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Takotsubo syndrome more deadly in men
Takotsubo syndrome occurs much more frequently in women than it does in men, but men are much more likely to die from it, according to the results of a new study.
In an analysis of almost 2,500 patients with Takotsubo syndrome (TSS) who were enrolled in an international registry, men, who made up just 11% of the sample, had significantly higher rates of cardiogenic shock and were more than twice as likely to die in the hospital than their female counterparts.
The authors concluded that TSS in males requires close in-hospital monitoring and long-term follow-up. Their study was published in the Journal of the American College of Cardiology.
Takotsubo syndrome is a condition characterized by acute heart failure and transient ventricular contractile dysfunction that can be precipitated by acute emotional or physical stress. It affects mostly women, particularly postmenopausal women, although the reasons for this are still not fully clear, Luca Arcari, MD, from the Institute of Cardiology, Madre Giuseppina Vannini Hospital, Rome, and colleagues wrote.
The syndrome also affects men, and recent data have identified that male sex is associated with worse outcomes. But, because it occurs relatively uncommonly in men, information about outcomes in men is limited.
To shed more light on the influence of gender on TTS, the investigators looked at 2,492 TTS patients (286 men, 2,206 women) who were participants in the GEIST (German Italian Spanish Takotsubo) registry and compared the clinical features and short- and long-term outcomes between the two.
Male patients were significantly younger (69 years) than women (71 years; P = .005) and had a higher prevalence of comorbid conditions, including diabetes (25% vs. 19%; P = .01); pulmonary diseases (21% vs. 15%; P = .006); malignancies (25% vs. 13%; P < .001).
In addition, TTS in men was more likely to be caused by physical triggers (55% vs. 32%; P < .01), whereas emotional triggers were more common in females (39% vs. 19%; P < 0.001).
The investigators then performed a propensity score analysis by matching men and women 1:1; this yielded 207 patients from each group.
After propensity matching, male patients had higher rates of cardiogenic shock (16% vs 6%), and in-hospital mortality (8% vs. 3%; both P < .05).
Men also had a higher mortality rate during the acute and long-term follow up. Male sex remained independently associated with both in-hospital mortality (odds ratio, 2.26; 95% confidence interval, 1.16-4.40) and long-term mortality (hazard ratio, 1.83; 95% CI, 1.32-2.52).
The study by Dr. Arcari and colleagues “shows convincingly that although men are far less likely to develop TTS than women, they have more serious complications and are more likely to die than women presenting with the syndrome, Ilan S. Wittstein, MD, of Johns Hopkins University, Baltimore, wrote in an accompanying editorial.
In an interview, Dr. Wittstein said one of the strengths of the study was its size.
“Over the years, there have been a lot of smaller, single center studies. This large registry had over 2,000 patients. So when the researchers say the rate of TTS is 10% in men and 90% in women, this is not necessarily surprising because that’s about the breakdown we’ve had since the very beginning, but it certainly validates that in a cohort that is large,” he said.
“I think what was novel about the paper is that the size of the cohort allowed the researchers to do propensity matching, so they were able not only to compare men versus women, they could do a 1:1 comparison. And they found even when you match men and women for various comorbidities, the men were much sicker
“What makes this a fascinating syndrome and different from most types of heart muscle problems is that, in the majority of patients, the condition is precipitated by an acute stressor,” said Dr. Wittstein.
“It can either be an emotional trigger, so for instance, getting some bad news that a loved one just died. That’s why we nicknamed the syndrome ‘broken heart syndrome’ many years ago. Or it can be a physical trigger, which can be a wide variety of things, such infection, a stroke, bad pneumonia, anything that stresses the body and causes a stress response. Regular heart attacks are not triggered in this way,” he said.
Dr. Arcari and Dr. Wittstein reported no relevant financial relationships.
Takotsubo syndrome occurs much more frequently in women than it does in men, but men are much more likely to die from it, according to the results of a new study.
In an analysis of almost 2,500 patients with Takotsubo syndrome (TSS) who were enrolled in an international registry, men, who made up just 11% of the sample, had significantly higher rates of cardiogenic shock and were more than twice as likely to die in the hospital than their female counterparts.
The authors concluded that TSS in males requires close in-hospital monitoring and long-term follow-up. Their study was published in the Journal of the American College of Cardiology.
Takotsubo syndrome is a condition characterized by acute heart failure and transient ventricular contractile dysfunction that can be precipitated by acute emotional or physical stress. It affects mostly women, particularly postmenopausal women, although the reasons for this are still not fully clear, Luca Arcari, MD, from the Institute of Cardiology, Madre Giuseppina Vannini Hospital, Rome, and colleagues wrote.
The syndrome also affects men, and recent data have identified that male sex is associated with worse outcomes. But, because it occurs relatively uncommonly in men, information about outcomes in men is limited.
To shed more light on the influence of gender on TTS, the investigators looked at 2,492 TTS patients (286 men, 2,206 women) who were participants in the GEIST (German Italian Spanish Takotsubo) registry and compared the clinical features and short- and long-term outcomes between the two.
Male patients were significantly younger (69 years) than women (71 years; P = .005) and had a higher prevalence of comorbid conditions, including diabetes (25% vs. 19%; P = .01); pulmonary diseases (21% vs. 15%; P = .006); malignancies (25% vs. 13%; P < .001).
In addition, TTS in men was more likely to be caused by physical triggers (55% vs. 32%; P < .01), whereas emotional triggers were more common in females (39% vs. 19%; P < 0.001).
The investigators then performed a propensity score analysis by matching men and women 1:1; this yielded 207 patients from each group.
After propensity matching, male patients had higher rates of cardiogenic shock (16% vs 6%), and in-hospital mortality (8% vs. 3%; both P < .05).
Men also had a higher mortality rate during the acute and long-term follow up. Male sex remained independently associated with both in-hospital mortality (odds ratio, 2.26; 95% confidence interval, 1.16-4.40) and long-term mortality (hazard ratio, 1.83; 95% CI, 1.32-2.52).
The study by Dr. Arcari and colleagues “shows convincingly that although men are far less likely to develop TTS than women, they have more serious complications and are more likely to die than women presenting with the syndrome, Ilan S. Wittstein, MD, of Johns Hopkins University, Baltimore, wrote in an accompanying editorial.
In an interview, Dr. Wittstein said one of the strengths of the study was its size.
“Over the years, there have been a lot of smaller, single center studies. This large registry had over 2,000 patients. So when the researchers say the rate of TTS is 10% in men and 90% in women, this is not necessarily surprising because that’s about the breakdown we’ve had since the very beginning, but it certainly validates that in a cohort that is large,” he said.
“I think what was novel about the paper is that the size of the cohort allowed the researchers to do propensity matching, so they were able not only to compare men versus women, they could do a 1:1 comparison. And they found even when you match men and women for various comorbidities, the men were much sicker
“What makes this a fascinating syndrome and different from most types of heart muscle problems is that, in the majority of patients, the condition is precipitated by an acute stressor,” said Dr. Wittstein.
“It can either be an emotional trigger, so for instance, getting some bad news that a loved one just died. That’s why we nicknamed the syndrome ‘broken heart syndrome’ many years ago. Or it can be a physical trigger, which can be a wide variety of things, such infection, a stroke, bad pneumonia, anything that stresses the body and causes a stress response. Regular heart attacks are not triggered in this way,” he said.
Dr. Arcari and Dr. Wittstein reported no relevant financial relationships.
Takotsubo syndrome occurs much more frequently in women than it does in men, but men are much more likely to die from it, according to the results of a new study.
In an analysis of almost 2,500 patients with Takotsubo syndrome (TSS) who were enrolled in an international registry, men, who made up just 11% of the sample, had significantly higher rates of cardiogenic shock and were more than twice as likely to die in the hospital than their female counterparts.
The authors concluded that TSS in males requires close in-hospital monitoring and long-term follow-up. Their study was published in the Journal of the American College of Cardiology.
Takotsubo syndrome is a condition characterized by acute heart failure and transient ventricular contractile dysfunction that can be precipitated by acute emotional or physical stress. It affects mostly women, particularly postmenopausal women, although the reasons for this are still not fully clear, Luca Arcari, MD, from the Institute of Cardiology, Madre Giuseppina Vannini Hospital, Rome, and colleagues wrote.
The syndrome also affects men, and recent data have identified that male sex is associated with worse outcomes. But, because it occurs relatively uncommonly in men, information about outcomes in men is limited.
To shed more light on the influence of gender on TTS, the investigators looked at 2,492 TTS patients (286 men, 2,206 women) who were participants in the GEIST (German Italian Spanish Takotsubo) registry and compared the clinical features and short- and long-term outcomes between the two.
Male patients were significantly younger (69 years) than women (71 years; P = .005) and had a higher prevalence of comorbid conditions, including diabetes (25% vs. 19%; P = .01); pulmonary diseases (21% vs. 15%; P = .006); malignancies (25% vs. 13%; P < .001).
In addition, TTS in men was more likely to be caused by physical triggers (55% vs. 32%; P < .01), whereas emotional triggers were more common in females (39% vs. 19%; P < 0.001).
The investigators then performed a propensity score analysis by matching men and women 1:1; this yielded 207 patients from each group.
After propensity matching, male patients had higher rates of cardiogenic shock (16% vs 6%), and in-hospital mortality (8% vs. 3%; both P < .05).
Men also had a higher mortality rate during the acute and long-term follow up. Male sex remained independently associated with both in-hospital mortality (odds ratio, 2.26; 95% confidence interval, 1.16-4.40) and long-term mortality (hazard ratio, 1.83; 95% CI, 1.32-2.52).
The study by Dr. Arcari and colleagues “shows convincingly that although men are far less likely to develop TTS than women, they have more serious complications and are more likely to die than women presenting with the syndrome, Ilan S. Wittstein, MD, of Johns Hopkins University, Baltimore, wrote in an accompanying editorial.
In an interview, Dr. Wittstein said one of the strengths of the study was its size.
“Over the years, there have been a lot of smaller, single center studies. This large registry had over 2,000 patients. So when the researchers say the rate of TTS is 10% in men and 90% in women, this is not necessarily surprising because that’s about the breakdown we’ve had since the very beginning, but it certainly validates that in a cohort that is large,” he said.
“I think what was novel about the paper is that the size of the cohort allowed the researchers to do propensity matching, so they were able not only to compare men versus women, they could do a 1:1 comparison. And they found even when you match men and women for various comorbidities, the men were much sicker
“What makes this a fascinating syndrome and different from most types of heart muscle problems is that, in the majority of patients, the condition is precipitated by an acute stressor,” said Dr. Wittstein.
“It can either be an emotional trigger, so for instance, getting some bad news that a loved one just died. That’s why we nicknamed the syndrome ‘broken heart syndrome’ many years ago. Or it can be a physical trigger, which can be a wide variety of things, such infection, a stroke, bad pneumonia, anything that stresses the body and causes a stress response. Regular heart attacks are not triggered in this way,” he said.
Dr. Arcari and Dr. Wittstein reported no relevant financial relationships.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Polypharmacy common among patients aged 65 or older with HIV
People aged 65 or older with human immunodeficiency virus (HIV) receive significantly more nonantiretroviral therapy (non-ART) medications, compared with patients with HIV who are between ages 50 and 64, according to a new study.
Moreover, in a sample of more than 900 patients with HIV, about 60% were taking at least one potentially inappropriate medication (PIM).
“Clinicians looking after persons living with HIV need to provide medication reconciliation with prioritization of medications based on the patients’ wishes and patients’ goals and life expectancy,” lead author Jacqueline McMillan, MD, clinical assistant professor of geriatric medicine at the University of Calgary (Alt.) told this news organization.
The findings were published online in the Canadian Journal of General Internal Medicine.
Examining the pill burden
A geriatrician by training and a clinical researcher with an interest in aging in patients with HIV, Dr. McMillan said she began to observe that many older adults with HIV were on polypharmacy. “There are many other things that aging people with HIV experience, such as frailty, falls, cognitive impairment, medication nonadherence, and mortality, but in this study, we focused just on the polypharmacy,” said Dr. McMillan.
Her aim was to see if there was a way to improve the pill burden in these older adults.
“Do they need to be on all of these medications? Is there anything that we were overprescribing that they no longer needed, or possibly not prescribing and undertreating people because they were older? I wanted to have a better sense that the medications we were prescribing were appropriate and that we minimized the pill burden for older adults,” Dr. McMillan said.
Persons with HIV are at a particularly increased risk of polypharmacy and potential drug-drug interactions because they need antiretroviral therapy medications and medications to treat comorbidities.
“Certainly, when the ARTs were first discovered, sometimes that regimen required several pills a day, but as time has gone on and our retrovirals have gotten better, some of those requirements have narrowed down to one-pill-a-day regimens. We are now replacing that pill burden with non-HIV drugs,” said Dr. McMillan.
The researchers obtained medication reconciliation data for 951 persons with HIV aged 50 or older as of Feb. 1, 2020. The study population was receiving HIV care through the Southern Alberta HIV Clinic in Calgary. The researchers defined polypharmacy as taking five or more non-ART drugs. They defined PIMs according to the 2019 Beers criteria.
In their analysis, the researchers compared patients aged 65 or older with patients aged 50-64, as well as patients with shorter (< 10 years) and longer (> 10 years) duration of HIV infection.
PIM use common
The population’s mean age was 59 years, and 82% were men. The mean time since HIV diagnosis was 17.8 years, and the median time was 17 years. Most (80%) of the patients were aged 50-64 years, and 20% were 65 and older.
The researchers collected sociodemographic, clinical, medication, and laboratory data for all patients at each clinical visit.
The mean number of non-ART medications was 6.7 for the population. Patients aged 65 years or older were taking significantly more non-ART medications than patients aged 50-64 (8.4 vs. 6.3; P < .001).
Similarly, those living with HIV for more than 10 years were taking significantly more non-ART medications (mean, 6.9) than those living with HIV for 10 or fewer years (mean 6.1; P = .0168).
In all, almost 60% of patients were taking at least one PIM. The mean number of PIMs per patient was 1.6.
Patients living with diagnosed HIV infection for more than 10 years were at greater risk of PIMs (1.6 PIMs) than those with shorter duration of HIV diagnosis (1.4 PIMs; P = .06).
Dr. McMillan says she hopes her study reminds clinicians to review patients’ medications at each visit and ensure they are neither over- nor underprescribing.
“From my perspective as a geriatrician, I hope that we do more dedicated medication reconciliation to actually make sure we know what people are taking,” she said. She asks patients to bring all their medications to the office so that they can review which ones match their diagnoses.
“I want to do more patient-centered personalized care for older adults, with a focus on people who are frail and who may have a limited life expectancy, so that we don’t have someone with a short life expectancy still taking 15 medications a day,” said Dr. McMillan.
‘Carefully document medications’
“This study identifies potentially inappropriate medication use in a group of older people living with HIV who are particularly vulnerable to it at an earlier age because of their medical complexity or frailty than perhaps healthy older adults,” Adrian Wagg, MD, professor of healthy aging in the department of medicine at the University of Alberta, Edmonton, told this news organization.
The study emphasizes the importance of careful documentation of medications that the patient is taking at every clinical visit, he said.
“Make sure you carefully document medications which are taken whenever you see the individual. Also try to limit the number of prescribers, because we know multiple prescribers are associated with greater likelihood of inappropriate prescribing,” Dr. Wagg said.
The move to wean patients from inappropriate medications is gaining momentum, he added.
“There is a huge movement now around actively deprescribing medications which are either no longer indicated or potentially of little benefit, given remaining life expectancy,” said Dr. Wagg. Drugs such as proton pump inhibitors, hypnotics, unrequired antidepressants, and benzodiazepines are the first targets for elimination, he concluded.
The study was funded by the University of Calgary. Dr. McMillan and Dr. Wagg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People aged 65 or older with human immunodeficiency virus (HIV) receive significantly more nonantiretroviral therapy (non-ART) medications, compared with patients with HIV who are between ages 50 and 64, according to a new study.
Moreover, in a sample of more than 900 patients with HIV, about 60% were taking at least one potentially inappropriate medication (PIM).
