Cardiology

Among professional football players, the concussion burden during years of active play is associated with post-career high blood pressure, a new study suggests.

Among more than 4,000 participants, 37% had hypertension at a median of 24 years post career and reported a median concussion symptom score (CSS) of 23 on a scale of 0 to 130.

“We have long seen an incompletely explained link between football participation and later-life cardiovascular disease,” Aaron L. Baggish, MD, of Massachusetts Hospital and Harvard Medical School, Boston, told this news organization.

“This study tested [whether] concussion burden during years of active play would be a determinant of later-life hypertension, the most common cause of cardiovascular disease, and indeed found this relationship to be a strong one.”

The study was published online in Circulation.
 

Link to cognitive decline?

Dr. Baggish and colleagues recruited former professional American-style football (ASF) players to participate in a survey administered by the Football Players Health Study at Harvard University.

Concussion burden was quantified with respect to the occurrence and severity of common concussion symptoms – e.g., headaches, nausea, dizziness, confusion, loss of consciousness (LOC), disorientation, and feeling unsteady on one’s feet – over years of active participation.

Prevalent hypertension was determined either by the participants’ previously receiving from a clinician a recommendation for medication for “high blood pressure” or by the participants’ taking such medication at the time of survey completion. Diabetes status was determined by the participants’ receiving a prior recommendation for or prescription for “diabetes or high blood sugar” medication.

Of 15,070 invited to participate in the study, 4,168 did so. The mean age of the participants was 51.8 years; 39.4% were Black; the mean body mass index was 31.3; and 33.9% were linemen. Participants played for a mean of 6.9 seasons and were surveyed at a median 24.1 years post ASF career completion. The median CSS was 23.

A total of 1,542 participants (37.3%) had hypertension, and 8.8% had diabetes.

After adjustment for established hypertension risk factors, including smoking, race, diabetes, age, and BMI, there was a graded association between CSS category and odds of later-life hypertension and between high CSS exposure and prevalent hypertension.

Results persisted when LOC, a single highly specific severe concussion symptom, was used in isolation as a surrogate for CSS, the investigators noted.

“These results suggest that repetitive early-life brain injury may have later-life implications for cardiovascular health,” they wrote. They also noted that hypertension has been shown to independently increase the risk of cognitive decline.

While premature cognitive decline among ASF players is generally attributed to chronic traumatic encephalopathy, “data from the current study raise the possibility that some element of cognitive decline among former ASF players may be attributable to hypertension,” which is potentially treatable.

“Future studies clarifying associations and causal pathways between brain injury, hypertension, and brain health are warranted,” they concluded.

Dr. Baggish added, “We hope that clinicians will now understand that head injury is an independent risk factor for high blood pressure and will screen vulnerable populations accordingly, as this may lead to better recognition of previously underdiagnosed hypertension with subsequent opportunities for intervention.”
 

Close monitoring

Commenting on the study, Jonathan Kim, MD, chair-elect of the American College of Cardiology’s Sports–Cardiology Section and chief of sports cardiology at Emory University in Atlanta, said, “They clearly show an independent association, which is not causality but is a new finding that requires more research. To me, it really emphasizes that cardiovascular risk is the most important health consequence that we should be worried about in retired NFL [National Football League] players.

“There are multifactorial reasons – not just repetitive head trauma – why this athletic population is at risk for the development of high blood pressure, even among college players,” he said.

Dr. Kim’s team has shown in studies conducted in collaboration with Dr. Baggish and others that collegiate football players who gain weight and develop increased systolic blood pressure are at risk of developing a “pathologic” cardiovascular phenotype.

Other research from this group showed links between nonsteroidal anti-inflammatory drug use among high school and collegiate ASF players and increased cardiovascular risk, as well as ASF-associated hypertension and ventricular-arterial coupling. 

The suggestion that late-life hypertension could play a role in premature cognitive decline among ASF players “warrants further study,” Dr. Kim said, “because we do know that hypertension in the general population can be associated with cognitive decline. So that’s an important future direction.”

He concluded: “It’s a matter of focusing on cardiac prevention.” After their careers, players should be counseled on the importance of losing weight and adopting heart-healthy habits. In addition to some of the traditional concerns that might lead to closer follow-up of these patients, “having a lot of concussions in the history could potentially be another risk factor that should warrant close monitoring of blood pressure and, of course, treatment if necessary.”

The study was supported by Harvard Catalyst/the Harvard Clinical and Translational Science Center and the NFL Players Association. Dr. Baggish and several coauthors have received funding from the NFL Players Association.

A version of this article originally appeared on Medscape.com.

Among professional football players, the concussion burden during years of active play is associated with post-career high blood pressure, a new study suggests.

Among more than 4,000 participants, 37% had hypertension at a median of 24 years post career and reported a median concussion symptom score (CSS) of 23 on a scale of 0 to 130.

“We have long seen an incompletely explained link between football participation and later-life cardiovascular disease,” Aaron L. Baggish, MD, of Massachusetts Hospital and Harvard Medical School, Boston, told this news organization.

“This study tested [whether] concussion burden during years of active play would be a determinant of later-life hypertension, the most common cause of cardiovascular disease, and indeed found this relationship to be a strong one.”

The study was published online in Circulation.
 

Link to cognitive decline?

Dr. Baggish and colleagues recruited former professional American-style football (ASF) players to participate in a survey administered by the Football Players Health Study at Harvard University.

Concussion burden was quantified with respect to the occurrence and severity of common concussion symptoms – e.g., headaches, nausea, dizziness, confusion, loss of consciousness (LOC), disorientation, and feeling unsteady on one’s feet – over years of active participation.

Prevalent hypertension was determined either by the participants’ previously receiving from a clinician a recommendation for medication for “high blood pressure” or by the participants’ taking such medication at the time of survey completion. Diabetes status was determined by the participants’ receiving a prior recommendation for or prescription for “diabetes or high blood sugar” medication.

Of 15,070 invited to participate in the study, 4,168 did so. The mean age of the participants was 51.8 years; 39.4% were Black; the mean body mass index was 31.3; and 33.9% were linemen. Participants played for a mean of 6.9 seasons and were surveyed at a median 24.1 years post ASF career completion. The median CSS was 23.

A total of 1,542 participants (37.3%) had hypertension, and 8.8% had diabetes.

After adjustment for established hypertension risk factors, including smoking, race, diabetes, age, and BMI, there was a graded association between CSS category and odds of later-life hypertension and between high CSS exposure and prevalent hypertension.

Results persisted when LOC, a single highly specific severe concussion symptom, was used in isolation as a surrogate for CSS, the investigators noted.

“These results suggest that repetitive early-life brain injury may have later-life implications for cardiovascular health,” they wrote. They also noted that hypertension has been shown to independently increase the risk of cognitive decline.

