research funding from Apple.
A version of this article first appeared on Medscape.com.
FROM THE CANADIAN JOURNAL OF CARDIOLOGY
AMA funds standardized BP training for medical, PA, and nursing schools
according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.
First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.
The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.
The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.
The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.
In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.
Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.
The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.
Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.
Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.
Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.
Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.
Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.
A version of this article first appeared on Medscape.com.
according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.
First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.
The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.
The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.
The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.
In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.
Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.
The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.
Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.
Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.
Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.
Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.
Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.
A version of this article first appeared on Medscape.com.
according to the American Medical Association. Hypertension affects about half of U.S. adults and is a leading contributor to cardiovascular disease.
First-year medical students typically read about BP measurement in a textbook and possibly attend a lecture before practicing using a manual cuff a few times on classmates, said Martha Gulati, MD, professor and director of preventive cardiology at Cedars-Sinai Medical Center, Los Angeles.
The dearth of BP instruction is alarming because inaccurate readings contribute to under- and overtreatment of hypertension, she said in an interview.
The AMA hopes $100,000 in grants to five health education schools will help improve BP instruction. The group recently announced it would give $20,000 each to five schools that train health professionals, expanding on a 2021 program to improve BP measurement training.
The new grants for interactive lessons will benefit nearly 5,000 students from Johns Hopkins University, Baltimore; Nova Southeastern University, Fort Lauderdale, Fla.; University of Washington, Seattle; Stony Brook (N.Y.) University; and the University of Pittsburgh.
In a 2021 survey of 571 clinicians, most of whom were cardiologists, Dr. Gulati found that only 23% performed accurate BP measurements despite the majority saying they trusted BP readings taken in their clinic. Accurate readings were defined as routinely checking BP in both arms, checking BP at least twice each visit, and waiting 5 minutes before taking the reading.
Med students fare no better when it comes to BP skills. In a 2017 study of 159 students from medical schools in 37 states, only one student demonstrated proficiency in all 11 elements necessary to measure BP accurately. Students, on average, performed just four of them correctly.
The elements of proper BP measurement include patients resting for 5 minutes before the measurement with legs uncrossed, feet on floor, and arm supported, not talking, reading, or using cell phone; BP taken in both arms with correct size of cuff placed over bare arm; and identifying BP from the arm with the higher reading as clinically more important and as the one to use for future readings.
Manual BP readings require an appropriately sized BP cuff, a sphygmomanometer, and a clinician skilled in using a stethoscope and auscultatory method. Meanwhile, automated readings require a clinician to place the cuff, but a digital device collects the measurement. Though preference depends on the setting and clinician, automated readings are more common. In Dr. Gulati’s study, automated BP assessment was used by 58% of respondents.
Depending on the BP device and technique, significant variations in readings can occur. In a 2021 study, Current Hypertension Reports found that automated readings may more closely reflect the patient’s baseline BP and produce results similar to ambulatory monitoring by a medical professional. An earlier JAMA Internal Medicine analysis found that clinicians’ manual readings reflect higher BP measurements than automated readings.
Though the AMA offers a free online series on BP measurement for students, making the training available to more health care team members can help prevent hypertension, said Kate Kirley, MD, director of the AMA’s chronic disease prevention and programs.
Concern over the lack of standardized BP techniques isn’t new. In 2019, the American Heart Association and the AMA created an online BP course for health care workers. Two years later, the AMA offered grants to five medical schools for training courses.
Most of the new training sessions already on the AMA website take students about 15 minutes to complete. Dr. Kirley says because equipment varies across settings, participants will learn how to conduct manual, semi-automated, and automated office BP readings and identify workarounds for less-than-ideal room setups that can skew results. They will also explore how to guide patients in performing BP readings at home.
A version of this article first appeared on Medscape.com.