“Clinicians looking after persons living with HIV need to provide medication reconciliation with prioritization of medications based on the patients’ wishes and patients’ goals and life expectancy,” lead author Jacqueline McMillan, MD, clinical assistant professor of geriatric medicine at the University of Calgary (Alt.) told this news organization.
The findings were published online in the Canadian Journal of General Internal Medicine.
Examining the pill burden
A geriatrician by training and a clinical researcher with an interest in aging in patients with HIV, Dr. McMillan said she began to observe that many older adults with HIV were on polypharmacy. “There are many other things that aging people with HIV experience, such as frailty, falls, cognitive impairment, medication nonadherence, and mortality, but in this study, we focused just on the polypharmacy,” said Dr. McMillan.
Her aim was to see if there was a way to improve the pill burden in these older adults.
“Do they need to be on all of these medications? Is there anything that we were overprescribing that they no longer needed, or possibly not prescribing and undertreating people because they were older? I wanted to have a better sense that the medications we were prescribing were appropriate and that we minimized the pill burden for older adults,” Dr. McMillan said.
Persons with HIV are at a particularly increased risk of polypharmacy and potential drug-drug interactions because they need antiretroviral therapy medications and medications to treat comorbidities.
“Certainly, when the ARTs were first discovered, sometimes that regimen required several pills a day, but as time has gone on and our retrovirals have gotten better, some of those requirements have narrowed down to one-pill-a-day regimens. We are now replacing that pill burden with non-HIV drugs,” said Dr. McMillan.
The researchers obtained medication reconciliation data for 951 persons with HIV aged 50 or older as of Feb. 1, 2020. The study population was receiving HIV care through the Southern Alberta HIV Clinic in Calgary. The researchers defined polypharmacy as taking five or more non-ART drugs. They defined PIMs according to the 2019 Beers criteria.
In their analysis, the researchers compared patients aged 65 or older with patients aged 50-64, as well as patients with shorter (< 10 years) and longer (> 10 years) duration of HIV infection.
PIM use common
The population’s mean age was 59 years, and 82% were men. The mean time since HIV diagnosis was 17.8 years, and the median time was 17 years. Most (80%) of the patients were aged 50-64 years, and 20% were 65 and older.
The researchers collected sociodemographic, clinical, medication, and laboratory data for all patients at each clinical visit.
The mean number of non-ART medications was 6.7 for the population. Patients aged 65 years or older were taking significantly more non-ART medications than patients aged 50-64 (8.4 vs. 6.3; P < .001).
Similarly, those living with HIV for more than 10 years were taking significantly more non-ART medications (mean, 6.9) than those living with HIV for 10 or fewer years (mean 6.1; P = .0168).
In all, almost 60% of patients were taking at least one PIM. The mean number of PIMs per patient was 1.6.
Patients living with diagnosed HIV infection for more than 10 years were at greater risk of PIMs (1.6 PIMs) than those with shorter duration of HIV diagnosis (1.4 PIMs; P = .06).
Dr. McMillan says she hopes her study reminds clinicians to review patients’ medications at each visit and ensure they are neither over- nor underprescribing.
“From my perspective as a geriatrician, I hope that we do more dedicated medication reconciliation to actually make sure we know what people are taking,” she said. She asks patients to bring all their medications to the office so that they can review which ones match their diagnoses.
“I want to do more patient-centered personalized care for older adults, with a focus on people who are frail and who may have a limited life expectancy, so that we don’t have someone with a short life expectancy still taking 15 medications a day,” said Dr. McMillan.
‘Carefully document medications’
“This study identifies potentially inappropriate medication use in a group of older people living with HIV who are particularly vulnerable to it at an earlier age because of their medical complexity or frailty than perhaps healthy older adults,” Adrian Wagg, MD, professor of healthy aging in the department of medicine at the University of Alberta, Edmonton, told this news organization.
The study emphasizes the importance of careful documentation of medications that the patient is taking at every clinical visit, he said.
“Make sure you carefully document medications which are taken whenever you see the individual. Also try to limit the number of prescribers, because we know multiple prescribers are associated with greater likelihood of inappropriate prescribing,” Dr. Wagg said.
The move to wean patients from inappropriate medications is gaining momentum, he added.
“There is a huge movement now around actively deprescribing medications which are either no longer indicated or potentially of little benefit, given remaining life expectancy,” said Dr. Wagg. Drugs such as proton pump inhibitors, hypnotics, unrequired antidepressants, and benzodiazepines are the first targets for elimination, he concluded.
The study was funded by the University of Calgary. Dr. McMillan and Dr. Wagg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
People aged 65 or older with human immunodeficiency virus (HIV) receive significantly more nonantiretroviral therapy (non-ART) medications, compared with patients with HIV who are between ages 50 and 64, according to a new study.
Moreover, in a sample of more than 900 patients with HIV, about 60% were taking at least one potentially inappropriate medication (PIM).
“Clinicians looking after persons living with HIV need to provide medication reconciliation with prioritization of medications based on the patients’ wishes and patients’ goals and life expectancy,” lead author Jacqueline McMillan, MD, clinical assistant professor of geriatric medicine at the University of Calgary (Alt.) told this news organization.
The findings were published online in the Canadian Journal of General Internal Medicine.
Examining the pill burden
A geriatrician by training and a clinical researcher with an interest in aging in patients with HIV, Dr. McMillan said she began to observe that many older adults with HIV were on polypharmacy. “There are many other things that aging people with HIV experience, such as frailty, falls, cognitive impairment, medication nonadherence, and mortality, but in this study, we focused just on the polypharmacy,” said Dr. McMillan.
Her aim was to see if there was a way to improve the pill burden in these older adults.
“Do they need to be on all of these medications? Is there anything that we were overprescribing that they no longer needed, or possibly not prescribing and undertreating people because they were older? I wanted to have a better sense that the medications we were prescribing were appropriate and that we minimized the pill burden for older adults,” Dr. McMillan said.
Persons with HIV are at a particularly increased risk of polypharmacy and potential drug-drug interactions because they need antiretroviral therapy medications and medications to treat comorbidities.
“Certainly, when the ARTs were first discovered, sometimes that regimen required several pills a day, but as time has gone on and our retrovirals have gotten better, some of those requirements have narrowed down to one-pill-a-day regimens. We are now replacing that pill burden with non-HIV drugs,” said Dr. McMillan.
The researchers obtained medication reconciliation data for 951 persons with HIV aged 50 or older as of Feb. 1, 2020. The study population was receiving HIV care through the Southern Alberta HIV Clinic in Calgary. The researchers defined polypharmacy as taking five or more non-ART drugs. They defined PIMs according to the 2019 Beers criteria.
In their analysis, the researchers compared patients aged 65 or older with patients aged 50-64, as well as patients with shorter (< 10 years) and longer (> 10 years) duration of HIV infection.
PIM use common
The population’s mean age was 59 years, and 82% were men. The mean time since HIV diagnosis was 17.8 years, and the median time was 17 years. Most (80%) of the patients were aged 50-64 years, and 20% were 65 and older.
The researchers collected sociodemographic, clinical, medication, and laboratory data for all patients at each clinical visit.
The mean number of non-ART medications was 6.7 for the population. Patients aged 65 years or older were taking significantly more non-ART medications than patients aged 50-64 (8.4 vs. 6.3; P < .001).
Similarly, those living with HIV for more than 10 years were taking significantly more non-ART medications (mean, 6.9) than those living with HIV for 10 or fewer years (mean 6.1; P = .0168).
In all, almost 60% of patients were taking at least one PIM. The mean number of PIMs per patient was 1.6.
Patients living with diagnosed HIV infection for more than 10 years were at greater risk of PIMs (1.6 PIMs) than those with shorter duration of HIV diagnosis (1.4 PIMs; P = .06).
Dr. McMillan says she hopes her study reminds clinicians to review patients’ medications at each visit and ensure they are neither over- nor underprescribing.
“From my perspective as a geriatrician, I hope that we do more dedicated medication reconciliation to actually make sure we know what people are taking,” she said. She asks patients to bring all their medications to the office so that they can review which ones match their diagnoses.
“I want to do more patient-centered personalized care for older adults, with a focus on people who are frail and who may have a limited life expectancy, so that we don’t have someone with a short life expectancy still taking 15 medications a day,” said Dr. McMillan.
‘Carefully document medications’
“This study identifies potentially inappropriate medication use in a group of older people living with HIV who are particularly vulnerable to it at an earlier age because of their medical complexity or frailty than perhaps healthy older adults,” Adrian Wagg, MD, professor of healthy aging in the department of medicine at the University of Alberta, Edmonton, told this news organization.
The study emphasizes the importance of careful documentation of medications that the patient is taking at every clinical visit, he said.
“Make sure you carefully document medications which are taken whenever you see the individual. Also try to limit the number of prescribers, because we know multiple prescribers are associated with greater likelihood of inappropriate prescribing,” Dr. Wagg said.
The move to wean patients from inappropriate medications is gaining momentum, he added.
“There is a huge movement now around actively deprescribing medications which are either no longer indicated or potentially of little benefit, given remaining life expectancy,” said Dr. Wagg. Drugs such as proton pump inhibitors, hypnotics, unrequired antidepressants, and benzodiazepines are the first targets for elimination, he concluded.
The study was funded by the University of Calgary. Dr. McMillan and Dr. Wagg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE CANADIAN JOURNAL OF GENERAL INTERNAL MEDICINE
The best statins to lower non-HDL cholesterol in diabetes?
A network meta-analysis of 42 clinical trials concludes that rosuvastatin, simvastatin, and atorvastatin are the statins most effective at lowering non-high-density-lipoprotein cholesterol (non-HDL-C) in people with diabetes and at risk for cardiovascular disease.
The analysis focused on the efficacy of statin treatment on reducing non-HDL-C, as opposed to reducing low-density-lipoprotein cholesterol (LDL-C), which has traditionally been used as a surrogate to determine cardiovascular disease risk from hypercholesterolemia.
“The National Cholesterol Education Program in the United States recommends that LDL-C values should be used to estimate the risk of cardiovascular disease related to lipoproteins,” lead author Alexander Hodkinson, MD, senior National Institute for Health Research fellow, University of Manchester, England, told this news organization.
“But we believe that non-high-density-lipoprotein cholesterol is more strongly associated with the risk of cardiovascular disease, because non-HDL-C combines all the bad types of cholesterol, which LDL-C misses, so it could be a better tool than LDL-C for assessing CVD risk and effects of treatment. We already knew which of the statins reduce LDL-C, but we wanted to know which ones reduced non-HDL-C; hence the reason for our study,” Dr. Hodkinson said.
The findings were published online in BMJ.
In April 2021, the National Institute for Health and Care Excellence (NICE) in the United Kingdom updated guidelines for adults with diabetes to recommend that non-HDL-C should replace LDL-C as the primary target for reducing the risk for cardiovascular disease with lipid-lowering treatment.
Currently, NICE is alone in its recommendation. Other international guidelines do not have a non-HDL-C target and use LDL-C reduction instead. These include guidelines from the European Society of Cardiology (ESC), the American College of Cardiology (ACC), the American Heart Association (AHA), and the National Lipid Association.
Non–HDL-C is simple to calculate and can easily be done by clinicians by subtracting HDL-C from the total cholesterol level, he added.
This analysis compared the effectiveness of different statins at different intensities in reducing levels of non-HDL-C in 42 randomized controlled trials that included 20,193 adults with diabetes.
Compared with placebo, rosuvastatin, given at moderate- and high-intensity doses, and simvastatin and atorvastatin at high-intensity doses, were the best at lowering levels of non-HDL-C over an average treatment period of 12 weeks.
High-intensity rosuvastatin led to a 2.31 mmol/L reduction in non-HDL-C (95% credible interval, –3.39 to –1.21). Moderate-intensity rosuvastatin led to a 2.27 mmol/L reduction in non-HDL-C (95% credible interval, –3.00 to –1.49).
High-intensity simvastatin led to a 2.26 mmol/L reduction in non-HDL-C (95% credible interval, –2.99 to –1.51).
High-intensity atorvastatin led to a 2.20 mmol/L reduction in non-HDL-C (95% credible interval, –2.69 to –1.70).
Atorvastatin and simvastatin at any intensity and pravastatin at low intensity were also effective in reducing levels of non-HDL-C, the researchers noted.
In 4,670 patients who were at great risk for a major cardiovascular event, atorvastatin at high intensity showed the largest reduction in levels of non-HDL-C (1.98 mmol/L; 95% credible interval, –4.16 to 0.26).
In addition, high-intensity simvastatin and rosuvastatin were the most effective in reducing LDL-C.
High-intensity simvastatin led to a 1.93 mmol/L reduction in LDL-C (95% credible interval, –2.63 to –1.21), and high-intensity rosuvastatin led to a 1.76 mmol/L reduction in LDL-C (95% credible interval, –2.37 to –1.15).
In four studies, significant reductions in nonfatal myocardial infarction were shown for atorvastatin at moderate intensity, compared with placebo (relative risk, 0.57; 95% confidence interval, 0.43-.76). No significant differences were seen for discontinuations, nonfatal stroke, or cardiovascular death.
“We hope our findings will help guide clinicians on statin selection itself, and what types of doses they should be giving patients. These results support using NICE’s new policy guidelines on cholesterol monitoring, using this non-HDL-C measure, which contains all the bad types of cholesterol for patients with diabetes,” Dr. Hodkinson said.
“This study further emphasizes what we have known about the benefit of statin therapy in patients with type 2 diabetes,” Prakash Deedwania, MD, professor of medicine, University of California, San Francisco, told this news organization.
Dr. Deedwania and others have published data on patients with diabetes that showed that treatment with high-intensity atorvastatin was associated with significant reductions in major adverse cardiovascular events.
“Here they use non-HDL cholesterol as a target. The NICE guidelines are the only guidelines looking at non-HDL cholesterol; however, all guidelines suggest an LDL to be less than 70 in all people with diabetes, and for those with recent acute coronary syndromes, the latest evidence suggests the LDL should actually be less than 50,” said Dr. Deedwania, spokesperson for the AHA and ACC.
As far as which measure to use, he believes both are useful. “It’s six of one and half a dozen of the other, in my opinion. The societies have not recommended non-HDL cholesterol and it’s easier to stay with what is readily available for clinicians, and using LDL cholesterol is still okay. The results of this analysis are confirmatory, in that looking at non-HDL cholesterol gives results very similar to what these statins have shown for their effect on LDL cholesterol,” he said.
Non-HDL cholesterol a better marker?
For Robert Rosenson, MD, director of metabolism and lipids at Mount Sinai Health System and professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai, New York, non-HDL cholesterol is becoming an important marker of risk for several reasons.
“The focus on LDL cholesterol has been due to the causal relationship of LDL with atherosclerotic cardiovascular disease, but in the last few decades, non-HDL has emerged because more people are overweight, have insulin resistance, and have diabetes,” Dr. Rosenson told this news organization. “In those situations, the LDL cholesterol underrepresents the risk of the LDL particles. With insulin resistance, the particles become more triglycerides and less cholesterol, so on a per-particle basis, you need to get more LDL particles to get to a certain LDL cholesterol concentration.”
Non-HDL cholesterol testing does not require fasting, another advantage of using it to monitor cholesterol, he added.
What is often forgotten is that moderate- to high-intensity statins have very good triglyceride-lowering effects, Dr. Rosenson said.
“This article highlights that, by using higher doses, you get more triglyceride-lowering. Hopefully, this will get practitioners to recognize that non-HDL cholesterol is a better predictor of risk in people with diabetes,” he said.
The study was funded by the National Institute for Health Research. Dr. Hodkinson, Dr. Rosenson, and Dr. Deedwania report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A network meta-analysis of 42 clinical trials concludes that rosuvastatin, simvastatin, and atorvastatin are the statins most effective at lowering non-high-density-lipoprotein cholesterol (non-HDL-C) in people with diabetes and at risk for cardiovascular disease.