While premature cognitive decline among ASF players is generally attributed to chronic traumatic encephalopathy, “data from the current study raise the possibility that some element of cognitive decline among former ASF players may be attributable to hypertension,” which is potentially treatable.

“Future studies clarifying associations and causal pathways between brain injury, hypertension, and brain health are warranted,” they concluded.

Dr. Baggish added, “We hope that clinicians will now understand that head injury is an independent risk factor for high blood pressure and will screen vulnerable populations accordingly, as this may lead to better recognition of previously underdiagnosed hypertension with subsequent opportunities for intervention.”
 

Close monitoring

Commenting on the study, Jonathan Kim, MD, chair-elect of the American College of Cardiology’s Sports–Cardiology Section and chief of sports cardiology at Emory University in Atlanta, said, “They clearly show an independent association, which is not causality but is a new finding that requires more research. To me, it really emphasizes that cardiovascular risk is the most important health consequence that we should be worried about in retired NFL [National Football League] players.

“There are multifactorial reasons – not just repetitive head trauma – why this athletic population is at risk for the development of high blood pressure, even among college players,” he said.

Dr. Kim’s team has shown in studies conducted in collaboration with Dr. Baggish and others that collegiate football players who gain weight and develop increased systolic blood pressure are at risk of developing a “pathologic” cardiovascular phenotype.

Other research from this group showed links between nonsteroidal anti-inflammatory drug use among high school and collegiate ASF players and increased cardiovascular risk, as well as ASF-associated hypertension and ventricular-arterial coupling. 

The suggestion that late-life hypertension could play a role in premature cognitive decline among ASF players “warrants further study,” Dr. Kim said, “because we do know that hypertension in the general population can be associated with cognitive decline. So that’s an important future direction.”

He concluded: “It’s a matter of focusing on cardiac prevention.” After their careers, players should be counseled on the importance of losing weight and adopting heart-healthy habits. In addition to some of the traditional concerns that might lead to closer follow-up of these patients, “having a lot of concussions in the history could potentially be another risk factor that should warrant close monitoring of blood pressure and, of course, treatment if necessary.”

The study was supported by Harvard Catalyst/the Harvard Clinical and Translational Science Center and the NFL Players Association. Dr. Baggish and several coauthors have received funding from the NFL Players Association.

A version of this article originally appeared on Medscape.com.

Among professional football players, the concussion burden during years of active play is associated with post-career high blood pressure, a new study suggests.

Among more than 4,000 participants, 37% had hypertension at a median of 24 years post career and reported a median concussion symptom score (CSS) of 23 on a scale of 0 to 130.

“We have long seen an incompletely explained link between football participation and later-life cardiovascular disease,” Aaron L. Baggish, MD, of Massachusetts Hospital and Harvard Medical School, Boston, told this news organization.

“This study tested [whether] concussion burden during years of active play would be a determinant of later-life hypertension, the most common cause of cardiovascular disease, and indeed found this relationship to be a strong one.”

The study was published online in Circulation.
 

Link to cognitive decline?

Dr. Baggish and colleagues recruited former professional American-style football (ASF) players to participate in a survey administered by the Football Players Health Study at Harvard University.

Concussion burden was quantified with respect to the occurrence and severity of common concussion symptoms – e.g., headaches, nausea, dizziness, confusion, loss of consciousness (LOC), disorientation, and feeling unsteady on one’s feet – over years of active participation.

Prevalent hypertension was determined either by the participants’ previously receiving from a clinician a recommendation for medication for “high blood pressure” or by the participants’ taking such medication at the time of survey completion. Diabetes status was determined by the participants’ receiving a prior recommendation for or prescription for “diabetes or high blood sugar” medication.

Of 15,070 invited to participate in the study, 4,168 did so. The mean age of the participants was 51.8 years; 39.4% were Black; the mean body mass index was 31.3; and 33.9% were linemen. Participants played for a mean of 6.9 seasons and were surveyed at a median 24.1 years post ASF career completion. The median CSS was 23.

A total of 1,542 participants (37.3%) had hypertension, and 8.8% had diabetes.

After adjustment for established hypertension risk factors, including smoking, race, diabetes, age, and BMI, there was a graded association between CSS category and odds of later-life hypertension and between high CSS exposure and prevalent hypertension.

Results persisted when LOC, a single highly specific severe concussion symptom, was used in isolation as a surrogate for CSS, the investigators noted.

“These results suggest that repetitive early-life brain injury may have later-life implications for cardiovascular health,” they wrote. They also noted that hypertension has been shown to independently increase the risk of cognitive decline.

While premature cognitive decline among ASF players is generally attributed to chronic traumatic encephalopathy, “data from the current study raise the possibility that some element of cognitive decline among former ASF players may be attributable to hypertension,” which is potentially treatable.

“Future studies clarifying associations and causal pathways between brain injury, hypertension, and brain health are warranted,” they concluded.

Dr. Baggish added, “We hope that clinicians will now understand that head injury is an independent risk factor for high blood pressure and will screen vulnerable populations accordingly, as this may lead to better recognition of previously underdiagnosed hypertension with subsequent opportunities for intervention.”
 

Close monitoring

Commenting on the study, Jonathan Kim, MD, chair-elect of the American College of Cardiology’s Sports–Cardiology Section and chief of sports cardiology at Emory University in Atlanta, said, “They clearly show an independent association, which is not causality but is a new finding that requires more research. To me, it really emphasizes that cardiovascular risk is the most important health consequence that we should be worried about in retired NFL [National Football League] players.

“There are multifactorial reasons – not just repetitive head trauma – why this athletic population is at risk for the development of high blood pressure, even among college players,” he said.

Dr. Kim’s team has shown in studies conducted in collaboration with Dr. Baggish and others that collegiate football players who gain weight and develop increased systolic blood pressure are at risk of developing a “pathologic” cardiovascular phenotype.

Other research from this group showed links between nonsteroidal anti-inflammatory drug use among high school and collegiate ASF players and increased cardiovascular risk, as well as ASF-associated hypertension and ventricular-arterial coupling. 

The suggestion that late-life hypertension could play a role in premature cognitive decline among ASF players “warrants further study,” Dr. Kim said, “because we do know that hypertension in the general population can be associated with cognitive decline. So that’s an important future direction.”

He concluded: “It’s a matter of focusing on cardiac prevention.” After their careers, players should be counseled on the importance of losing weight and adopting heart-healthy habits. In addition to some of the traditional concerns that might lead to closer follow-up of these patients, “having a lot of concussions in the history could potentially be another risk factor that should warrant close monitoring of blood pressure and, of course, treatment if necessary.”

The study was supported by Harvard Catalyst/the Harvard Clinical and Translational Science Center and the NFL Players Association. Dr. Baggish and several coauthors have received funding from the NFL Players Association.

A version of this article originally appeared on Medscape.com.

Stopping aspirin at 24-28 weeks of gestation has no disadvantage, compared with continuing aspirin full term, for preventing preterm preeclampsia in women at high risk of preeclampsia who have a normal fms-like tyrosine kinase 1 to placental growth factor (sFlt-1:PlGF) ratio, a randomized controlled trial has found.

The findings were published online in JAMA.
 

Editorialists advise careful consideration

However, in an accompanying editorial, Ukachi N. Emeruwa, MD, MPH, with the division of maternal fetal medicine, department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, and colleagues noted that the questions surrounding continuing or discontinuing aspirin in this high-risk population need further consideration.

They added that the results from this study – conducted in nine maternity hospitals across Spain – are hard to translate for the U.S. population.

In this study, Manel Mendoza, PhD, with the maternal fetal medicine unit, department of obstetrics, at the Universitat Autònoma de Barcelona, and colleagues compared the two approaches because of the potential to mitigate peripartum bleeding by discontinuing aspirin before full term (37 weeks’ gestation) and by an accurate selection of women in the first trimester at higher risk of preeclampsia.
 

Aspirin cuts preterm preeclampsia by 62% in women at high risk

While aspirin might be associated with an increased risk of peripartum bleeding, aspirin has been proven to reduce the incidence of preterm preeclampsia by 62% in pregnant women at high risk of preeclampsia.

In the multicenter, open-label, randomized, phase 3, noninferiority trial, pregnant women who had a high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24-28 weeks’ gestation were recruited between Aug. 20, 2019, and Sept. 15, 2021. Of those, 936 were analyzed (473 in the intervention group [stopping aspirin] and 473 in the control group [continuing]).

Screening for risk of preterm preeclampsia included analyzing maternal factors, uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein A, and placental growth factor. Follow-up was until delivery for all participants.

Incidence of preterm preeclampsia was 1.48% in the intervention group (discontinuing aspirin) and 1.73% in the control group (continuing aspirin until 36 weeks of gestation; absolute difference, –0.25%; 95% confidence interval, –1.86% to 1.36%), which indicates noninferiority for stopping aspirin. The bar for noninferiority was less than a 1.9% difference in preterm preeclampsia incidences between groups.

Researchers did find a higher incidence of minor antepartum bleeding in the group that continued aspirin (7.61% in the low-dose aspirin discontinuation group vs. 12.31% in the low-dose aspirin continuation group; absolute difference, –4.70; 95% CI, –8.53 to –0.87).
 

Differences in U.S. guidelines

Dr. Emeruwa and colleagues noted the study challenges a growing body of evidence favoring increasingly widespread use of low-dose aspirin in pregnancy.

They called the study “well designed and provocative,” but wrote that the findings are hard to interpret for a U.S. population. Some key differences in the U.S. preeclampsia prevention guidelines, compared with the practices of the study’s authors, included the reliance on clinical maternal factors in the United States for screening for low-dose aspirin prophylaxis as opposed to molecular biomarkers; a different aspirin dose prescribed in the United States (81 mg daily), compared with international societies (150 mg daily); and a lack of a recommendation in the United States to stop prophylactic low-dose aspirin at 36 weeks.

Dr. Emeruwa and colleagues also questioned the scope of the outcome measure used.

They wrote that limiting outcomes to preterm preeclampsia dims the effects of all types of preeclampsia on perinatal and maternal outcomes and that early-onset preeclampsia at less than 34 weeks “occurs in just 0.38% of pregnancies, while 3%-5% are affected by late-onset preeclampsia.”
 

‘Late-onset preeclampsia has a higher overall impact’

Dr. Emeruwa and colleagues wrote: “Though the odds of adverse perinatal and maternal outcomes are higher with preterm preeclampsia, due to its overall higher incidence, late-onset preeclampsia has a higher overall impact on perinatal and maternal morbidity and mortality.”

The study can inform future U.S. approaches, the editorialists wrote, and build on work already being done in the United States.

The study investigators used biophysical and molecular markers to more accurately assess risk for starting low-dose aspirin prophylaxis in the first trimester and applied a growing body of data showing the high negative predictive value of second-trimester biomarkers.

The editorialists noted that the U.S. Preventive Services Task Force recommendations would have captured “less than 50% of the at-risk population” that Dr. Mendoza’s team found eligible for low-dose aspirin.

Those factors, the editorialists wrote, point to the potential to improve guidelines for personalized preeclampsia management in pregnancy.

They concluded: “U.S. practitioners and professional societies should reconsider current risk assessment strategies, which are largely based on maternal factors, and evaluate whether incorporation of molecular biomarkers would improve maternal and fetal/neonatal outcomes.”

The study authors acknowledged that 92% of participants in the study were White, thus limiting generalizability.

The authors and editorialists reported no relevant financial relationships.

Stopping aspirin at 24-28 weeks of gestation has no disadvantage, compared with continuing aspirin full term, for preventing preterm preeclampsia in women at high risk of preeclampsia who have a normal fms-like tyrosine kinase 1 to placental growth factor (sFlt-1:PlGF) ratio, a randomized controlled trial has found.

The findings were published online in JAMA.
 

Editorialists advise careful consideration

However, in an accompanying editorial, Ukachi N. Emeruwa, MD, MPH, with the division of maternal fetal medicine, department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, and colleagues noted that the questions surrounding continuing or discontinuing aspirin in this high-risk population need further consideration.

They added that the results from this study – conducted in nine maternity hospitals across Spain – are hard to translate for the U.S. population.

In this study, Manel Mendoza, PhD, with the maternal fetal medicine unit, department of obstetrics, at the Universitat Autònoma de Barcelona, and colleagues compared the two approaches because of the potential to mitigate peripartum bleeding by discontinuing aspirin before full term (37 weeks’ gestation) and by an accurate selection of women in the first trimester at higher risk of preeclampsia.
 

Aspirin cuts preterm preeclampsia by 62% in women at high risk

While aspirin might be associated with an increased risk of peripartum bleeding, aspirin has been proven to reduce the incidence of preterm preeclampsia by 62% in pregnant women at high risk of preeclampsia.

In the multicenter, open-label, randomized, phase 3, noninferiority trial, pregnant women who had a high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24-28 weeks’ gestation were recruited between Aug. 20, 2019, and Sept. 15, 2021. Of those, 936 were analyzed (473 in the intervention group [stopping aspirin] and 473 in the control group [continuing]).

Screening for risk of preterm preeclampsia included analyzing maternal factors, uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein A, and placental growth factor. Follow-up was until delivery for all participants.