The analysis focused on the efficacy of statin treatment on reducing non-HDL-C, as opposed to reducing low-density-lipoprotein cholesterol (LDL-C), which has traditionally been used as a surrogate to determine cardiovascular disease risk from hypercholesterolemia.
“The National Cholesterol Education Program in the United States recommends that LDL-C values should be used to estimate the risk of cardiovascular disease related to lipoproteins,” lead author Alexander Hodkinson, MD, senior National Institute for Health Research fellow, University of Manchester, England, told this news organization.
“But we believe that non-high-density-lipoprotein cholesterol is more strongly associated with the risk of cardiovascular disease, because non-HDL-C combines all the bad types of cholesterol, which LDL-C misses, so it could be a better tool than LDL-C for assessing CVD risk and effects of treatment. We already knew which of the statins reduce LDL-C, but we wanted to know which ones reduced non-HDL-C; hence the reason for our study,” Dr. Hodkinson said.
The findings were published online in BMJ.
In April 2021, the National Institute for Health and Care Excellence (NICE) in the United Kingdom updated guidelines for adults with diabetes to recommend that non-HDL-C should replace LDL-C as the primary target for reducing the risk for cardiovascular disease with lipid-lowering treatment.
Currently, NICE is alone in its recommendation. Other international guidelines do not have a non-HDL-C target and use LDL-C reduction instead. These include guidelines from the European Society of Cardiology (ESC), the American College of Cardiology (ACC), the American Heart Association (AHA), and the National Lipid Association.
Non–HDL-C is simple to calculate and can easily be done by clinicians by subtracting HDL-C from the total cholesterol level, he added.
This analysis compared the effectiveness of different statins at different intensities in reducing levels of non-HDL-C in 42 randomized controlled trials that included 20,193 adults with diabetes.
Compared with placebo, rosuvastatin, given at moderate- and high-intensity doses, and simvastatin and atorvastatin at high-intensity doses, were the best at lowering levels of non-HDL-C over an average treatment period of 12 weeks.
High-intensity rosuvastatin led to a 2.31 mmol/L reduction in non-HDL-C (95% credible interval, –3.39 to –1.21). Moderate-intensity rosuvastatin led to a 2.27 mmol/L reduction in non-HDL-C (95% credible interval, –3.00 to –1.49).
High-intensity simvastatin led to a 2.26 mmol/L reduction in non-HDL-C (95% credible interval, –2.99 to –1.51).
High-intensity atorvastatin led to a 2.20 mmol/L reduction in non-HDL-C (95% credible interval, –2.69 to –1.70).
Atorvastatin and simvastatin at any intensity and pravastatin at low intensity were also effective in reducing levels of non-HDL-C, the researchers noted.
In 4,670 patients who were at great risk for a major cardiovascular event, atorvastatin at high intensity showed the largest reduction in levels of non-HDL-C (1.98 mmol/L; 95% credible interval, –4.16 to 0.26).
In addition, high-intensity simvastatin and rosuvastatin were the most effective in reducing LDL-C.
High-intensity simvastatin led to a 1.93 mmol/L reduction in LDL-C (95% credible interval, –2.63 to –1.21), and high-intensity rosuvastatin led to a 1.76 mmol/L reduction in LDL-C (95% credible interval, –2.37 to –1.15).
In four studies, significant reductions in nonfatal myocardial infarction were shown for atorvastatin at moderate intensity, compared with placebo (relative risk, 0.57; 95% confidence interval, 0.43-.76). No significant differences were seen for discontinuations, nonfatal stroke, or cardiovascular death.
“We hope our findings will help guide clinicians on statin selection itself, and what types of doses they should be giving patients. These results support using NICE’s new policy guidelines on cholesterol monitoring, using this non-HDL-C measure, which contains all the bad types of cholesterol for patients with diabetes,” Dr. Hodkinson said.
“This study further emphasizes what we have known about the benefit of statin therapy in patients with type 2 diabetes,” Prakash Deedwania, MD, professor of medicine, University of California, San Francisco, told this news organization.
Dr. Deedwania and others have published data on patients with diabetes that showed that treatment with high-intensity atorvastatin was associated with significant reductions in major adverse cardiovascular events.
“Here they use non-HDL cholesterol as a target. The NICE guidelines are the only guidelines looking at non-HDL cholesterol; however, all guidelines suggest an LDL to be less than 70 in all people with diabetes, and for those with recent acute coronary syndromes, the latest evidence suggests the LDL should actually be less than 50,” said Dr. Deedwania, spokesperson for the AHA and ACC.
As far as which measure to use, he believes both are useful. “It’s six of one and half a dozen of the other, in my opinion. The societies have not recommended non-HDL cholesterol and it’s easier to stay with what is readily available for clinicians, and using LDL cholesterol is still okay. The results of this analysis are confirmatory, in that looking at non-HDL cholesterol gives results very similar to what these statins have shown for their effect on LDL cholesterol,” he said.
Non-HDL cholesterol a better marker?
For Robert Rosenson, MD, director of metabolism and lipids at Mount Sinai Health System and professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai, New York, non-HDL cholesterol is becoming an important marker of risk for several reasons.
“The focus on LDL cholesterol has been due to the causal relationship of LDL with atherosclerotic cardiovascular disease, but in the last few decades, non-HDL has emerged because more people are overweight, have insulin resistance, and have diabetes,” Dr. Rosenson told this news organization. “In those situations, the LDL cholesterol underrepresents the risk of the LDL particles. With insulin resistance, the particles become more triglycerides and less cholesterol, so on a per-particle basis, you need to get more LDL particles to get to a certain LDL cholesterol concentration.”
Non-HDL cholesterol testing does not require fasting, another advantage of using it to monitor cholesterol, he added.
What is often forgotten is that moderate- to high-intensity statins have very good triglyceride-lowering effects, Dr. Rosenson said.
“This article highlights that, by using higher doses, you get more triglyceride-lowering. Hopefully, this will get practitioners to recognize that non-HDL cholesterol is a better predictor of risk in people with diabetes,” he said.
The study was funded by the National Institute for Health Research. Dr. Hodkinson, Dr. Rosenson, and Dr. Deedwania report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A network meta-analysis of 42 clinical trials concludes that rosuvastatin, simvastatin, and atorvastatin are the statins most effective at lowering non-high-density-lipoprotein cholesterol (non-HDL-C) in people with diabetes and at risk for cardiovascular disease.
The analysis focused on the efficacy of statin treatment on reducing non-HDL-C, as opposed to reducing low-density-lipoprotein cholesterol (LDL-C), which has traditionally been used as a surrogate to determine cardiovascular disease risk from hypercholesterolemia.
“The National Cholesterol Education Program in the United States recommends that LDL-C values should be used to estimate the risk of cardiovascular disease related to lipoproteins,” lead author Alexander Hodkinson, MD, senior National Institute for Health Research fellow, University of Manchester, England, told this news organization.
“But we believe that non-high-density-lipoprotein cholesterol is more strongly associated with the risk of cardiovascular disease, because non-HDL-C combines all the bad types of cholesterol, which LDL-C misses, so it could be a better tool than LDL-C for assessing CVD risk and effects of treatment. We already knew which of the statins reduce LDL-C, but we wanted to know which ones reduced non-HDL-C; hence the reason for our study,” Dr. Hodkinson said.
The findings were published online in BMJ.
In April 2021, the National Institute for Health and Care Excellence (NICE) in the United Kingdom updated guidelines for adults with diabetes to recommend that non-HDL-C should replace LDL-C as the primary target for reducing the risk for cardiovascular disease with lipid-lowering treatment.
Currently, NICE is alone in its recommendation. Other international guidelines do not have a non-HDL-C target and use LDL-C reduction instead. These include guidelines from the European Society of Cardiology (ESC), the American College of Cardiology (ACC), the American Heart Association (AHA), and the National Lipid Association.
Non–HDL-C is simple to calculate and can easily be done by clinicians by subtracting HDL-C from the total cholesterol level, he added.
This analysis compared the effectiveness of different statins at different intensities in reducing levels of non-HDL-C in 42 randomized controlled trials that included 20,193 adults with diabetes.
Compared with placebo, rosuvastatin, given at moderate- and high-intensity doses, and simvastatin and atorvastatin at high-intensity doses, were the best at lowering levels of non-HDL-C over an average treatment period of 12 weeks.
High-intensity rosuvastatin led to a 2.31 mmol/L reduction in non-HDL-C (95% credible interval, –3.39 to –1.21). Moderate-intensity rosuvastatin led to a 2.27 mmol/L reduction in non-HDL-C (95% credible interval, –3.00 to –1.49).
High-intensity simvastatin led to a 2.26 mmol/L reduction in non-HDL-C (95% credible interval, –2.99 to –1.51).
High-intensity atorvastatin led to a 2.20 mmol/L reduction in non-HDL-C (95% credible interval, –2.69 to –1.70).
Atorvastatin and simvastatin at any intensity and pravastatin at low intensity were also effective in reducing levels of non-HDL-C, the researchers noted.
In 4,670 patients who were at great risk for a major cardiovascular event, atorvastatin at high intensity showed the largest reduction in levels of non-HDL-C (1.98 mmol/L; 95% credible interval, –4.16 to 0.26).
In addition, high-intensity simvastatin and rosuvastatin were the most effective in reducing LDL-C.
High-intensity simvastatin led to a 1.93 mmol/L reduction in LDL-C (95% credible interval, –2.63 to –1.21), and high-intensity rosuvastatin led to a 1.76 mmol/L reduction in LDL-C (95% credible interval, –2.37 to –1.15).
In four studies, significant reductions in nonfatal myocardial infarction were shown for atorvastatin at moderate intensity, compared with placebo (relative risk, 0.57; 95% confidence interval, 0.43-.76). No significant differences were seen for discontinuations, nonfatal stroke, or cardiovascular death.
“We hope our findings will help guide clinicians on statin selection itself, and what types of doses they should be giving patients. These results support using NICE’s new policy guidelines on cholesterol monitoring, using this non-HDL-C measure, which contains all the bad types of cholesterol for patients with diabetes,” Dr. Hodkinson said.
“This study further emphasizes what we have known about the benefit of statin therapy in patients with type 2 diabetes,” Prakash Deedwania, MD, professor of medicine, University of California, San Francisco, told this news organization.
Dr. Deedwania and others have published data on patients with diabetes that showed that treatment with high-intensity atorvastatin was associated with significant reductions in major adverse cardiovascular events.
“Here they use non-HDL cholesterol as a target. The NICE guidelines are the only guidelines looking at non-HDL cholesterol; however, all guidelines suggest an LDL to be less than 70 in all people with diabetes, and for those with recent acute coronary syndromes, the latest evidence suggests the LDL should actually be less than 50,” said Dr. Deedwania, spokesperson for the AHA and ACC.
As far as which measure to use, he believes both are useful. “It’s six of one and half a dozen of the other, in my opinion. The societies have not recommended non-HDL cholesterol and it’s easier to stay with what is readily available for clinicians, and using LDL cholesterol is still okay. The results of this analysis are confirmatory, in that looking at non-HDL cholesterol gives results very similar to what these statins have shown for their effect on LDL cholesterol,” he said.
Non-HDL cholesterol a better marker?
For Robert Rosenson, MD, director of metabolism and lipids at Mount Sinai Health System and professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai, New York, non-HDL cholesterol is becoming an important marker of risk for several reasons.
“The focus on LDL cholesterol has been due to the causal relationship of LDL with atherosclerotic cardiovascular disease, but in the last few decades, non-HDL has emerged because more people are overweight, have insulin resistance, and have diabetes,” Dr. Rosenson told this news organization. “In those situations, the LDL cholesterol underrepresents the risk of the LDL particles. With insulin resistance, the particles become more triglycerides and less cholesterol, so on a per-particle basis, you need to get more LDL particles to get to a certain LDL cholesterol concentration.”
Non-HDL cholesterol testing does not require fasting, another advantage of using it to monitor cholesterol, he added.
What is often forgotten is that moderate- to high-intensity statins have very good triglyceride-lowering effects, Dr. Rosenson said.
“This article highlights that, by using higher doses, you get more triglyceride-lowering. Hopefully, this will get practitioners to recognize that non-HDL cholesterol is a better predictor of risk in people with diabetes,” he said.
The study was funded by the National Institute for Health Research. Dr. Hodkinson, Dr. Rosenson, and Dr. Deedwania report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Avocados linked to lower cardiovascular risk
A prospective study that followed more than 110,000 men and women for more than 30 years suggests that .
Researchers also found that replacing half a serving of butter, cheese, bacon, or other animal product with an equivalent amount of avocado was associated with up to 22% lower risk for CVD events.
The findings add to evidence from other studies that has shown that avocados – which contain multiple nutrients, including fiber and unsaturated, healthy fats – have a positive impact on cardiovascular risk factors, first author Lorena S. Pacheco, PhD, a postdoctoral research fellow at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.
“This research complements and expands on the current literature that we have on unsaturated fats and reduced risk of cardiovascular disease and also underscores how bad saturated fats, like butter, cheese, and processed meats are for the heart,” Dr. Pacheco said.
“For the most part, we have known that avocados are healthy, but I think this study, because of its numbers and duration, adds a little more substance to that knowledge now,” Dr. Pacheco said.
The findings were published online March 30 in the Journal of the American Heart Association.
Avocados are dense with nutrients. They are high in fat, but in monounsaturated fats (MUFAs) and polyunsaturated fats (PUFAs), which are viewed as good.
A medium-sized (136 g) Haas avocado, which is the most commonly consumed avocado in the United States, contains roughly 13 g of oleic acid. Avocados also contain dietary fiber, potassium, magnesium, phytonutrients, and bioactive compounds.
To see the effect avocados can have on cardiovascular health, Dr. Pacheco and her team turned to two large, long-running cohort studies: the Nurses’ Health Study (NHS), which began in the early 1970s with 68,786 women 30-55 years of age; and the Health Professionals Follow-up Study (HPFS), which ran from 1986 to 2016 and followed 41,701 men 40-75 years of age.
All were free of cancer, coronary heart disease, and stroke at study entry.
Participants completed a validated food frequency questionnaire at baseline and every 4 years thereafter. The questionnaire asked about the amount and frequency of avocado consumed. One serving equaled half an avocado, or half a cup.
In the early days of the NHS, very few participants said they ate avocados, but that began to change over the years, as the popularity of avocados grew.
“The NHS cohort was recruited back in the late ‘70s, and the health professionals cohort did not start until the mid 1980s, when avocado consumption was really low,” Dr. Pacheco said.
“What is beautiful about these cohorts is we are able to ask participants questions and then save the answers that they give us throughout the years to answer questions that might arise whenever the question is right. So it just depends on when you accrue enough data to ask those questions about potential cardiovascular benefit with avocados,” she said.
There were 9,185 coronary heart disease events and 5,290 strokes documented over 30 years of follow-up.
After adjustment for lifestyle and other dietary factors, those with a higher avocado intake – at least two servings per week – had a 16% lower risk for CVD (pooled hazard ratio, 0.84; 95% CI, 0.75-0.95) and a 21% lower risk for coronary heart disease (pooled HR, 0.79; 95% CI, 0.68-0.91).
No significant associations were seen for stroke, but this is because the study did not have sufficient numbers, Dr. Pacheco explained.
A statistical model also determined that replacing half a serving daily of margarine, butter, egg, yogurt, cheese, or processed meats, such as bacon, with the same amount of avocado was associated with a 16%-22% lower risk for CVD events.
“I want to emphasize that the study is an epidemiological observational study and cannot prove cause and effect,” Dr. Pacheco said.
“It’s not a clinical trial – it’s based on observational epidemiology – but we saw patterns in the model: Avocado consumption and substituting avocado for other unhealthy fats reduced the risk of having a cardiovascular event or coronary heart disease,” she said.
The findings are significant “because a healthy dietary pattern is the cornerstone for cardiovascular health; however, it can be difficult for many Americans to achieve and adhere to healthy eating patterns,” Cheryl Anderson, PhD, professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, who is chair of the AHA’s Council on Epidemiology and Prevention, said in a statement.