Incidence of preterm preeclampsia was 1.48% in the intervention group (discontinuing aspirin) and 1.73% in the control group (continuing aspirin until 36 weeks of gestation; absolute difference, –0.25%; 95% confidence interval, –1.86% to 1.36%), which indicates noninferiority for stopping aspirin. The bar for noninferiority was less than a 1.9% difference in preterm preeclampsia incidences between groups.

Researchers did find a higher incidence of minor antepartum bleeding in the group that continued aspirin (7.61% in the low-dose aspirin discontinuation group vs. 12.31% in the low-dose aspirin continuation group; absolute difference, –4.70; 95% CI, –8.53 to –0.87).
 

Differences in U.S. guidelines

Dr. Emeruwa and colleagues noted the study challenges a growing body of evidence favoring increasingly widespread use of low-dose aspirin in pregnancy.

They called the study “well designed and provocative,” but wrote that the findings are hard to interpret for a U.S. population. Some key differences in the U.S. preeclampsia prevention guidelines, compared with the practices of the study’s authors, included the reliance on clinical maternal factors in the United States for screening for low-dose aspirin prophylaxis as opposed to molecular biomarkers; a different aspirin dose prescribed in the United States (81 mg daily), compared with international societies (150 mg daily); and a lack of a recommendation in the United States to stop prophylactic low-dose aspirin at 36 weeks.

Dr. Emeruwa and colleagues also questioned the scope of the outcome measure used.

They wrote that limiting outcomes to preterm preeclampsia dims the effects of all types of preeclampsia on perinatal and maternal outcomes and that early-onset preeclampsia at less than 34 weeks “occurs in just 0.38% of pregnancies, while 3%-5% are affected by late-onset preeclampsia.”
 

‘Late-onset preeclampsia has a higher overall impact’

Dr. Emeruwa and colleagues wrote: “Though the odds of adverse perinatal and maternal outcomes are higher with preterm preeclampsia, due to its overall higher incidence, late-onset preeclampsia has a higher overall impact on perinatal and maternal morbidity and mortality.”

The study can inform future U.S. approaches, the editorialists wrote, and build on work already being done in the United States.

The study investigators used biophysical and molecular markers to more accurately assess risk for starting low-dose aspirin prophylaxis in the first trimester and applied a growing body of data showing the high negative predictive value of second-trimester biomarkers.

The editorialists noted that the U.S. Preventive Services Task Force recommendations would have captured “less than 50% of the at-risk population” that Dr. Mendoza’s team found eligible for low-dose aspirin.

Those factors, the editorialists wrote, point to the potential to improve guidelines for personalized preeclampsia management in pregnancy.

They concluded: “U.S. practitioners and professional societies should reconsider current risk assessment strategies, which are largely based on maternal factors, and evaluate whether incorporation of molecular biomarkers would improve maternal and fetal/neonatal outcomes.”

The study authors acknowledged that 92% of participants in the study were White, thus limiting generalizability.

The authors and editorialists reported no relevant financial relationships.

Stopping aspirin at 24-28 weeks of gestation has no disadvantage, compared with continuing aspirin full term, for preventing preterm preeclampsia in women at high risk of preeclampsia who have a normal fms-like tyrosine kinase 1 to placental growth factor (sFlt-1:PlGF) ratio, a randomized controlled trial has found.

The findings were published online in JAMA.
 

Editorialists advise careful consideration

However, in an accompanying editorial, Ukachi N. Emeruwa, MD, MPH, with the division of maternal fetal medicine, department of obstetrics, gynecology, and reproductive sciences at the University of California, San Diego, and colleagues noted that the questions surrounding continuing or discontinuing aspirin in this high-risk population need further consideration.

They added that the results from this study – conducted in nine maternity hospitals across Spain – are hard to translate for the U.S. population.

In this study, Manel Mendoza, PhD, with the maternal fetal medicine unit, department of obstetrics, at the Universitat Autònoma de Barcelona, and colleagues compared the two approaches because of the potential to mitigate peripartum bleeding by discontinuing aspirin before full term (37 weeks’ gestation) and by an accurate selection of women in the first trimester at higher risk of preeclampsia.
 

Aspirin cuts preterm preeclampsia by 62% in women at high risk

While aspirin might be associated with an increased risk of peripartum bleeding, aspirin has been proven to reduce the incidence of preterm preeclampsia by 62% in pregnant women at high risk of preeclampsia.

In the multicenter, open-label, randomized, phase 3, noninferiority trial, pregnant women who had a high risk of preeclampsia during the first-trimester screening and an sFlt-1:PlGF ratio of 38 or less at 24-28 weeks’ gestation were recruited between Aug. 20, 2019, and Sept. 15, 2021. Of those, 936 were analyzed (473 in the intervention group [stopping aspirin] and 473 in the control group [continuing]).

Screening for risk of preterm preeclampsia included analyzing maternal factors, uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein A, and placental growth factor. Follow-up was until delivery for all participants.

Incidence of preterm preeclampsia was 1.48% in the intervention group (discontinuing aspirin) and 1.73% in the control group (continuing aspirin until 36 weeks of gestation; absolute difference, –0.25%; 95% confidence interval, –1.86% to 1.36%), which indicates noninferiority for stopping aspirin. The bar for noninferiority was less than a 1.9% difference in preterm preeclampsia incidences between groups.

Researchers did find a higher incidence of minor antepartum bleeding in the group that continued aspirin (7.61% in the low-dose aspirin discontinuation group vs. 12.31% in the low-dose aspirin continuation group; absolute difference, –4.70; 95% CI, –8.53 to –0.87).
 

Differences in U.S. guidelines

Dr. Emeruwa and colleagues noted the study challenges a growing body of evidence favoring increasingly widespread use of low-dose aspirin in pregnancy.

They called the study “well designed and provocative,” but wrote that the findings are hard to interpret for a U.S. population. Some key differences in the U.S. preeclampsia prevention guidelines, compared with the practices of the study’s authors, included the reliance on clinical maternal factors in the United States for screening for low-dose aspirin prophylaxis as opposed to molecular biomarkers; a different aspirin dose prescribed in the United States (81 mg daily), compared with international societies (150 mg daily); and a lack of a recommendation in the United States to stop prophylactic low-dose aspirin at 36 weeks.

Dr. Emeruwa and colleagues also questioned the scope of the outcome measure used.

They wrote that limiting outcomes to preterm preeclampsia dims the effects of all types of preeclampsia on perinatal and maternal outcomes and that early-onset preeclampsia at less than 34 weeks “occurs in just 0.38% of pregnancies, while 3%-5% are affected by late-onset preeclampsia.”
 

‘Late-onset preeclampsia has a higher overall impact’

Dr. Emeruwa and colleagues wrote: “Though the odds of adverse perinatal and maternal outcomes are higher with preterm preeclampsia, due to its overall higher incidence, late-onset preeclampsia has a higher overall impact on perinatal and maternal morbidity and mortality.”

The study can inform future U.S. approaches, the editorialists wrote, and build on work already being done in the United States.

The study investigators used biophysical and molecular markers to more accurately assess risk for starting low-dose aspirin prophylaxis in the first trimester and applied a growing body of data showing the high negative predictive value of second-trimester biomarkers.

The editorialists noted that the U.S. Preventive Services Task Force recommendations would have captured “less than 50% of the at-risk population” that Dr. Mendoza’s team found eligible for low-dose aspirin.

Those factors, the editorialists wrote, point to the potential to improve guidelines for personalized preeclampsia management in pregnancy.

They concluded: “U.S. practitioners and professional societies should reconsider current risk assessment strategies, which are largely based on maternal factors, and evaluate whether incorporation of molecular biomarkers would improve maternal and fetal/neonatal outcomes.”

The study authors acknowledged that 92% of participants in the study were White, thus limiting generalizability.

The authors and editorialists reported no relevant financial relationships.

Drinking two or more cups of coffee a day was associated with twice the risk of death from cardiovascular disease among people with severe hypertension, according to researchers at Institute for Global Health Policy Research, Bureau of International Health Cooperation, National Center for Global Health and Medicine, Tokyo.

What to know

People with severely high blood pressure who drink two or more cups of caffeinated coffee each day could double their risk of dying from a heart attack, stroke, or any type of cardiovascular disease.

Too much coffee may raise blood pressure and lead to anxiety, heart palpitations, and difficulty sleeping.

An 8-ounce cup of coffee has 80-100 mg of caffeine, while an 8-ounce cup of green or black tea has 30-50 mg.

Drinking one cup of coffee a day or any amount of green tea was not associated with risk of death across any blood pressure categories, and drinking green tea was not associated with increased risk of death related to cardiovascular disease at any blood pressure level.

Frequent consumers of coffee were more likely to be younger, current smokers, current drinkers, to eat fewer vegetables, and to have higher total cholesterol levels and lower systolic blood pressure regardless of their blood pressure category.

This is a summary of the article “Coffee and Green Tea Consumption and Cardiovascular Disease Mortality Among People With and Without Hypertension,” published in the Journal of the American Heart Association.

A version of this article first appeared on Medscape.com.

Drinking two or more cups of coffee a day was associated with twice the risk of death from cardiovascular disease among people with severe hypertension, according to researchers at Institute for Global Health Policy Research, Bureau of International Health Cooperation, National Center for Global Health and Medicine, Tokyo.

What to know

People with severely high blood pressure who drink two or more cups of caffeinated coffee each day could double their risk of dying from a heart attack, stroke, or any type of cardiovascular disease.

Too much coffee may raise blood pressure and lead to anxiety, heart palpitations, and difficulty sleeping.

An 8-ounce cup of coffee has 80-100 mg of caffeine, while an 8-ounce cup of green or black tea has 30-50 mg.

Drinking one cup of coffee a day or any amount of green tea was not associated with risk of death across any blood pressure categories, and drinking green tea was not associated with increased risk of death related to cardiovascular disease at any blood pressure level.

Frequent consumers of coffee were more likely to be younger, current smokers, current drinkers, to eat fewer vegetables, and to have higher total cholesterol levels and lower systolic blood pressure regardless of their blood pressure category.

This is a summary of the article “Coffee and Green Tea Consumption and Cardiovascular Disease Mortality Among People With and Without Hypertension,” published in the Journal of the American Heart Association.

A version of this article first appeared on Medscape.com.

Drinking two or more cups of coffee a day was associated with twice the risk of death from cardiovascular disease among people with severe hypertension, according to researchers at Institute for Global Health Policy Research, Bureau of International Health Cooperation, National Center for Global Health and Medicine, Tokyo.

What to know

People with severely high blood pressure who drink two or more cups of caffeinated coffee each day could double their risk of dying from a heart attack, stroke, or any type of cardiovascular disease.

Too much coffee may raise blood pressure and lead to anxiety, heart palpitations, and difficulty sleeping.

An 8-ounce cup of coffee has 80-100 mg of caffeine, while an 8-ounce cup of green or black tea has 30-50 mg.

Drinking one cup of coffee a day or any amount of green tea was not associated with risk of death across any blood pressure categories, and drinking green tea was not associated with increased risk of death related to cardiovascular disease at any blood pressure level.

Frequent consumers of coffee were more likely to be younger, current smokers, current drinkers, to eat fewer vegetables, and to have higher total cholesterol levels and lower systolic blood pressure regardless of their blood pressure category.

This is a summary of the article “Coffee and Green Tea Consumption and Cardiovascular Disease Mortality Among People With and Without Hypertension,” published in the Journal of the American Heart Association.

A version of this article first appeared on Medscape.com.

Bradycardia is a lot more common than generally believed, but is often asymptomatic and not clinically relevant, and may lead to needless pacemaker therapy, suggests a post hoc analysis of a major study.

The arrhythmia’s presence overall in the randomized LOOP trial predicted an excess risk of syncope and death, and it didn’t matter how it was detected. Bradyarrhythmia revealed incidentally at long-term cardiac rhythm monitoring was no more predictive than when it was picked up in a usual-care setting.

Still, people in the trial with implantable loop recorders (ILR) had six times the chance of being diagnosed with bradyarrhythmias than those in the usual-care control group. LOOP entered older persons in the community without known arrhythmias but with risk factors like diabetes or hypertension.

About 80% of such arrhythmias at ILR monitoring were asymptomatic, compared with less than one-fourth in the usual-care group. Yet pacemaker implantation for bradyarrhythmia was 53% more likely in the ILR group, according to a report published in JAMA Cardiology.

Most participants with asymptomatic bradycardia did not receive treatment for it, yet the study – despite the mostly conservative management – still showed “overtreatment with pacemakers” in the ILR group, observed lead author Søren Zöga Diederichsen, MD, PhD, Copenhagen University Hospital–Rigshospitalet.

Bradyarrhythmia overall predicted later syncope and all-cause and cardiovascular (CV) death, but did so regardless of whether the patient was ILR monitored or received a pacemaker, Diederichsen said in an interview.

“We didn’t see any signal, not even a small signal, toward a health benefit from monitoring and detecting bradycardias, or from acting on them conservatively or implanting pacemakers,” he noted.

The study “emphasizes that you should have symptoms” to justify pacemaker therapy for bradyarrhythmias, regardless of how they were detected, Dr. Diederichsen said.

“Clearly ILRs may identify patients with bradyarrhythmias deserving of treatment” when they are associated with symptoms, an accompanying editorial agreed. In the current analysis, however, “a large proportion of bradycardic events were completely asymptomatic.” Yet bradycardia predicted syncope and CV death in both the ILR and usual care groups, it noted.