“We desperately need strategies to improve intake of AHA-recommended healthy diets, such as the Mediterranean diet, that are rich in vegetables and fruits. Although no one food is the solution to routinely eating a healthy diet, this study is evidence that avocados have possible health benefits. This is promising because it is a food item that is popular, accessible, desirable, and easy to include in meals eaten by many Americans at home and in restaurants,” said Dr. Anderson, who was not part of the study.
Dr. Pacheco and Dr. Anderson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A prospective study that followed more than 110,000 men and women for more than 30 years suggests that .
Researchers also found that replacing half a serving of butter, cheese, bacon, or other animal product with an equivalent amount of avocado was associated with up to 22% lower risk for CVD events.
The findings add to evidence from other studies that has shown that avocados – which contain multiple nutrients, including fiber and unsaturated, healthy fats – have a positive impact on cardiovascular risk factors, first author Lorena S. Pacheco, PhD, a postdoctoral research fellow at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.
“This research complements and expands on the current literature that we have on unsaturated fats and reduced risk of cardiovascular disease and also underscores how bad saturated fats, like butter, cheese, and processed meats are for the heart,” Dr. Pacheco said.
“For the most part, we have known that avocados are healthy, but I think this study, because of its numbers and duration, adds a little more substance to that knowledge now,” Dr. Pacheco said.
The findings were published online March 30 in the Journal of the American Heart Association.
Avocados are dense with nutrients. They are high in fat, but in monounsaturated fats (MUFAs) and polyunsaturated fats (PUFAs), which are viewed as good.
A medium-sized (136 g) Haas avocado, which is the most commonly consumed avocado in the United States, contains roughly 13 g of oleic acid. Avocados also contain dietary fiber, potassium, magnesium, phytonutrients, and bioactive compounds.
To see the effect avocados can have on cardiovascular health, Dr. Pacheco and her team turned to two large, long-running cohort studies: the Nurses’ Health Study (NHS), which began in the early 1970s with 68,786 women 30-55 years of age; and the Health Professionals Follow-up Study (HPFS), which ran from 1986 to 2016 and followed 41,701 men 40-75 years of age.
All were free of cancer, coronary heart disease, and stroke at study entry.
Participants completed a validated food frequency questionnaire at baseline and every 4 years thereafter. The questionnaire asked about the amount and frequency of avocado consumed. One serving equaled half an avocado, or half a cup.
In the early days of the NHS, very few participants said they ate avocados, but that began to change over the years, as the popularity of avocados grew.
“The NHS cohort was recruited back in the late ‘70s, and the health professionals cohort did not start until the mid 1980s, when avocado consumption was really low,” Dr. Pacheco said.
“What is beautiful about these cohorts is we are able to ask participants questions and then save the answers that they give us throughout the years to answer questions that might arise whenever the question is right. So it just depends on when you accrue enough data to ask those questions about potential cardiovascular benefit with avocados,” she said.
There were 9,185 coronary heart disease events and 5,290 strokes documented over 30 years of follow-up.
After adjustment for lifestyle and other dietary factors, those with a higher avocado intake – at least two servings per week – had a 16% lower risk for CVD (pooled hazard ratio, 0.84; 95% CI, 0.75-0.95) and a 21% lower risk for coronary heart disease (pooled HR, 0.79; 95% CI, 0.68-0.91).
No significant associations were seen for stroke, but this is because the study did not have sufficient numbers, Dr. Pacheco explained.
A statistical model also determined that replacing half a serving daily of margarine, butter, egg, yogurt, cheese, or processed meats, such as bacon, with the same amount of avocado was associated with a 16%-22% lower risk for CVD events.
“I want to emphasize that the study is an epidemiological observational study and cannot prove cause and effect,” Dr. Pacheco said.
“It’s not a clinical trial – it’s based on observational epidemiology – but we saw patterns in the model: Avocado consumption and substituting avocado for other unhealthy fats reduced the risk of having a cardiovascular event or coronary heart disease,” she said.
The findings are significant “because a healthy dietary pattern is the cornerstone for cardiovascular health; however, it can be difficult for many Americans to achieve and adhere to healthy eating patterns,” Cheryl Anderson, PhD, professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, who is chair of the AHA’s Council on Epidemiology and Prevention, said in a statement.
“We desperately need strategies to improve intake of AHA-recommended healthy diets, such as the Mediterranean diet, that are rich in vegetables and fruits. Although no one food is the solution to routinely eating a healthy diet, this study is evidence that avocados have possible health benefits. This is promising because it is a food item that is popular, accessible, desirable, and easy to include in meals eaten by many Americans at home and in restaurants,” said Dr. Anderson, who was not part of the study.
Dr. Pacheco and Dr. Anderson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A prospective study that followed more than 110,000 men and women for more than 30 years suggests that .
Researchers also found that replacing half a serving of butter, cheese, bacon, or other animal product with an equivalent amount of avocado was associated with up to 22% lower risk for CVD events.
The findings add to evidence from other studies that has shown that avocados – which contain multiple nutrients, including fiber and unsaturated, healthy fats – have a positive impact on cardiovascular risk factors, first author Lorena S. Pacheco, PhD, a postdoctoral research fellow at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.
“This research complements and expands on the current literature that we have on unsaturated fats and reduced risk of cardiovascular disease and also underscores how bad saturated fats, like butter, cheese, and processed meats are for the heart,” Dr. Pacheco said.
“For the most part, we have known that avocados are healthy, but I think this study, because of its numbers and duration, adds a little more substance to that knowledge now,” Dr. Pacheco said.
The findings were published online March 30 in the Journal of the American Heart Association.
Avocados are dense with nutrients. They are high in fat, but in monounsaturated fats (MUFAs) and polyunsaturated fats (PUFAs), which are viewed as good.
A medium-sized (136 g) Haas avocado, which is the most commonly consumed avocado in the United States, contains roughly 13 g of oleic acid. Avocados also contain dietary fiber, potassium, magnesium, phytonutrients, and bioactive compounds.
To see the effect avocados can have on cardiovascular health, Dr. Pacheco and her team turned to two large, long-running cohort studies: the Nurses’ Health Study (NHS), which began in the early 1970s with 68,786 women 30-55 years of age; and the Health Professionals Follow-up Study (HPFS), which ran from 1986 to 2016 and followed 41,701 men 40-75 years of age.
All were free of cancer, coronary heart disease, and stroke at study entry.
Participants completed a validated food frequency questionnaire at baseline and every 4 years thereafter. The questionnaire asked about the amount and frequency of avocado consumed. One serving equaled half an avocado, or half a cup.
In the early days of the NHS, very few participants said they ate avocados, but that began to change over the years, as the popularity of avocados grew.
“The NHS cohort was recruited back in the late ‘70s, and the health professionals cohort did not start until the mid 1980s, when avocado consumption was really low,” Dr. Pacheco said.
“What is beautiful about these cohorts is we are able to ask participants questions and then save the answers that they give us throughout the years to answer questions that might arise whenever the question is right. So it just depends on when you accrue enough data to ask those questions about potential cardiovascular benefit with avocados,” she said.
There were 9,185 coronary heart disease events and 5,290 strokes documented over 30 years of follow-up.
After adjustment for lifestyle and other dietary factors, those with a higher avocado intake – at least two servings per week – had a 16% lower risk for CVD (pooled hazard ratio, 0.84; 95% CI, 0.75-0.95) and a 21% lower risk for coronary heart disease (pooled HR, 0.79; 95% CI, 0.68-0.91).
No significant associations were seen for stroke, but this is because the study did not have sufficient numbers, Dr. Pacheco explained.
A statistical model also determined that replacing half a serving daily of margarine, butter, egg, yogurt, cheese, or processed meats, such as bacon, with the same amount of avocado was associated with a 16%-22% lower risk for CVD events.
“I want to emphasize that the study is an epidemiological observational study and cannot prove cause and effect,” Dr. Pacheco said.
“It’s not a clinical trial – it’s based on observational epidemiology – but we saw patterns in the model: Avocado consumption and substituting avocado for other unhealthy fats reduced the risk of having a cardiovascular event or coronary heart disease,” she said.
The findings are significant “because a healthy dietary pattern is the cornerstone for cardiovascular health; however, it can be difficult for many Americans to achieve and adhere to healthy eating patterns,” Cheryl Anderson, PhD, professor and dean of the Herbert Wertheim School of Public Health and Human Longevity Science at the University of California, San Diego, who is chair of the AHA’s Council on Epidemiology and Prevention, said in a statement.
“We desperately need strategies to improve intake of AHA-recommended healthy diets, such as the Mediterranean diet, that are rich in vegetables and fruits. Although no one food is the solution to routinely eating a healthy diet, this study is evidence that avocados have possible health benefits. This is promising because it is a food item that is popular, accessible, desirable, and easy to include in meals eaten by many Americans at home and in restaurants,” said Dr. Anderson, who was not part of the study.
Dr. Pacheco and Dr. Anderson report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Cardiologists say rights to maternity leave violated
A survey of 323 women cardiologists who were working while they were pregnant showed that nearly 75% experienced discriminatory maternity-leave practices, some of which were likely violations of the Family and Medical Leave Act (FMLA).
More than 40% saw their salaries decreased during their year of pregnancy, 38% were required to perform extra service or call before taking maternity leave, exposing them to occupational hazards such as radiation, and 40% experienced a pregnancy complication, significantly higher than the general population and other medical specialties.
Additionally, of those who performed extra service or call, 18% were placed on bedrest before delivery, compared with 7.4% who did not perform extra service or call.
More than half of respondents reported that pregnancy negatively impacted their careers, and 42.4% said they experienced pressure to return to work and a delay in promotions, both illegal practices under the FMLA.
The survey is published in the Journal of the American College of Cardiology.
“Childbearing is difficult for women in cardiology with more than double the rate of gestational complications of the U.S. population, frequent income loss out of proportion to reduced productivity, and for nearly half, has an adverse impact on their career,” lead author Martha Gulati, MD, University of Arizona, Phoenix, said in a statement.
“While many professions struggle to create environments supportive of pregnancy and child-rearing, the prevalence of illegal behavior in cardiology is quite high and presents substantial legal risk for employers,” Dr. Gulati added.
C. Noel Bairey Merz, MD, professor of cardiology at Cedars-Sinai Smidt Heart Institute, Los Angeles, and a coauthor of the survey, told this news organization that it’s not surprising that such a situation exists, even “in this day and age.”
“I’m not surprised as a woman in cardiology myself. I was told by my training director that if I took off more than my allowed sick leave when I had my first and second children, I would have to repeat the year of training, so not surprised at all. I hear this from colleagues all the time,” Dr. Bairey Merz said.
The exchange left her feeling fearful for her career.
“Who wants to repeat a year? It pushes you back from a career standpoint, financially, everything. It also made me angry. I had a colleague who busted his leg in a motorcycle accident. He was unable to do any procedures for 16 weeks, and he didn’t have to repeat the year,” she pointed out.
The challenge that pregnancy represents is frequently cited by women as a deterrent for applying for a cardiology fellowship, Laxmi S. Mehta, MD, Ohio State University, Columbus, and colleagues wrote in an accompanying editorial.
The findings from the survey “reveal restrictive maternity leave data in a profession that has historically and currently continues to have a diversity problem,” they wrote.
“Maternity and pregnancy issues are a thing in cardiology,” Dr. Mehta said in an interview. “It’s one of the reasons why women get deterred from going into the field. It makes it challenging to choose cardiology if you perceive that the culture is negative, that it’s hard to be pregnant, or to bear children, or to take care of them post partum. It is problematic and it should not be occurring now.”
Leadership that condones such restrictive policies or even promotes them through ignorance and inaction needs to be held accountable, she added.
“We need to move forward from this negativity and make it more warm and welcoming to have families, whether you are a trainee or a practicing cardiologist, male or female. We need transparent and consistent parental leave policies and things like lactation support when a woman returns to work. That is a big issue,” Dr. Mehta said.
Having cardiovascular leaders champion the cause of adequate maternity and paternity leave are crucial to creating a newer, inclusive environment in cardiology.
As an example, Dr. Mehta recounted her own experience when she was in training 17 years ago.
“When I interviewed for a cardiology fellowship, one of the female program directors asked me if I was planning to have children, because if I did, the other fellows wouldn’t like it if they had to cover for me,” she said. “I ended up doing my fellowship where the chief of cardiology encouraged me to have children. He said: ‘Have your children during training, we will support you.’ And he did. I still had to do all of the call make-up and that stuff, but I worked in a supportive environment, and it made all the difference.”
“It’s about allyship,” she added. “You will have some people who are supportive and some who are not, but when you have the chief supporting you, you have a strong ally.”
The researchers suggest that one strategy is to temporarily replace cardiologists on maternity leave with locums, or “deepen the bench of coverage for clinical work, as is done for other absences. Given the expanding coverage of parental and family medical leaves, and awareness of these issues nationally, the need for this is likely to become less of an exception and more the rule.”
For example, nine states and Washington, D.C. now provide paid parental leave, they wrote, “and there is pending legislation in others.”
Dr. Bairey Merz and Dr. Mehta reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A survey of 323 women cardiologists who were working while they were pregnant showed that nearly 75% experienced discriminatory maternity-leave practices, some of which were likely violations of the Family and Medical Leave Act (FMLA).
More than 40% saw their salaries decreased during their year of pregnancy, 38% were required to perform extra service or call before taking maternity leave, exposing them to occupational hazards such as radiation, and 40% experienced a pregnancy complication, significantly higher than the general population and other medical specialties.
Additionally, of those who performed extra service or call, 18% were placed on bedrest before delivery, compared with 7.4% who did not perform extra service or call.
More than half of respondents reported that pregnancy negatively impacted their careers, and 42.4% said they experienced pressure to return to work and a delay in promotions, both illegal practices under the FMLA.
The survey is published in the Journal of the American College of Cardiology.
“Childbearing is difficult for women in cardiology with more than double the rate of gestational complications of the U.S. population, frequent income loss out of proportion to reduced productivity, and for nearly half, has an adverse impact on their career,” lead author Martha Gulati, MD, University of Arizona, Phoenix, said in a statement.
“While many professions struggle to create environments supportive of pregnancy and child-rearing, the prevalence of illegal behavior in cardiology is quite high and presents substantial legal risk for employers,” Dr. Gulati added.
C. Noel Bairey Merz, MD, professor of cardiology at Cedars-Sinai Smidt Heart Institute, Los Angeles, and a coauthor of the survey, told this news organization that it’s not surprising that such a situation exists, even “in this day and age.”
“I’m not surprised as a woman in cardiology myself. I was told by my training director that if I took off more than my allowed sick leave when I had my first and second children, I would have to repeat the year of training, so not surprised at all. I hear this from colleagues all the time,” Dr. Bairey Merz said.
The exchange left her feeling fearful for her career.
“Who wants to repeat a year? It pushes you back from a career standpoint, financially, everything. It also made me angry. I had a colleague who busted his leg in a motorcycle accident. He was unable to do any procedures for 16 weeks, and he didn’t have to repeat the year,” she pointed out.
The challenge that pregnancy represents is frequently cited by women as a deterrent for applying for a cardiology fellowship, Laxmi S. Mehta, MD, Ohio State University, Columbus, and colleagues wrote in an accompanying editorial.
The findings from the survey “reveal restrictive maternity leave data in a profession that has historically and currently continues to have a diversity problem,” they wrote.
“Maternity and pregnancy issues are a thing in cardiology,” Dr. Mehta said in an interview. “It’s one of the reasons why women get deterred from going into the field. It makes it challenging to choose cardiology if you perceive that the culture is negative, that it’s hard to be pregnant, or to bear children, or to take care of them post partum. It is problematic and it should not be occurring now.”
Leadership that condones such restrictive policies or even promotes them through ignorance and inaction needs to be held accountable, she added.
“We need to move forward from this negativity and make it more warm and welcoming to have families, whether you are a trainee or a practicing cardiologist, male or female. We need transparent and consistent parental leave policies and things like lactation support when a woman returns to work. That is a big issue,” Dr. Mehta said.