“This does raise the question as to whether bradyarrhythmia may be a risk marker for underlying nonarrhythmic conditions to which preventive strategies and treatment should be directed,” wrote editorialists Mark H. Schoenfeld, MD, Yale University, New Haven, Conn., and Kristen K. Patton, MD, University of Washington, Seattle.

“In an aging population with ever-increasing comorbidities, it may become increasingly important to rule out bradycardia as a manifestation of a more sinister underlying disease,” they noted, and to identify “patients who may be particularly vulnerable to adverse outcomes of progressive distal conduction disease.”

The previously published LOOP trial, conducted at four sites in Denmark, compared ILR screening for atrial fibrillation to usual care in 6,004 patients at least 70 years or older, most with hypertension. The main results showed little benefit from screening for atrial fibrillation in prevention of incident stroke or systemic embolism over about 5 years.

The current LOOP analysis, post hoc with all the associated limitations, followed incident bradyarrhythmia in the ILR and usual-care groups; any treatment of the arrhythmia was at physician discretion. The total cohort averaged 75 years in age and 47.3% were women.

The rate of incident bradyarrhythmia was 8.1% overall; it was 20.8% for those with ILR monitoring and 3.8% in the usual care group, for a hazard ratio of 6.21 (95% confidence interval, 5.15-7.48, P < .001).

The arrhythmia was asymptomatic in 23.8% of usual-care patients and 79.8% of those with an ILR.

Bradyarrhythmia was significantly more likely among older patients, male patients, and those with a history of syncope, the group reported.

Pacemakers were implanted for bradyarrhythmia in 2.9% of usual-care patients and 4.5% of those with ILR monitoring for an HR of 1.53 (95% CI, 1.14-2.06, P < .001).

Among usual-care patients, bradyarrhythmia (vs no bradyarrhythmia) was associated with 5.2 times the risk for incident syncope (P < .001). That risk for syncope went up 2.6 times (P = .01) in the ILR group.

The corresponding risks for CV death among controls and among ILR patients increased 4.8 times (P < .001) and by 3.1 (P < .001), respectively. The risks for death from any cause tripled (P < .001) and rose 2.5 times (P < .001) among bradycardic controls and ILR patients, respectively.

Bradyarrhythmia was not significantly related to sudden cardiac death in either group, the report noted.

Given the increasing use of heart rhythm monitoring “inside and outside the clinical setting,” it stated, “bradyarrhythmias are likely to be detected more often, sometimes as an incidental finding. Knowledge about the underlying prevalence and prognostic significance could help guide decisions.”

The study “teaches us a little bit” about the true prevalence of bradyarrhythmias in the general population, including asymptomatic cases that appear to be subclinical or “physiological,” Dr. Diederichsen said in an interview.

It also suggests that such bradycardia will be increasingly observed as use of ILR for arrhythmia screening expands in practice, he predicted. It may also be picked up more often by wearables and other rhythm-monitoring technology used by the public.

In the latter case especially, Dr. Diederichsen said, the current analysis could potentially help alleviate any concerns that bradyarrhythmia without symptoms is something that has to be specifically treated.

Dr. Diederichsen disclosed grants from several Danish research institutions, R. og Hustrus Fond, and Medtronic, as well as receiving personal fees from Vital Beats and Bristol-Myers Squibb/Pfizer. Dr. Schoenfeld reported ownership of stock from Apple. Dr. Patton reported employment as a medical officer for the Food and Drug Administration and serving as associate editor for JAMA Cardiology.

A version of this article originally appeared on Medscape.com.

Bradycardia is a lot more common than generally believed, but is often asymptomatic and not clinically relevant, and may lead to needless pacemaker therapy, suggests a post hoc analysis of a major study.

The arrhythmia’s presence overall in the randomized LOOP trial predicted an excess risk of syncope and death, and it didn’t matter how it was detected. Bradyarrhythmia revealed incidentally at long-term cardiac rhythm monitoring was no more predictive than when it was picked up in a usual-care setting.

Still, people in the trial with implantable loop recorders (ILR) had six times the chance of being diagnosed with bradyarrhythmias than those in the usual-care control group. LOOP entered older persons in the community without known arrhythmias but with risk factors like diabetes or hypertension.

About 80% of such arrhythmias at ILR monitoring were asymptomatic, compared with less than one-fourth in the usual-care group. Yet pacemaker implantation for bradyarrhythmia was 53% more likely in the ILR group, according to a report published in JAMA Cardiology.

Most participants with asymptomatic bradycardia did not receive treatment for it, yet the study – despite the mostly conservative management – still showed “overtreatment with pacemakers” in the ILR group, observed lead author Søren Zöga Diederichsen, MD, PhD, Copenhagen University Hospital–Rigshospitalet.

Bradyarrhythmia overall predicted later syncope and all-cause and cardiovascular (CV) death, but did so regardless of whether the patient was ILR monitored or received a pacemaker, Diederichsen said in an interview.

“We didn’t see any signal, not even a small signal, toward a health benefit from monitoring and detecting bradycardias, or from acting on them conservatively or implanting pacemakers,” he noted.

The study “emphasizes that you should have symptoms” to justify pacemaker therapy for bradyarrhythmias, regardless of how they were detected, Dr. Diederichsen said.

“Clearly ILRs may identify patients with bradyarrhythmias deserving of treatment” when they are associated with symptoms, an accompanying editorial agreed. In the current analysis, however, “a large proportion of bradycardic events were completely asymptomatic.” Yet bradycardia predicted syncope and CV death in both the ILR and usual care groups, it noted.

“This does raise the question as to whether bradyarrhythmia may be a risk marker for underlying nonarrhythmic conditions to which preventive strategies and treatment should be directed,” wrote editorialists Mark H. Schoenfeld, MD, Yale University, New Haven, Conn., and Kristen K. Patton, MD, University of Washington, Seattle.

“In an aging population with ever-increasing comorbidities, it may become increasingly important to rule out bradycardia as a manifestation of a more sinister underlying disease,” they noted, and to identify “patients who may be particularly vulnerable to adverse outcomes of progressive distal conduction disease.”

The previously published LOOP trial, conducted at four sites in Denmark, compared ILR screening for atrial fibrillation to usual care in 6,004 patients at least 70 years or older, most with hypertension. The main results showed little benefit from screening for atrial fibrillation in prevention of incident stroke or systemic embolism over about 5 years.

The current LOOP analysis, post hoc with all the associated limitations, followed incident bradyarrhythmia in the ILR and usual-care groups; any treatment of the arrhythmia was at physician discretion. The total cohort averaged 75 years in age and 47.3% were women.

The rate of incident bradyarrhythmia was 8.1% overall; it was 20.8% for those with ILR monitoring and 3.8% in the usual care group, for a hazard ratio of 6.21 (95% confidence interval, 5.15-7.48, P < .001).

The arrhythmia was asymptomatic in 23.8% of usual-care patients and 79.8% of those with an ILR.

Bradyarrhythmia was significantly more likely among older patients, male patients, and those with a history of syncope, the group reported.

Pacemakers were implanted for bradyarrhythmia in 2.9% of usual-care patients and 4.5% of those with ILR monitoring for an HR of 1.53 (95% CI, 1.14-2.06, P < .001).

Among usual-care patients, bradyarrhythmia (vs no bradyarrhythmia) was associated with 5.2 times the risk for incident syncope (P < .001). That risk for syncope went up 2.6 times (P = .01) in the ILR group.

The corresponding risks for CV death among controls and among ILR patients increased 4.8 times (P < .001) and by 3.1 (P < .001), respectively. The risks for death from any cause tripled (P < .001) and rose 2.5 times (P < .001) among bradycardic controls and ILR patients, respectively.

Bradyarrhythmia was not significantly related to sudden cardiac death in either group, the report noted.

Given the increasing use of heart rhythm monitoring “inside and outside the clinical setting,” it stated, “bradyarrhythmias are likely to be detected more often, sometimes as an incidental finding. Knowledge about the underlying prevalence and prognostic significance could help guide decisions.”

The study “teaches us a little bit” about the true prevalence of bradyarrhythmias in the general population, including asymptomatic cases that appear to be subclinical or “physiological,” Dr. Diederichsen said in an interview.

It also suggests that such bradycardia will be increasingly observed as use of ILR for arrhythmia screening expands in practice, he predicted. It may also be picked up more often by wearables and other rhythm-monitoring technology used by the public.

In the latter case especially, Dr. Diederichsen said, the current analysis could potentially help alleviate any concerns that bradyarrhythmia without symptoms is something that has to be specifically treated.

Dr. Diederichsen disclosed grants from several Danish research institutions, R. og Hustrus Fond, and Medtronic, as well as receiving personal fees from Vital Beats and Bristol-Myers Squibb/Pfizer. Dr. Schoenfeld reported ownership of stock from Apple. Dr. Patton reported employment as a medical officer for the Food and Drug Administration and serving as associate editor for JAMA Cardiology.

A version of this article originally appeared on Medscape.com.

Bradycardia is a lot more common than generally believed, but is often asymptomatic and not clinically relevant, and may lead to needless pacemaker therapy, suggests a post hoc analysis of a major study.

The arrhythmia’s presence overall in the randomized LOOP trial predicted an excess risk of syncope and death, and it didn’t matter how it was detected. Bradyarrhythmia revealed incidentally at long-term cardiac rhythm monitoring was no more predictive than when it was picked up in a usual-care setting.

Still, people in the trial with implantable loop recorders (ILR) had six times the chance of being diagnosed with bradyarrhythmias than those in the usual-care control group. LOOP entered older persons in the community without known arrhythmias but with risk factors like diabetes or hypertension.

About 80% of such arrhythmias at ILR monitoring were asymptomatic, compared with less than one-fourth in the usual-care group. Yet pacemaker implantation for bradyarrhythmia was 53% more likely in the ILR group, according to a report published in JAMA Cardiology.

Most participants with asymptomatic bradycardia did not receive treatment for it, yet the study – despite the mostly conservative management – still showed “overtreatment with pacemakers” in the ILR group, observed lead author Søren Zöga Diederichsen, MD, PhD, Copenhagen University Hospital–Rigshospitalet.

Bradyarrhythmia overall predicted later syncope and all-cause and cardiovascular (CV) death, but did so regardless of whether the patient was ILR monitored or received a pacemaker, Diederichsen said in an interview.

“We didn’t see any signal, not even a small signal, toward a health benefit from monitoring and detecting bradycardias, or from acting on them conservatively or implanting pacemakers,” he noted.

The study “emphasizes that you should have symptoms” to justify pacemaker therapy for bradyarrhythmias, regardless of how they were detected, Dr. Diederichsen said.

“Clearly ILRs may identify patients with bradyarrhythmias deserving of treatment” when they are associated with symptoms, an accompanying editorial agreed. In the current analysis, however, “a large proportion of bradycardic events were completely asymptomatic.” Yet bradycardia predicted syncope and CV death in both the ILR and usual care groups, it noted.

“This does raise the question as to whether bradyarrhythmia may be a risk marker for underlying nonarrhythmic conditions to which preventive strategies and treatment should be directed,” wrote editorialists Mark H. Schoenfeld, MD, Yale University, New Haven, Conn., and Kristen K. Patton, MD, University of Washington, Seattle.

“In an aging population with ever-increasing comorbidities, it may become increasingly important to rule out bradycardia as a manifestation of a more sinister underlying disease,” they noted, and to identify “patients who may be particularly vulnerable to adverse outcomes of progressive distal conduction disease.”

The previously published LOOP trial, conducted at four sites in Denmark, compared ILR screening for atrial fibrillation to usual care in 6,004 patients at least 70 years or older, most with hypertension. The main results showed little benefit from screening for atrial fibrillation in prevention of incident stroke or systemic embolism over about 5 years.

The current LOOP analysis, post hoc with all the associated limitations, followed incident bradyarrhythmia in the ILR and usual-care groups; any treatment of the arrhythmia was at physician discretion. The total cohort averaged 75 years in age and 47.3% were women.

The rate of incident bradyarrhythmia was 8.1% overall; it was 20.8% for those with ILR monitoring and 3.8% in the usual care group, for a hazard ratio of 6.21 (95% confidence interval, 5.15-7.48, P < .001).

The arrhythmia was asymptomatic in 23.8% of usual-care patients and 79.8% of those with an ILR.

Bradyarrhythmia was significantly more likely among older patients, male patients, and those with a history of syncope, the group reported.

Pacemakers were implanted for bradyarrhythmia in 2.9% of usual-care patients and 4.5% of those with ILR monitoring for an HR of 1.53 (95% CI, 1.14-2.06, P < .001).

Among usual-care patients, bradyarrhythmia (vs no bradyarrhythmia) was associated with 5.2 times the risk for incident syncope (P < .001). That risk for syncope went up 2.6 times (P = .01) in the ILR group.

The corresponding risks for CV death among controls and among ILR patients increased 4.8 times (P < .001) and by 3.1 (P < .001), respectively. The risks for death from any cause tripled (P < .001) and rose 2.5 times (P < .001) among bradycardic controls and ILR patients, respectively.

Bradyarrhythmia was not significantly related to sudden cardiac death in either group, the report noted.