Having cardiovascular leaders champion the cause of adequate maternity and paternity leave are crucial to creating a newer, inclusive environment in cardiology.
As an example, Dr. Mehta recounted her own experience when she was in training 17 years ago.
“When I interviewed for a cardiology fellowship, one of the female program directors asked me if I was planning to have children, because if I did, the other fellows wouldn’t like it if they had to cover for me,” she said. “I ended up doing my fellowship where the chief of cardiology encouraged me to have children. He said: ‘Have your children during training, we will support you.’ And he did. I still had to do all of the call make-up and that stuff, but I worked in a supportive environment, and it made all the difference.”
“It’s about allyship,” she added. “You will have some people who are supportive and some who are not, but when you have the chief supporting you, you have a strong ally.”
The researchers suggest that one strategy is to temporarily replace cardiologists on maternity leave with locums, or “deepen the bench of coverage for clinical work, as is done for other absences. Given the expanding coverage of parental and family medical leaves, and awareness of these issues nationally, the need for this is likely to become less of an exception and more the rule.”
For example, nine states and Washington, D.C. now provide paid parental leave, they wrote, “and there is pending legislation in others.”
Dr. Bairey Merz and Dr. Mehta reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A survey of 323 women cardiologists who were working while they were pregnant showed that nearly 75% experienced discriminatory maternity-leave practices, some of which were likely violations of the Family and Medical Leave Act (FMLA).
More than 40% saw their salaries decreased during their year of pregnancy, 38% were required to perform extra service or call before taking maternity leave, exposing them to occupational hazards such as radiation, and 40% experienced a pregnancy complication, significantly higher than the general population and other medical specialties.
Additionally, of those who performed extra service or call, 18% were placed on bedrest before delivery, compared with 7.4% who did not perform extra service or call.
More than half of respondents reported that pregnancy negatively impacted their careers, and 42.4% said they experienced pressure to return to work and a delay in promotions, both illegal practices under the FMLA.
The survey is published in the Journal of the American College of Cardiology.
“Childbearing is difficult for women in cardiology with more than double the rate of gestational complications of the U.S. population, frequent income loss out of proportion to reduced productivity, and for nearly half, has an adverse impact on their career,” lead author Martha Gulati, MD, University of Arizona, Phoenix, said in a statement.
“While many professions struggle to create environments supportive of pregnancy and child-rearing, the prevalence of illegal behavior in cardiology is quite high and presents substantial legal risk for employers,” Dr. Gulati added.
C. Noel Bairey Merz, MD, professor of cardiology at Cedars-Sinai Smidt Heart Institute, Los Angeles, and a coauthor of the survey, told this news organization that it’s not surprising that such a situation exists, even “in this day and age.”
“I’m not surprised as a woman in cardiology myself. I was told by my training director that if I took off more than my allowed sick leave when I had my first and second children, I would have to repeat the year of training, so not surprised at all. I hear this from colleagues all the time,” Dr. Bairey Merz said.
The exchange left her feeling fearful for her career.
“Who wants to repeat a year? It pushes you back from a career standpoint, financially, everything. It also made me angry. I had a colleague who busted his leg in a motorcycle accident. He was unable to do any procedures for 16 weeks, and he didn’t have to repeat the year,” she pointed out.
The challenge that pregnancy represents is frequently cited by women as a deterrent for applying for a cardiology fellowship, Laxmi S. Mehta, MD, Ohio State University, Columbus, and colleagues wrote in an accompanying editorial.
The findings from the survey “reveal restrictive maternity leave data in a profession that has historically and currently continues to have a diversity problem,” they wrote.
“Maternity and pregnancy issues are a thing in cardiology,” Dr. Mehta said in an interview. “It’s one of the reasons why women get deterred from going into the field. It makes it challenging to choose cardiology if you perceive that the culture is negative, that it’s hard to be pregnant, or to bear children, or to take care of them post partum. It is problematic and it should not be occurring now.”
Leadership that condones such restrictive policies or even promotes them through ignorance and inaction needs to be held accountable, she added.
“We need to move forward from this negativity and make it more warm and welcoming to have families, whether you are a trainee or a practicing cardiologist, male or female. We need transparent and consistent parental leave policies and things like lactation support when a woman returns to work. That is a big issue,” Dr. Mehta said.
Having cardiovascular leaders champion the cause of adequate maternity and paternity leave are crucial to creating a newer, inclusive environment in cardiology.
As an example, Dr. Mehta recounted her own experience when she was in training 17 years ago.
“When I interviewed for a cardiology fellowship, one of the female program directors asked me if I was planning to have children, because if I did, the other fellows wouldn’t like it if they had to cover for me,” she said. “I ended up doing my fellowship where the chief of cardiology encouraged me to have children. He said: ‘Have your children during training, we will support you.’ And he did. I still had to do all of the call make-up and that stuff, but I worked in a supportive environment, and it made all the difference.”
“It’s about allyship,” she added. “You will have some people who are supportive and some who are not, but when you have the chief supporting you, you have a strong ally.”
The researchers suggest that one strategy is to temporarily replace cardiologists on maternity leave with locums, or “deepen the bench of coverage for clinical work, as is done for other absences. Given the expanding coverage of parental and family medical leaves, and awareness of these issues nationally, the need for this is likely to become less of an exception and more the rule.”
For example, nine states and Washington, D.C. now provide paid parental leave, they wrote, “and there is pending legislation in others.”
Dr. Bairey Merz and Dr. Mehta reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
Women still missing from CV clinical trial leadership
Although women were well represented on panels, and chaired or cochaired sessions, thanks to the ACC’s ongoing efforts to promote gender diversity and inclusion, they rarely got to give the big talks.
“Unfortunately, women continue to be underrepresented among CV clinical trial leadership, leading to a lack of subject diversity,” Mary Norine Walsh, MD, medical director of heart failure and cardiac transplantation at Ascension St. Vincent Heart Center, Indianapolis, Ind., wrote in a review published online Feb. 28 in the Journal of the American College of Cardiology.
An analysis of cardiovascular trials published during the past 4 years showed that women comprised only 10.1% of clinical trial leadership committees, and more than half of the trials had no women at all as part of the trial leadership team. About 10% of the trials had a woman as first or senior author.
In an interview, Dr. Walsh said she was prompted to write her review because she found the absence of women presenters at ACC 21 so striking.
“ACC 21 was held virtually because of COVID. This gave me the opportunity to easily view all of the research sessions. I attended all of the late-breaking clinical trials and featured clinical research sessions live while they were being presented, and it slowly dawned on me as I was watching that the vast majority of the presenters were men,” she said.
“The ACC does what it can to ensure a good gender mix of panelists and session chairs, but what it cannot control is who presents the data. The fact that 93% of these talks were given by men was astonishing to me,” Dr. Walsh said.
Of the three trials presented by women, one was on sex-specific outcomes in high-risk patients receiving ticagrelor with or without aspirin after percutaneous coronary intervention (a subanalysis of the TWILIGHT study); one was on the impact of COVID-19 on the global cardiovascular workforce (the ACC 2020 Well Being Study); and one was on the prevention of cardiac dysfunction during adjuvanttherapy with candesartan and metoprolol (the PRADA study).
Most of the presenters were regulars at the ACC podium. As Dr. Walsh observed: “This was assuredly not the inaugural turn at the international podium for these male trial presenters.”
So why are women so noticeably absent among the leaders of cardiovascular clinical trials research?
The root cause for this underrepresentation begins with the low number of women who lead clinical trials in cardiovascular medicine and surgery, and the fact that there are fewer female cardiologists than male cardiologists to begin with.
Then there is the lack of mentorship, which, Dr. Walsh said, “really does occur along gendered lines, with men mentoring men.”
In addition, industry-funded trials tend to feed a nondiverse investigator pipeline and other research collaborations often encompass established networks, Dr. Walsh noted.
“When industry is embarking on a new trial of a drug or device, it tends to lean back on who they have had led before. It really gets down to who you know, so getting new people in is fairly difficult,” she said.
Several initiatives to increase diversity in CV clinical trial leadership are ongoing by the ACC and other organizations.
For example, Women as One gives “escalator awards” to boost or escalate the training of highly qualified female cardiologists through targeted funding, mentorship, and networking.
The ACC’s “Clinical Trial Research: Upping Your Game” program aims to develop and train the next generation of a diverse and inclusive clinical trials workforce, focusing not only on women but on other traditionally underrepresented groups.
“We’re now in our third cohort of investigators who are early in their careers. We’re arming them with the skills to become successful in becoming investigators and then going up the chain to trial leadership. We are focusing our efforts on those who are underrepresented in cardiology – women, native Americans, Latinx, and Black investigators. We are hoping to increase diversity through that way, but more still needs to be done,” she said.
Trial sponsors, whether federally funded or industry sponsored, need to insist on diversity of the trial steering committee, and principal investigators need to consider diversity.
“A rethinking of who is eligible to present important trial results is needed,” Dr. Walsh said.
“The informal, or formal, pecking order of CV trial leadership needs to be reworked. All members of the steering committee should be possible presenters, and women should not be asked to report late-breaking results of trials that are reporting sex-specific results or data that are pertinent only to a female population.”
A version of this article first appeared on Medscape.com.
Although women were well represented on panels, and chaired or cochaired sessions, thanks to the ACC’s ongoing efforts to promote gender diversity and inclusion, they rarely got to give the big talks.
“Unfortunately, women continue to be underrepresented among CV clinical trial leadership, leading to a lack of subject diversity,” Mary Norine Walsh, MD, medical director of heart failure and cardiac transplantation at Ascension St. Vincent Heart Center, Indianapolis, Ind., wrote in a review published online Feb. 28 in the Journal of the American College of Cardiology.
An analysis of cardiovascular trials published during the past 4 years showed that women comprised only 10.1% of clinical trial leadership committees, and more than half of the trials had no women at all as part of the trial leadership team. About 10% of the trials had a woman as first or senior author.
In an interview, Dr. Walsh said she was prompted to write her review because she found the absence of women presenters at ACC 21 so striking.
“ACC 21 was held virtually because of COVID. This gave me the opportunity to easily view all of the research sessions. I attended all of the late-breaking clinical trials and featured clinical research sessions live while they were being presented, and it slowly dawned on me as I was watching that the vast majority of the presenters were men,” she said.
“The ACC does what it can to ensure a good gender mix of panelists and session chairs, but what it cannot control is who presents the data. The fact that 93% of these talks were given by men was astonishing to me,” Dr. Walsh said.
Of the three trials presented by women, one was on sex-specific outcomes in high-risk patients receiving ticagrelor with or without aspirin after percutaneous coronary intervention (a subanalysis of the TWILIGHT study); one was on the impact of COVID-19 on the global cardiovascular workforce (the ACC 2020 Well Being Study); and one was on the prevention of cardiac dysfunction during adjuvanttherapy with candesartan and metoprolol (the PRADA study).
Most of the presenters were regulars at the ACC podium. As Dr. Walsh observed: “This was assuredly not the inaugural turn at the international podium for these male trial presenters.”
So why are women so noticeably absent among the leaders of cardiovascular clinical trials research?
The root cause for this underrepresentation begins with the low number of women who lead clinical trials in cardiovascular medicine and surgery, and the fact that there are fewer female cardiologists than male cardiologists to begin with.
Then there is the lack of mentorship, which, Dr. Walsh said, “really does occur along gendered lines, with men mentoring men.”
In addition, industry-funded trials tend to feed a nondiverse investigator pipeline and other research collaborations often encompass established networks, Dr. Walsh noted.
“When industry is embarking on a new trial of a drug or device, it tends to lean back on who they have had led before. It really gets down to who you know, so getting new people in is fairly difficult,” she said.
Several initiatives to increase diversity in CV clinical trial leadership are ongoing by the ACC and other organizations.
For example, Women as One gives “escalator awards” to boost or escalate the training of highly qualified female cardiologists through targeted funding, mentorship, and networking.
The ACC’s “Clinical Trial Research: Upping Your Game” program aims to develop and train the next generation of a diverse and inclusive clinical trials workforce, focusing not only on women but on other traditionally underrepresented groups.
“We’re now in our third cohort of investigators who are early in their careers. We’re arming them with the skills to become successful in becoming investigators and then going up the chain to trial leadership. We are focusing our efforts on those who are underrepresented in cardiology – women, native Americans, Latinx, and Black investigators. We are hoping to increase diversity through that way, but more still needs to be done,” she said.
Trial sponsors, whether federally funded or industry sponsored, need to insist on diversity of the trial steering committee, and principal investigators need to consider diversity.
“A rethinking of who is eligible to present important trial results is needed,” Dr. Walsh said.
“The informal, or formal, pecking order of CV trial leadership needs to be reworked. All members of the steering committee should be possible presenters, and women should not be asked to report late-breaking results of trials that are reporting sex-specific results or data that are pertinent only to a female population.”
A version of this article first appeared on Medscape.com.
Although women were well represented on panels, and chaired or cochaired sessions, thanks to the ACC’s ongoing efforts to promote gender diversity and inclusion, they rarely got to give the big talks.
“Unfortunately, women continue to be underrepresented among CV clinical trial leadership, leading to a lack of subject diversity,” Mary Norine Walsh, MD, medical director of heart failure and cardiac transplantation at Ascension St. Vincent Heart Center, Indianapolis, Ind., wrote in a review published online Feb. 28 in the Journal of the American College of Cardiology.
An analysis of cardiovascular trials published during the past 4 years showed that women comprised only 10.1% of clinical trial leadership committees, and more than half of the trials had no women at all as part of the trial leadership team. About 10% of the trials had a woman as first or senior author.
In an interview, Dr. Walsh said she was prompted to write her review because she found the absence of women presenters at ACC 21 so striking.
“ACC 21 was held virtually because of COVID. This gave me the opportunity to easily view all of the research sessions. I attended all of the late-breaking clinical trials and featured clinical research sessions live while they were being presented, and it slowly dawned on me as I was watching that the vast majority of the presenters were men,” she said.
“The ACC does what it can to ensure a good gender mix of panelists and session chairs, but what it cannot control is who presents the data. The fact that 93% of these talks were given by men was astonishing to me,” Dr. Walsh said.
Of the three trials presented by women, one was on sex-specific outcomes in high-risk patients receiving ticagrelor with or without aspirin after percutaneous coronary intervention (a subanalysis of the TWILIGHT study); one was on the impact of COVID-19 on the global cardiovascular workforce (the ACC 2020 Well Being Study); and one was on the prevention of cardiac dysfunction during adjuvanttherapy with candesartan and metoprolol (the PRADA study).
Most of the presenters were regulars at the ACC podium. As Dr. Walsh observed: “This was assuredly not the inaugural turn at the international podium for these male trial presenters.”
So why are women so noticeably absent among the leaders of cardiovascular clinical trials research?
The root cause for this underrepresentation begins with the low number of women who lead clinical trials in cardiovascular medicine and surgery, and the fact that there are fewer female cardiologists than male cardiologists to begin with.
Then there is the lack of mentorship, which, Dr. Walsh said, “really does occur along gendered lines, with men mentoring men.”
In addition, industry-funded trials tend to feed a nondiverse investigator pipeline and other research collaborations often encompass established networks, Dr. Walsh noted.
“When industry is embarking on a new trial of a drug or device, it tends to lean back on who they have had led before. It really gets down to who you know, so getting new people in is fairly difficult,” she said.
Several initiatives to increase diversity in CV clinical trial leadership are ongoing by the ACC and other organizations.
For example, Women as One gives “escalator awards” to boost or escalate the training of highly qualified female cardiologists through targeted funding, mentorship, and networking.
The ACC’s “Clinical Trial Research: Upping Your Game” program aims to develop and train the next generation of a diverse and inclusive clinical trials workforce, focusing not only on women but on other traditionally underrepresented groups.
“We’re now in our third cohort of investigators who are early in their careers. We’re arming them with the skills to become successful in becoming investigators and then going up the chain to trial leadership. We are focusing our efforts on those who are underrepresented in cardiology – women, native Americans, Latinx, and Black investigators. We are hoping to increase diversity through that way, but more still needs to be done,” she said.
Trial sponsors, whether federally funded or industry sponsored, need to insist on diversity of the trial steering committee, and principal investigators need to consider diversity.
“A rethinking of who is eligible to present important trial results is needed,” Dr. Walsh said.
“The informal, or formal, pecking order of CV trial leadership needs to be reworked. All members of the steering committee should be possible presenters, and women should not be asked to report late-breaking results of trials that are reporting sex-specific results or data that are pertinent only to a female population.”
A version of this article first appeared on Medscape.com.
Treating young adults with high LDL may be cost-effective
Treating elevated low-density lipoprotein cholesterol (LDL-C) in adults younger than 40 with statins is highly cost-effective in men, and intermediately cost-effective in women, a new report suggests.
In a simulated model based on data from the U.S. National Health and Nutrition Examination Survey (NHANES), lipid lowering with statins or lifestyle interventions in this age group would prevent or reduce the risk of atherosclerotic cardiovascular disease (ASCVD) and improve quality of life in later years.
The findings were published online Nov. 8 in the Journal of the American College of Cardiology.
“My group does epidemiologic analyses with cohort studies as well as health economic analyses like this one, and if you have long-term longitudinal observation, you see that the early exposures are important for what happens later,” senior author Andrew E. Moran, MD, Columbia University Irving Medical Center, New York, told this news organization.
“But when it comes to treatment studies that a lot of the treatment guidelines are based on, those are usually short-term, and they usually enroll older people. We saw the gap in the evidence that this paper tries to fill,” Dr. Moran said.
His group used a computer simulation model to synthesize evidence from observational cohort studies and clinical trials of statin treatment, as well as health services data on the costs of medicines and treatments.
Combining information from these sources, the investigators made their best estimates of the potential health benefits and costs of treating high cholesterol earlier in life, compared with standard care, which was statin treatment at age 40, or if LDL-C was 190 mg/dL or greater.
Lipid lowering incremental to standard care with moderate-intensity statins or intensive lifestyle interventions was simulated starting when young adult LDL-C was either ≥160 mg/dL or ≥130 mg/dL.
They found that approximately 27% of young adults who are free of ASCVD have LDL-C ≥130 mg/dL, and 9% have LDL-C of ≥160 mg/dL.
Their model projected that treating adults younger than 40 with statins or lifestyle interventions would prevent lifetime ASCVD events and increase quality-adjusted life years (QALYs) compared with standard care, which would begin treatment at age 40.
Incremental cost-effectiveness ratios (ICERs) were $31,000/QALY for statin treatment in young adult men with LDL-C ≥130 mg/dL, and $106,000/QALY for statin treatment in young women with LDL-C ≥130 mg/dL.
Intensive lifestyle intervention was more costly and less effective than statin therapy.
“We are straining to find these young adults with very high cholesterol,” Dr. Moran noted. “A lot of young adults don’t even see a doctor. This is an argument for engaging them in their health care and getting them involved in some basic screening. Atherosclerosis is a long-term process that starts in childhood for a lot of people.”
More innovative approaches may be needed, because the traditional health care system is not doing a good job of reaching young adults, he added. “Many of them may not have adequate health insurance. They need health care in nontraditional ways; convenience is really important for them. Perhaps part of the solution here is to think about ways of reaching this particular group that is not engaged with health care generally.”
Time to relax the age 40 threshold
The U.S. Preventive Services Task Force and the American College of Cardiology/American Heart Association should emphasize lifetime risk of elevated cholesterol, Paul A. Heidenreich, MD, MS, Stanford University School of Medicine, California, and colleagues write in an accompanying editorial.
“In addition to calculating 10-year risk, we should calculate years of life lost (or QALYs lost) from unhealthy LDL-C levels, and both lifestyle and pharmacologic treatment should be considered to treat high LDL-C in adults regardless of age. We also need to communicate that the mantra ‘lower is better’ applies not only to a single measurement but to lifetime exposure to LDL-C,” the editorialists write.
“I think treatment should be earlier than age 40,” Dr. Heidenreich said in an interview.
“Part of the reason that 40 was chosen as a threshold was because everyone looked at 10-year, or even 20-year risk, and thought there was no reason to worry until you get older. It’s interesting that we never accepted that with high blood pressure. But more and more, we are learning that it is a lifelong process,” he said.
“Statins are getting less and less expensive, and their safety is more and more established with every decade that goes by. I definitely agree with this paper that it would actually make sense to be starting much earlier for those with elevated CVD risk from their high cholesterol.”
The study was supported by the U.S. National Heart, Lung, and Blood Institute (NHLBI), the Medical Research Council, Swindon, U.K. Dr. Moran and Dr. Heidenreich have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Treating elevated low-density lipoprotein cholesterol (LDL-C) in adults younger than 40 with statins is highly cost-effective in men, and intermediately cost-effective in women, a new report suggests.
In a simulated model based on data from the U.S. National Health and Nutrition Examination Survey (NHANES), lipid lowering with statins or lifestyle interventions in this age group would prevent or reduce the risk of atherosclerotic cardiovascular disease (ASCVD) and improve quality of life in later years.
The findings were published online Nov. 8 in the Journal of the American College of Cardiology.
“My group does epidemiologic analyses with cohort studies as well as health economic analyses like this one, and if you have long-term longitudinal observation, you see that the early exposures are important for what happens later,” senior author Andrew E. Moran, MD, Columbia University Irving Medical Center, New York, told this news organization.
“But when it comes to treatment studies that a lot of the treatment guidelines are based on, those are usually short-term, and they usually enroll older people. We saw the gap in the evidence that this paper tries to fill,” Dr. Moran said.
His group used a computer simulation model to synthesize evidence from observational cohort studies and clinical trials of statin treatment, as well as health services data on the costs of medicines and treatments.
Combining information from these sources, the investigators made their best estimates of the potential health benefits and costs of treating high cholesterol earlier in life, compared with standard care, which was statin treatment at age 40, or if LDL-C was 190 mg/dL or greater.
Lipid lowering incremental to standard care with moderate-intensity statins or intensive lifestyle interventions was simulated starting when young adult LDL-C was either ≥160 mg/dL or ≥130 mg/dL.
They found that approximately 27% of young adults who are free of ASCVD have LDL-C ≥130 mg/dL, and 9% have LDL-C of ≥160 mg/dL.
Their model projected that treating adults younger than 40 with statins or lifestyle interventions would prevent lifetime ASCVD events and increase quality-adjusted life years (QALYs) compared with standard care, which would begin treatment at age 40.
Incremental cost-effectiveness ratios (ICERs) were $31,000/QALY for statin treatment in young adult men with LDL-C ≥130 mg/dL, and $106,000/QALY for statin treatment in young women with LDL-C ≥130 mg/dL.
Intensive lifestyle intervention was more costly and less effective than statin therapy.
“We are straining to find these young adults with very high cholesterol,” Dr. Moran noted. “A lot of young adults don’t even see a doctor. This is an argument for engaging them in their health care and getting them involved in some basic screening. Atherosclerosis is a long-term process that starts in childhood for a lot of people.”
More innovative approaches may be needed, because the traditional health care system is not doing a good job of reaching young adults, he added. “Many of them may not have adequate health insurance. They need health care in nontraditional ways; convenience is really important for them. Perhaps part of the solution here is to think about ways of reaching this particular group that is not engaged with health care generally.”
Time to relax the age 40 threshold
The U.S. Preventive Services Task Force and the American College of Cardiology/American Heart Association should emphasize lifetime risk of elevated cholesterol, Paul A. Heidenreich, MD, MS, Stanford University School of Medicine, California, and colleagues write in an accompanying editorial.
“In addition to calculating 10-year risk, we should calculate years of life lost (or QALYs lost) from unhealthy LDL-C levels, and both lifestyle and pharmacologic treatment should be considered to treat high LDL-C in adults regardless of age. We also need to communicate that the mantra ‘lower is better’ applies not only to a single measurement but to lifetime exposure to LDL-C,” the editorialists write.
“I think treatment should be earlier than age 40,” Dr. Heidenreich said in an interview.
“Part of the reason that 40 was chosen as a threshold was because everyone looked at 10-year, or even 20-year risk, and thought there was no reason to worry until you get older. It’s interesting that we never accepted that with high blood pressure. But more and more, we are learning that it is a lifelong process,” he said.
“Statins are getting less and less expensive, and their safety is more and more established with every decade that goes by. I definitely agree with this paper that it would actually make sense to be starting much earlier for those with elevated CVD risk from their high cholesterol.”
The study was supported by the U.S. National Heart, Lung, and Blood Institute (NHLBI), the Medical Research Council, Swindon, U.K. Dr. Moran and Dr. Heidenreich have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Treating elevated low-density lipoprotein cholesterol (LDL-C) in adults younger than 40 with statins is highly cost-effective in men, and intermediately cost-effective in women, a new report suggests.
In a simulated model based on data from the U.S. National Health and Nutrition Examination Survey (NHANES), lipid lowering with statins or lifestyle interventions in this age group would prevent or reduce the risk of atherosclerotic cardiovascular disease (ASCVD) and improve quality of life in later years.
The findings were published online Nov. 8 in the Journal of the American College of Cardiology.
“My group does epidemiologic analyses with cohort studies as well as health economic analyses like this one, and if you have long-term longitudinal observation, you see that the early exposures are important for what happens later,” senior author Andrew E. Moran, MD, Columbia University Irving Medical Center, New York, told this news organization.
“But when it comes to treatment studies that a lot of the treatment guidelines are based on, those are usually short-term, and they usually enroll older people. We saw the gap in the evidence that this paper tries to fill,” Dr. Moran said.
His group used a computer simulation model to synthesize evidence from observational cohort studies and clinical trials of statin treatment, as well as health services data on the costs of medicines and treatments.
Combining information from these sources, the investigators made their best estimates of the potential health benefits and costs of treating high cholesterol earlier in life, compared with standard care, which was statin treatment at age 40, or if LDL-C was 190 mg/dL or greater.
Lipid lowering incremental to standard care with moderate-intensity statins or intensive lifestyle interventions was simulated starting when young adult LDL-C was either ≥160 mg/dL or ≥130 mg/dL.
They found that approximately 27% of young adults who are free of ASCVD have LDL-C ≥130 mg/dL, and 9% have LDL-C of ≥160 mg/dL.
Their model projected that treating adults younger than 40 with statins or lifestyle interventions would prevent lifetime ASCVD events and increase quality-adjusted life years (QALYs) compared with standard care, which would begin treatment at age 40.
Incremental cost-effectiveness ratios (ICERs) were $31,000/QALY for statin treatment in young adult men with LDL-C ≥130 mg/dL, and $106,000/QALY for statin treatment in young women with LDL-C ≥130 mg/dL.
Intensive lifestyle intervention was more costly and less effective than statin therapy.
“We are straining to find these young adults with very high cholesterol,” Dr. Moran noted. “A lot of young adults don’t even see a doctor. This is an argument for engaging them in their health care and getting them involved in some basic screening. Atherosclerosis is a long-term process that starts in childhood for a lot of people.”
More innovative approaches may be needed, because the traditional health care system is not doing a good job of reaching young adults, he added. “Many of them may not have adequate health insurance. They need health care in nontraditional ways; convenience is really important for them. Perhaps part of the solution here is to think about ways of reaching this particular group that is not engaged with health care generally.”
Time to relax the age 40 threshold
The U.S. Preventive Services Task Force and the American College of Cardiology/American Heart Association should emphasize lifetime risk of elevated cholesterol, Paul A. Heidenreich, MD, MS, Stanford University School of Medicine, California, and colleagues write in an accompanying editorial.
“In addition to calculating 10-year risk, we should calculate years of life lost (or QALYs lost) from unhealthy LDL-C levels, and both lifestyle and pharmacologic treatment should be considered to treat high LDL-C in adults regardless of age. We also need to communicate that the mantra ‘lower is better’ applies not only to a single measurement but to lifetime exposure to LDL-C,” the editorialists write.
“I think treatment should be earlier than age 40,” Dr. Heidenreich said in an interview.
“Part of the reason that 40 was chosen as a threshold was because everyone looked at 10-year, or even 20-year risk, and thought there was no reason to worry until you get older. It’s interesting that we never accepted that with high blood pressure. But more and more, we are learning that it is a lifelong process,” he said.
“Statins are getting less and less expensive, and their safety is more and more established with every decade that goes by. I definitely agree with this paper that it would actually make sense to be starting much earlier for those with elevated CVD risk from their high cholesterol.”
The study was supported by the U.S. National Heart, Lung, and Blood Institute (NHLBI), the Medical Research Council, Swindon, U.K. Dr. Moran and Dr. Heidenreich have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Antithrombotic therapy not warranted in COVID-19 outpatients
Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.
Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.
“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”
The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.
The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.
The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.
Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.
The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.
The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.
The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.
The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.
The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.
Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.
The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.
No major bleeding events were reported.
The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.
Safety and efficacy results were similar in all randomly assigned patients.
The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.
“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”
“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.
Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
Robust evidence
“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.
“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.
The ACTIV-4B trial has immediate implications for clinical practice, he added.
“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”
ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.
“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.
The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.
Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.
“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”
The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.
The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.
The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.
Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.
The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.
The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.
The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.
The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.
The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.
Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.
The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.
No major bleeding events were reported.
The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.
Safety and efficacy results were similar in all randomly assigned patients.
The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.
“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”
“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.
Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
Robust evidence
“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.
“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.
The ACTIV-4B trial has immediate implications for clinical practice, he added.
“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”
ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.
“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.
The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
Antithrombotic therapy in clinically stable, nonhospitalized COVID-19 patients does not offer protection against adverse cardiovascular or pulmonary events, new randomized clinical trial results suggest.
Antithrombotic therapy has proven useful in acutely ill inpatients with COVID-19, but in this study, treatment with aspirin or apixaban (Eliquis) did not reduce the rate of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary causes in patients ill with COVID-19 but who were not hospitalized.
“Among symptomatic, clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome,” the authors conclude. “However, the study was terminated after enrollment of 9% of participants because of a primary event rate lower than anticipated.”
The study, which was led by Jean M. Connors, MD, Brigham and Women’s Hospital, Boston, was published online October 11 in JAMA.
The ACTIV-4B Outpatient Thrombosis Prevention Trial was a randomized, adaptive, double-blind, placebo-controlled trial that sought to compare anticoagulant and antiplatelet therapy among 7,000 symptomatic but clinically stable outpatients with COVID-19.
The trial was conducted at 52 sites in the U.S. between Sept. 2020 and June 2021, with final follow-up this past August 5, and involved minimal face-to-face interactions with study participants.
Patients were randomized in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164 patients), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days.
The primary endpoint was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause.
The trial was terminated early this past June by the independent data monitoring committee because of lower than anticipated event rates. At the time, just 657 symptomatic outpatients with COVID-19 had been enrolled.
The median age of the study participants was 54 years (Interquartile Range [IQR] 46-59); 59% were women.
The median time from diagnosis to randomization was 7 days, and the median time from randomization to initiation of study medications was 3 days.
The trial’s primary efficacy and safety analyses were restricted to patients who received at least one dose of trial medication, for a final number of 558 patients.
Among these patients, the primary endpoint occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5 mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group.
The researchers found that the absolute risk reductions compared with placebo for the primary outcome were 0.0% (95% confidence interval not calculable) in the aspirin group, 0.7% (95% confidence interval, -2.1% to 4.1%) in the prophylactic-dose apixaban group, and 1.4% (95% CI, -1.5% to 5%) in the therapeutic-dose apixaban group.
No major bleeding events were reported.
The absolute risk differences compared with placebo for clinically relevant nonmajor bleeding events were 2% (95% CI, -2.7% to 6.8%) in the aspirin group, 4.5% (95% CI, -0.7% to 10.2%) in the prophylactic-dose apixaban group, and 6.9% (95% CI, 1.4% to 12.9%) in the therapeutic-dose apixaban group.
Safety and efficacy results were similar in all randomly assigned patients.
The researchers speculated that a combination of two demographic shifts over time may have led to the lower than anticipated rate of events in ACTIV-4B.
“First, the threshold for hospital admission has markedly declined since the beginning of the pandemic, such that hospitalization is no longer limited almost exclusively to those with severe pulmonary distress likely to require mechanical ventilation,” they write. “As a result, the severity of illness among individuals with COVID-19 and destined for outpatient care has declined.”
“Second, at least within the U.S., where the trial was conducted, individuals currently being infected with SARS-CoV-2 tend to be younger and have fewer comorbidities when compared with individuals with incident infection at the onset of the pandemic,” they add.
Further, COVID-19 testing was quite limited early in the pandemic, they note, “and it is possible that the anticipated event rates based on data from registries available at that time were overestimated because the denominator (that is, the number of infected individuals overall) was essentially unknown.”
Robust evidence
“The ACTIV-4B trial is the first randomized trial to generate robust evidence about the effects of antithrombotic therapy in outpatients with COVID-19,” Otavio Berwanger, MD, PhD, director of the Academic Research Organization, Hospital Israelita Albert Einstein, Sao Paulo-SP, Brazil, told this news organization.
“It should be noted that this was a well-designed trial with low risk of bias. On the other hand, the main limitation is the low number of events and, consequently, the limited statistical power,” said Dr. Berwanger, who wrote an accompanying editorial.
The ACTIV-4B trial has immediate implications for clinical practice, he added.
“In this sense, considering the neutral results for major cardiopulmonary outcomes, the use of aspirin or apixaban for the management of outpatients with COVID-19 should not be recommended.”
ACTIV-4B also provides useful information for the steering committees of other ongoing trials of antithrombotic therapy for patients with COVID-19 who are not hospitalized, Dr. Berwanger added.
“In this sense, probably issues like statistical power, outcome choices, recruitment feasibility, and even futility would need to be revisited. And finally, lessons learned from the implementation of an innovative, pragmatic, and decentralized trial design represent an important legacy for future trials in cardiovascular diseases and other common conditions,” he said.
The study was funded by the National Institutes of Health, and the National Heart, Lung, and Blood Institute. Dr. Connors reports financial relationships with Bristol-Myers Squibb, Pfizer, Abbott, Alnylam, Takeda, Roche, and Sanofi. Dr. Berwanger reports financial relationships with AstraZeneca, Amgen, Servier, Bristol-Myers Squibb, Bayer, Novartis, Pfizer, and Boehringer Ingelheim.
A version of this article first appeared on Medscape.com.
D-dimer unreliable for ruling out pulmonary embolism in COVID-19
The plasma D-dimer assay has been used, along with clinical prediction scores, to rule out pulmonary embolism (PE) in critically ill patients for decades, but a new study suggests it may not be the right test to use in hospitalized COVID-19 patients.
The results showed that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater, the cutoff point for the diagnosis.
“If using D-dimer to exclude patients with PE, the increased values we found among 92.3% of patients suggest that this assay would be less useful than in the populations in which it was originally validated, among which a minority of patients had increased D-dimer values,” the authors write. “Setting higher D-dimer thresholds was associated with improved specificity at the cost of an increased false-negative rate that could be associated with an unacceptable patient safety risk.”
The inclusion of patients with D-dimer and computed tomography pulmonary angiography (CTPA) was necessary to estimate diagnostic performance, they note, but “this may have introduced selection bias by excluding patients unable to undergo CTPA.”
“Nonetheless, given the high pretest probability of PE and low specificity observed in this and other studies, these results suggest that use of D-dimer levels to exclude PE among patients hospitalized with COVID-19 may be inappropriate and have limited clinical utility,” they conclude.
Led by Constantine N. Logothetis, MD, from Morsani College of Medicine, University of South Florida, Tampa, the study was published online Oct. 8 as a Research Letter in JAMA Network Open.
Uncertain utility
The authors note that the availability of D-dimer samples routinely collected from hospitalized COVID-19 patients – as well as the heterogeneity of early, smaller studies – generated uncertainty about the utility of this assay.
This uncertainty prompted them to test the diagnostic accuracy of the D-dimer assay among a sample of 1,541 patients who were hospitalized with COVID-19 at their institution between January 2020 and February 2021 for a possible PE.
They compared plasma D-dimer concentrations with CTPA, the criterion standard for diagnosing PE, in 287 of those patients.
Overall, 118 patients (41.1%) required care in the ICU, and 27 patients (9.4%) died during hospitalization.
The investigators looked at the ability of plasma D-dimer levels collected on the same day as CTPA to diagnose PE.
Thirty-seven patients (12.9%) had radiographic evidence of PE, and 250 patients (87.1%) did not.
Overall, the vast majority of patients (92.3%; n = 265 patients) had plasma D-dimer levels of 0.05 mcg/mL or more, including all patients with PE and 225 of 250 patients without PE (91.2%).
The median D-dimer values were 1.0 mcg/mL for 250 patients without PE and 6.1 mcg/mL for 37 patients with PE.
D-dimer values ranged from 0.2 mcg/mL to 128 mcg/mL among patients without PE, and from 0.5 mcg/mL to more than 10,000 mcg/mL among patients with PE. Patients without PE had statistically significantly decreased mean D-dimer values (8.7 mcg/mL vs. 1.2 mcg/mL; P < .001).
A D-dimer concentration of 0.05 mcg/mL was associated with a sensitivity of 100%, specificity of 8.8%, negative predictive value (NPV) of 100%, positive predictive value (PPV) of 13.9%, and a negative likelihood ratio (NLR) of less than 0.1.
The age-adjusted threshold was associated with a sensitivity of 94.6%, specificity of 22.8%, NPV of 96.6%, PPV of 13.9%, and NLR of 0.24.
The authors note that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater.
D-dimer in VTE may not extrapolate to COVID-19
“The D-dimer test, which is a measure of circulating byproducts of blood clot dissolution, has long been incorporated into diagnostic algorithms for venous thromboembolic [VTE] disease, including deep vein thrombosis and pulmonary embolism. It is uncertain whether this diagnostic use of D-dimer testing can be extrapolated to the context of COVID-19 – an illness we now understand to be associated itself with intravascular thrombosis and fibrinolysis,” Matthew Tomey, MD, a cardiologist at Mount Sinai Morningside, New York, said in an interview.
“The authors of this study sought to evaluate the test characteristics of the D-dimer assay for diagnosis of pulmonary embolism in a consecutive series of 287 hospitalized patients with COVID-19 who underwent computed tomography pulmonary angiography (CTPA). This was a selected group of patients representing less than 20% of the 1,541 patients screened. Exclusion of data on the more than 80% of screened patients who did not undergo CTPA is a significant limitation of the study,” Dr. Tomey said.
“In the highly selected, small cohort studied, representing a group of patients at high pretest probability of pulmonary embolism, there was no patient with pulmonary embolism who had a D-dimer value less than 0.5 mcg/mL. Yet broad ranges of D-dimer values were observed in COVID-19 patients with (0.5 to >10,000 mcg/mL) and without (0.2 to 128 mcg/mL) pulmonary embolism,” he added.
Based on the presented data, it is likely true that very low levels of D-dimer decrease the likelihood of finding a pulmonary embolus on a CTPA, if it is performed, Dr. Tomey noted.
“Yet the data confirm that a wide range of D-dimer values can be observed in COVID-19 patients with or without pulmonary embolism. It is not clear at this time that D-dimer levels should be used as gatekeepers to diagnostic imaging studies such as CTPA when pretest suspicion of pulmonary embolism is high,” he said.
“This issue becomes relevant as we consider evolving data on use of anticoagulation in treatment of hospitalized patients with COVID-19. We learned this year that in critically ill patients hospitalized with COVID-19, routine therapeutic anticoagulation (with heparin) was not beneficial and potentially harmful when compared with usual thromboprophylaxis,” he concluded.
“As we strive to balance competing risks of bleeding and thrombosis, accurate diagnosis of pulmonary embolism is important to guide decision-making about therapeutic anticoagulation, including in COVID-19.”
Dr. Logothetis and Dr. Tomey have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The plasma D-dimer assay has been used, along with clinical prediction scores, to rule out pulmonary embolism (PE) in critically ill patients for decades, but a new study suggests it may not be the right test to use in hospitalized COVID-19 patients.
The results showed that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater, the cutoff point for the diagnosis.
“If using D-dimer to exclude patients with PE, the increased values we found among 92.3% of patients suggest that this assay would be less useful than in the populations in which it was originally validated, among which a minority of patients had increased D-dimer values,” the authors write. “Setting higher D-dimer thresholds was associated with improved specificity at the cost of an increased false-negative rate that could be associated with an unacceptable patient safety risk.”
The inclusion of patients with D-dimer and computed tomography pulmonary angiography (CTPA) was necessary to estimate diagnostic performance, they note, but “this may have introduced selection bias by excluding patients unable to undergo CTPA.”
“Nonetheless, given the high pretest probability of PE and low specificity observed in this and other studies, these results suggest that use of D-dimer levels to exclude PE among patients hospitalized with COVID-19 may be inappropriate and have limited clinical utility,” they conclude.
Led by Constantine N. Logothetis, MD, from Morsani College of Medicine, University of South Florida, Tampa, the study was published online Oct. 8 as a Research Letter in JAMA Network Open.
Uncertain utility
The authors note that the availability of D-dimer samples routinely collected from hospitalized COVID-19 patients – as well as the heterogeneity of early, smaller studies – generated uncertainty about the utility of this assay.
This uncertainty prompted them to test the diagnostic accuracy of the D-dimer assay among a sample of 1,541 patients who were hospitalized with COVID-19 at their institution between January 2020 and February 2021 for a possible PE.
They compared plasma D-dimer concentrations with CTPA, the criterion standard for diagnosing PE, in 287 of those patients.
Overall, 118 patients (41.1%) required care in the ICU, and 27 patients (9.4%) died during hospitalization.
The investigators looked at the ability of plasma D-dimer levels collected on the same day as CTPA to diagnose PE.
Thirty-seven patients (12.9%) had radiographic evidence of PE, and 250 patients (87.1%) did not.
Overall, the vast majority of patients (92.3%; n = 265 patients) had plasma D-dimer levels of 0.05 mcg/mL or more, including all patients with PE and 225 of 250 patients without PE (91.2%).
The median D-dimer values were 1.0 mcg/mL for 250 patients without PE and 6.1 mcg/mL for 37 patients with PE.
D-dimer values ranged from 0.2 mcg/mL to 128 mcg/mL among patients without PE, and from 0.5 mcg/mL to more than 10,000 mcg/mL among patients with PE. Patients without PE had statistically significantly decreased mean D-dimer values (8.7 mcg/mL vs. 1.2 mcg/mL; P < .001).
A D-dimer concentration of 0.05 mcg/mL was associated with a sensitivity of 100%, specificity of 8.8%, negative predictive value (NPV) of 100%, positive predictive value (PPV) of 13.9%, and a negative likelihood ratio (NLR) of less than 0.1.
The age-adjusted threshold was associated with a sensitivity of 94.6%, specificity of 22.8%, NPV of 96.6%, PPV of 13.9%, and NLR of 0.24.
The authors note that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater.
D-dimer in VTE may not extrapolate to COVID-19
“The D-dimer test, which is a measure of circulating byproducts of blood clot dissolution, has long been incorporated into diagnostic algorithms for venous thromboembolic [VTE] disease, including deep vein thrombosis and pulmonary embolism. It is uncertain whether this diagnostic use of D-dimer testing can be extrapolated to the context of COVID-19 – an illness we now understand to be associated itself with intravascular thrombosis and fibrinolysis,” Matthew Tomey, MD, a cardiologist at Mount Sinai Morningside, New York, said in an interview.
“The authors of this study sought to evaluate the test characteristics of the D-dimer assay for diagnosis of pulmonary embolism in a consecutive series of 287 hospitalized patients with COVID-19 who underwent computed tomography pulmonary angiography (CTPA). This was a selected group of patients representing less than 20% of the 1,541 patients screened. Exclusion of data on the more than 80% of screened patients who did not undergo CTPA is a significant limitation of the study,” Dr. Tomey said.
“In the highly selected, small cohort studied, representing a group of patients at high pretest probability of pulmonary embolism, there was no patient with pulmonary embolism who had a D-dimer value less than 0.5 mcg/mL. Yet broad ranges of D-dimer values were observed in COVID-19 patients with (0.5 to >10,000 mcg/mL) and without (0.2 to 128 mcg/mL) pulmonary embolism,” he added.
Based on the presented data, it is likely true that very low levels of D-dimer decrease the likelihood of finding a pulmonary embolus on a CTPA, if it is performed, Dr. Tomey noted.
“Yet the data confirm that a wide range of D-dimer values can be observed in COVID-19 patients with or without pulmonary embolism. It is not clear at this time that D-dimer levels should be used as gatekeepers to diagnostic imaging studies such as CTPA when pretest suspicion of pulmonary embolism is high,” he said.
“This issue becomes relevant as we consider evolving data on use of anticoagulation in treatment of hospitalized patients with COVID-19. We learned this year that in critically ill patients hospitalized with COVID-19, routine therapeutic anticoagulation (with heparin) was not beneficial and potentially harmful when compared with usual thromboprophylaxis,” he concluded.
“As we strive to balance competing risks of bleeding and thrombosis, accurate diagnosis of pulmonary embolism is important to guide decision-making about therapeutic anticoagulation, including in COVID-19.”
Dr. Logothetis and Dr. Tomey have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The plasma D-dimer assay has been used, along with clinical prediction scores, to rule out pulmonary embolism (PE) in critically ill patients for decades, but a new study suggests it may not be the right test to use in hospitalized COVID-19 patients.
The results showed that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater, the cutoff point for the diagnosis.
“If using D-dimer to exclude patients with PE, the increased values we found among 92.3% of patients suggest that this assay would be less useful than in the populations in which it was originally validated, among which a minority of patients had increased D-dimer values,” the authors write. “Setting higher D-dimer thresholds was associated with improved specificity at the cost of an increased false-negative rate that could be associated with an unacceptable patient safety risk.”
The inclusion of patients with D-dimer and computed tomography pulmonary angiography (CTPA) was necessary to estimate diagnostic performance, they note, but “this may have introduced selection bias by excluding patients unable to undergo CTPA.”
“Nonetheless, given the high pretest probability of PE and low specificity observed in this and other studies, these results suggest that use of D-dimer levels to exclude PE among patients hospitalized with COVID-19 may be inappropriate and have limited clinical utility,” they conclude.
Led by Constantine N. Logothetis, MD, from Morsani College of Medicine, University of South Florida, Tampa, the study was published online Oct. 8 as a Research Letter in JAMA Network Open.
Uncertain utility
The authors note that the availability of D-dimer samples routinely collected from hospitalized COVID-19 patients – as well as the heterogeneity of early, smaller studies – generated uncertainty about the utility of this assay.
This uncertainty prompted them to test the diagnostic accuracy of the D-dimer assay among a sample of 1,541 patients who were hospitalized with COVID-19 at their institution between January 2020 and February 2021 for a possible PE.
They compared plasma D-dimer concentrations with CTPA, the criterion standard for diagnosing PE, in 287 of those patients.
Overall, 118 patients (41.1%) required care in the ICU, and 27 patients (9.4%) died during hospitalization.
The investigators looked at the ability of plasma D-dimer levels collected on the same day as CTPA to diagnose PE.
Thirty-seven patients (12.9%) had radiographic evidence of PE, and 250 patients (87.1%) did not.
Overall, the vast majority of patients (92.3%; n = 265 patients) had plasma D-dimer levels of 0.05 mcg/mL or more, including all patients with PE and 225 of 250 patients without PE (91.2%).
The median D-dimer values were 1.0 mcg/mL for 250 patients without PE and 6.1 mcg/mL for 37 patients with PE.
D-dimer values ranged from 0.2 mcg/mL to 128 mcg/mL among patients without PE, and from 0.5 mcg/mL to more than 10,000 mcg/mL among patients with PE. Patients without PE had statistically significantly decreased mean D-dimer values (8.7 mcg/mL vs. 1.2 mcg/mL; P < .001).
A D-dimer concentration of 0.05 mcg/mL was associated with a sensitivity of 100%, specificity of 8.8%, negative predictive value (NPV) of 100%, positive predictive value (PPV) of 13.9%, and a negative likelihood ratio (NLR) of less than 0.1.
The age-adjusted threshold was associated with a sensitivity of 94.6%, specificity of 22.8%, NPV of 96.6%, PPV of 13.9%, and NLR of 0.24.
The authors note that all hospitalized patients with COVID-19 and radiographic evidence of PE had plasma D-dimer levels of 0.05 mcg/mL or greater.
D-dimer in VTE may not extrapolate to COVID-19
“The D-dimer test, which is a measure of circulating byproducts of blood clot dissolution, has long been incorporated into diagnostic algorithms for venous thromboembolic [VTE] disease, including deep vein thrombosis and pulmonary embolism. It is uncertain whether this diagnostic use of D-dimer testing can be extrapolated to the context of COVID-19 – an illness we now understand to be associated itself with intravascular thrombosis and fibrinolysis,” Matthew Tomey, MD, a cardiologist at Mount Sinai Morningside, New York, said in an interview.
“The authors of this study sought to evaluate the test characteristics of the D-dimer assay for diagnosis of pulmonary embolism in a consecutive series of 287 hospitalized patients with COVID-19 who underwent computed tomography pulmonary angiography (CTPA). This was a selected group of patients representing less than 20% of the 1,541 patients screened. Exclusion of data on the more than 80% of screened patients who did not undergo CTPA is a significant limitation of the study,” Dr. Tomey said.
“In the highly selected, small cohort studied, representing a group of patients at high pretest probability of pulmonary embolism, there was no patient with pulmonary embolism who had a D-dimer value less than 0.5 mcg/mL. Yet broad ranges of D-dimer values were observed in COVID-19 patients with (0.5 to >10,000 mcg/mL) and without (0.2 to 128 mcg/mL) pulmonary embolism,” he added.
Based on the presented data, it is likely true that very low levels of D-dimer decrease the likelihood of finding a pulmonary embolus on a CTPA, if it is performed, Dr. Tomey noted.
“Yet the data confirm that a wide range of D-dimer values can be observed in COVID-19 patients with or without pulmonary embolism. It is not clear at this time that D-dimer levels should be used as gatekeepers to diagnostic imaging studies such as CTPA when pretest suspicion of pulmonary embolism is high,” he said.
“This issue becomes relevant as we consider evolving data on use of anticoagulation in treatment of hospitalized patients with COVID-19. We learned this year that in critically ill patients hospitalized with COVID-19, routine therapeutic anticoagulation (with heparin) was not beneficial and potentially harmful when compared with usual thromboprophylaxis,” he concluded.
“As we strive to balance competing risks of bleeding and thrombosis, accurate diagnosis of pulmonary embolism is important to guide decision-making about therapeutic anticoagulation, including in COVID-19.”
Dr. Logothetis and Dr. Tomey have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Circulating post-STEMI ketones elevated, hints at treatment role
Circulating ketone bodies (KBs) are substantially elevated at presentation and 24 hours after ST-segment elevation myocardial infarction (STEMI), according to new research.
The study also showed that greater KB levels measured after 24 hours of reperfusion were associated with larger infarct size and reduced left ventricular ejection fraction (LVEF).
The findings suggest a potential role for ketone metabolism in response to myocardial ischemia, conclude researchers in their report, published in the October 5 issue of the Journal of the American College of Cardiology.
“Ketones serve as an alternative source of energy for the heart,” lead author Marie-Sophie L.Y. de Koning, MD, University Medical Center Groningen, the Netherlands, told this news organization.
“These results might suggest that ketone bodies may be an important fuel for the heart after myocardial ischemia.” The role of KBs in heart failure has been previously studied, but their role in myocardial infarction has not, Dr. De Koning said.
“In heart failure, metabolic changes occur that cause the heart to increasingly rely on ketone bodies as an important energy source. Accordingly, concentrations of circulating ketone bodies are elevated and higher concentrations have been linked with more severe heart failure,” she said.
”This might suggest that upregulation of ketone metabolism is a universal cardiac response to stress,” Dr. De Koning added. “But the role of ketone bodies in myocardial infarction remained largely unknown, and this triggered us to investigate circulating ketone bodies in patients presenting with STEMI.”
She and her team measured circulating KBs in archived plasma samples from 369 participants in the randomized GIPS-III trial. The study had primarily looked at the effect of 4 months of metformin therapy, compared with placebo, on LVEF in nondiabetic patients with a first STEMI.
Blood samples had been taken at baseline before percutaneous coronary intervention (PCI), at 24 hours after reperfusion, and at 4 months.
The current study investigated longitudinal post-STEMI changes in the circulating KBs beta-hydroxybutyrate, acetoacetate, and acetone. It also looked at associations of KBs with infarct size and LVEF, both of which were measured with cardiac magnetic resonance (CMR) imaging 4 months after STEMI.
Circulating KB levels were three times higher at STEMI presentation than at 4 months. At presentation, the median total KB level was 520 μmol/L. It was still higher 24 hours after reperfusion than at 4 months (206 vs. 166 μmol/L; P < .001).
The 24-hour KB elevations were independently and positively associated with larger infarct size (P = .016) and lower LVEF (P = .012), the group reports.
“Our results indicate a possible role for ketone bodies during myocardial infarction,” Dr. De Koning said.
The KB elevations were probably followed by “an increase in cardiac ketone body metabolism, in order to fuel the heart that is energetically depleted.”
But the study didn’t explore cardiac KB consumption, Dr. De Koning cautioned, adding that the next steps in this research should be to investigate post-STEMI cardiac ketone metabolism and its pathophysiologic mechanisms. “This may facilitate future trials to study therapeutic effects of ketone body supplementation during or after STEMI.”
The current findings “form an essential basis for our understanding of the role of KBs in ischemia/reperfusion,” write Salva R. Yurista, MD, PhD, and colleagues, Massachusetts General Hospital and Harvard Medical School, Boston, in an accompanying editorial.
“Although the appeal of enhancing KBs as a therapeutic approach is understandable, additional rigorous preclinical and clinical studies will be required to test this therapeutic hypothesis and determine the mechanisms contributing to any benefits observed,” they note.
”Exposure to cardiac stress, such as ischemia, infarction, or heart failure, will stimulate the release of neurohormones, pro-inflammatory cytokines, and natriuretic peptides, which may play roles in stimulating ketogenesis or the production of ketone bodies,” Dr. Yurista told this news organization.
The increased circulating ketone concentrations and myocardial ketone oxidation that were associated with poor functional outcomes have been reported in other clinical contexts, including heart failure with reduced ejection fraction, heart failure with preserved cardiac function, diabetic cardiomyopathy, and arrhythmogenic cardiomyopathy, he said.
Dr. Yurista agrees that KBs could have therapeutic merit.
“Circulating ketone concentrations determine the contribution of ketones to the cardiac diet,” he said. “Thus, increasing cardiac delivery of ketone bodies through supplementation or other means to the heart undergoing stress, including STEMI and heart failure, could have therapeutic potential.”
The GIPS-III trial was supported by the Netherlands Organization for Health Research and Development (ZonMw). Neither Dr. De Koning nor the other authors report relevant financial relationships. Dr. Yurista and the other editorialists report no relevant relationships.
A version of this article first appeared on Medscape.com.
Circulating ketone bodies (KBs) are substantially elevated at presentation and 24 hours after ST-segment elevation myocardial infarction (STEMI), according to new research.
The study also showed that greater KB levels measured after 24 hours of reperfusion were associated with larger infarct size and reduced left ventricular ejection fraction (LVEF).
The findings suggest a potential role for ketone metabolism in response to myocardial ischemia, conclude researchers in their report, published in the October 5 issue of the Journal of the American College of Cardiology.
“Ketones serve as an alternative source of energy for the heart,” lead author Marie-Sophie L.Y. de Koning, MD, University Medical Center Groningen, the Netherlands, told this news organization.
“These results might suggest that ketone bodies may be an important fuel for the heart after myocardial ischemia.” The role of KBs in heart failure has been previously studied, but their role in myocardial infarction has not, Dr. De Koning said.
“In heart failure, metabolic changes occur that cause the heart to increasingly rely on ketone bodies as an important energy source. Accordingly, concentrations of circulating ketone bodies are elevated and higher concentrations have been linked with more severe heart failure,” she said.
”This might suggest that upregulation of ketone metabolism is a universal cardiac response to stress,” Dr. De Koning added. “But the role of ketone bodies in myocardial infarction remained largely unknown, and this triggered us to investigate circulating ketone bodies in patients presenting with STEMI.”
She and her team measured circulating KBs in archived plasma samples from 369 participants in the randomized GIPS-III trial. The study had primarily looked at the effect of 4 months of metformin therapy, compared with placebo, on LVEF in nondiabetic patients with a first STEMI.
Blood samples had been taken at baseline before percutaneous coronary intervention (PCI), at 24 hours after reperfusion, and at 4 months.
The current study investigated longitudinal post-STEMI changes in the circulating KBs beta-hydroxybutyrate, acetoacetate, and acetone. It also looked at associations of KBs with infarct size and LVEF, both of which were measured with cardiac magnetic resonance (CMR) imaging 4 months after STEMI.
Circulating KB levels were three times higher at STEMI presentation than at 4 months. At presentation, the median total KB level was 520 μmol/L. It was still higher 24 hours after reperfusion than at 4 months (206 vs. 166 μmol/L; P < .001).
The 24-hour KB elevations were independently and positively associated with larger infarct size (P = .016) and lower LVEF (P = .012), the group reports.
“Our results indicate a possible role for ketone bodies during myocardial infarction,” Dr. De Koning said.
The KB elevations were probably followed by “an increase in cardiac ketone body metabolism, in order to fuel the heart that is energetically depleted.”
But the study didn’t explore cardiac KB consumption, Dr. De Koning cautioned, adding that the next steps in this research should be to investigate post-STEMI cardiac ketone metabolism and its pathophysiologic mechanisms. “This may facilitate future trials to study therapeutic effects of ketone body supplementation during or after STEMI.”
The current findings “form an essential basis for our understanding of the role of KBs in ischemia/reperfusion,” write Salva R. Yurista, MD, PhD, and colleagues, Massachusetts General Hospital and Harvard Medical School, Boston, in an accompanying editorial.
“Although the appeal of enhancing KBs as a therapeutic approach is understandable, additional rigorous preclinical and clinical studies will be required to test this therapeutic hypothesis and determine the mechanisms contributing to any benefits observed,” they note.
”Exposure to cardiac stress, such as ischemia, infarction, or heart failure, will stimulate the release of neurohormones, pro-inflammatory cytokines, and natriuretic peptides, which may play roles in stimulating ketogenesis or the production of ketone bodies,” Dr. Yurista told this news organization.
The increased circulating ketone concentrations and myocardial ketone oxidation that were associated with poor functional outcomes have been reported in other clinical contexts, including heart failure with reduced ejection fraction, heart failure with preserved cardiac function, diabetic cardiomyopathy, and arrhythmogenic cardiomyopathy, he said.
Dr. Yurista agrees that KBs could have therapeutic merit.
“Circulating ketone concentrations determine the contribution of ketones to the cardiac diet,” he said. “Thus, increasing cardiac delivery of ketone bodies through supplementation or other means to the heart undergoing stress, including STEMI and heart failure, could have therapeutic potential.”
The GIPS-III trial was supported by the Netherlands Organization for Health Research and Development (ZonMw). Neither Dr. De Koning nor the other authors report relevant financial relationships. Dr. Yurista and the other editorialists report no relevant relationships.
A version of this article first appeared on Medscape.com.
Circulating ketone bodies (KBs) are substantially elevated at presentation and 24 hours after ST-segment elevation myocardial infarction (STEMI), according to new research.
The study also showed that greater KB levels measured after 24 hours of reperfusion were associated with larger infarct size and reduced left ventricular ejection fraction (LVEF).
The findings suggest a potential role for ketone metabolism in response to myocardial ischemia, conclude researchers in their report, published in the October 5 issue of the Journal of the American College of Cardiology.
“Ketones serve as an alternative source of energy for the heart,” lead author Marie-Sophie L.Y. de Koning, MD, University Medical Center Groningen, the Netherlands, told this news organization.
“These results might suggest that ketone bodies may be an important fuel for the heart after myocardial ischemia.” The role of KBs in heart failure has been previously studied, but their role in myocardial infarction has not, Dr. De Koning said.
“In heart failure, metabolic changes occur that cause the heart to increasingly rely on ketone bodies as an important energy source. Accordingly, concentrations of circulating ketone bodies are elevated and higher concentrations have been linked with more severe heart failure,” she said.
”This might suggest that upregulation of ketone metabolism is a universal cardiac response to stress,” Dr. De Koning added. “But the role of ketone bodies in myocardial infarction remained largely unknown, and this triggered us to investigate circulating ketone bodies in patients presenting with STEMI.”
She and her team measured circulating KBs in archived plasma samples from 369 participants in the randomized GIPS-III trial. The study had primarily looked at the effect of 4 months of metformin therapy, compared with placebo, on LVEF in nondiabetic patients with a first STEMI.
Blood samples had been taken at baseline before percutaneous coronary intervention (PCI), at 24 hours after reperfusion, and at 4 months.
The current study investigated longitudinal post-STEMI changes in the circulating KBs beta-hydroxybutyrate, acetoacetate, and acetone. It also looked at associations of KBs with infarct size and LVEF, both of which were measured with cardiac magnetic resonance (CMR) imaging 4 months after STEMI.
Circulating KB levels were three times higher at STEMI presentation than at 4 months. At presentation, the median total KB level was 520 μmol/L. It was still higher 24 hours after reperfusion than at 4 months (206 vs. 166 μmol/L; P < .001).
The 24-hour KB elevations were independently and positively associated with larger infarct size (P = .016) and lower LVEF (P = .012), the group reports.
“Our results indicate a possible role for ketone bodies during myocardial infarction,” Dr. De Koning said.
The KB elevations were probably followed by “an increase in cardiac ketone body metabolism, in order to fuel the heart that is energetically depleted.”
But the study didn’t explore cardiac KB consumption, Dr. De Koning cautioned, adding that the next steps in this research should be to investigate post-STEMI cardiac ketone metabolism and its pathophysiologic mechanisms. “This may facilitate future trials to study therapeutic effects of ketone body supplementation during or after STEMI.”
The current findings “form an essential basis for our understanding of the role of KBs in ischemia/reperfusion,” write Salva R. Yurista, MD, PhD, and colleagues, Massachusetts General Hospital and Harvard Medical School, Boston, in an accompanying editorial.
“Although the appeal of enhancing KBs as a therapeutic approach is understandable, additional rigorous preclinical and clinical studies will be required to test this therapeutic hypothesis and determine the mechanisms contributing to any benefits observed,” they note.
”Exposure to cardiac stress, such as ischemia, infarction, or heart failure, will stimulate the release of neurohormones, pro-inflammatory cytokines, and natriuretic peptides, which may play roles in stimulating ketogenesis or the production of ketone bodies,” Dr. Yurista told this news organization.
The increased circulating ketone concentrations and myocardial ketone oxidation that were associated with poor functional outcomes have been reported in other clinical contexts, including heart failure with reduced ejection fraction, heart failure with preserved cardiac function, diabetic cardiomyopathy, and arrhythmogenic cardiomyopathy, he said.
Dr. Yurista agrees that KBs could have therapeutic merit.
“Circulating ketone concentrations determine the contribution of ketones to the cardiac diet,” he said. “Thus, increasing cardiac delivery of ketone bodies through supplementation or other means to the heart undergoing stress, including STEMI and heart failure, could have therapeutic potential.”
The GIPS-III trial was supported by the Netherlands Organization for Health Research and Development (ZonMw). Neither Dr. De Koning nor the other authors report relevant financial relationships. Dr. Yurista and the other editorialists report no relevant relationships.
A version of this article first appeared on Medscape.com.