Given the increasing use of heart rhythm monitoring “inside and outside the clinical setting,” it stated, “bradyarrhythmias are likely to be detected more often, sometimes as an incidental finding. Knowledge about the underlying prevalence and prognostic significance could help guide decisions.”

The study “teaches us a little bit” about the true prevalence of bradyarrhythmias in the general population, including asymptomatic cases that appear to be subclinical or “physiological,” Dr. Diederichsen said in an interview.

It also suggests that such bradycardia will be increasingly observed as use of ILR for arrhythmia screening expands in practice, he predicted. It may also be picked up more often by wearables and other rhythm-monitoring technology used by the public.

In the latter case especially, Dr. Diederichsen said, the current analysis could potentially help alleviate any concerns that bradyarrhythmia without symptoms is something that has to be specifically treated.

Dr. Diederichsen disclosed grants from several Danish research institutions, R. og Hustrus Fond, and Medtronic, as well as receiving personal fees from Vital Beats and Bristol-Myers Squibb/Pfizer. Dr. Schoenfeld reported ownership of stock from Apple. Dr. Patton reported employment as a medical officer for the Food and Drug Administration and serving as associate editor for JAMA Cardiology.

A version of this article originally appeared on Medscape.com.

On June 14, 2017, just before noon, a doctor made an incision near a patient’s groin. Kari Kirk, a representative for the world’s largest medical device company, Medtronic, looked on and began texting her colleague a play-by-play.

“Fixing both legs from the ankles,” she wrote.

It was a fairly common procedure at the Robert J. Dole Veterans Affairs Medical Center in Wichita, Kansas, performed to treat blockages in the leg vessels.

Within reach were an array of Medtronic products: tubes with blades attached to shave hardened deposits off of artery walls; stents to widen blood vessels; balloons coated with therapeutic drugs.

Each time a doctor puts a foreign device in someone’s body, it carries a risk of complication, which can include clots or even require amputation. So medical experts, research and even Medtronic’s own device instructions urge doctors to use as few as are necessary.

But, as revealed in Kirk’s text messages, this doctor took an aggressive approach.

“Just used 12 [drug-coated balloons]!!” Kirk texted her colleague.

“Does that mean I owe u $$,” he responded.

“Thats what I’m thinking!!!” she said. “And now 14 balloons?!”

“but only one stent so far??”

“So far!”

As the texting continued, her colleague replied, “U are going to want to start going to the VA all the time.”

The messages, recently unsealed in an ongoing whistleblower lawsuit, give a window into the way money and medicine mingle in the booming business of peripheral artery disease, a condition that afflicts 6.5 million Americans over age 40 and is caused when fatty plaque builds up in arteries, blocking blood flow to the legs.

Representatives from companies are often present during vascular procedures to guide doctors on how to use their complex devices. This kind of access has the potential to influence treatment plans, as companies and their representatives profit when more of their product is used.

The suit, filed in 2017 by a sales representative for a competing medical device firm, alleges an illegal kickback scheme between Medtronic and hospital employees. According to the complaint and documents released in the suit, between 2011 and 2018, VA health care workers received steakhouse dinners, Apple electronics, and NASCAR tickets, and in turn, Medtronic secured a lucrative contract with the hospital. Meanwhile, the company’s representatives allegedly “groomed and trained” physicians at the facility, who then deployed the company’s devices even when it was not medically indicated.

Independently from the whistleblower suit, internal investigators at the Wichita facility have also examined the treatment patterns of its vascular patients in recent years and found numerous cases where medical devices were used excessively. While it’s not uncommon to deploy several devices, a medical expert on the investigation team found that the VA doctors sometimes used more than 15 at a time – one used 33 – deviating from the standard of care.

“It is unconscionable – there can be no valid medically acceptable basis to cram so many devices into a human being,” wrote attorneys representing the whistleblower in legal filings from January 2023. “This is not medical treatment. This is abuse.”

Dr. Kim Hodgson, former president of the Society for Vascular Surgery and an expert retained by the plaintiff, said the findings of the internal review of patient data raise “a high level of concern regarding necessity of treatment provided,” according to case documents.

Medtronic declined to respond to ProPublica’s questions, citing the ongoing litigation. “These allegations are false and Medtronic is defending against these claims in court,” said Boua Xiong, a spokesperson for the company. Medtronic representative Kirk declined to respond to ProPublica’s request for comment.

The hospital investigation found that amputations increased sixfold in the same time frame as the procedures in question, according to internal emails, but made no conclusion about whether those two things were connected. ProPublica reached out to the VA to ask whether any patients had been harmed.

The VA is “conducting an extensive review of patient care” at the Kansas hospital, “including the number of devices used on patients – to make sure that Veterans were not harmed by any procedures,” press secretary Terrence Hayes said in a statement. So far, the VA’s investigation has found no “quality of care issues,” he said, and the investigation will continue “until every Veteran’s case has been reviewed.” (Read the full statement here.) Neither the department nor the hospital has taken formal action against the medical providers, Hayes said.

The medical group that had a contract with the VA for vascular interventions, Wichita Radiological Group, did not respond to ProPublica’s requests for comment, nor did the doctors named in the suit: Dr. Shaun Gonda, Dr. Bret Winblad, and Dr. Kermit Rust. It is unclear from the case documents which doctors conducted which procedures. Eric Barth, an attorney for the medical group, denied the allegations in recent legal filings, calling the claims “baseless” and the lawsuit a “witch hunt.”

The lawsuit comes amid growing concern about one of these procedures – atherectomies – after researchers and doctors have uncovered patterns of excessive and inappropriate use. Recent research has found that this procedure, a common but costly treatment to shave or laser plaque from blood vessels, is not more effective than cheaper alternatives and may even be associated with a higher risk of complications including amputation. In recent years, several doctors and clinics have been investigated for allegedly taking advantage of Medicare’s reimbursement rates, and one study found that many doctors are resorting to atherectomies in the earliest stages of peripheral artery disease, against best practices that urge noninvasive treatment.

“Atherectomy is important in certain settings. But it’s being used in a way that is entirely inappropriate and it’s largely driven by the incentive structure,” said Dr. Caitlin Hicks, the lead author of the study and an associate professor of surgery at Johns Hopkins University School of Medicine.

Although different payment structures govern the care of veterans, the whistleblower lawsuit alleges that outside physicians, paid hourly by the Dole VA, were motivated to conduct longer and more complex procedures that would earn them higher payment.

Under different circumstances, the patient in the procedure room on that summer day could have been done after 2 hours.

But, 150 minutes in, those Medtronic representatives were still texting. At that point, more than 15 of their vascular devices had been used, including stents, balloons, and those for atherectomy.

“Long case!” Kirk’s colleague texted. “Is it looking ok??”

“It is,” she said. “Thought we were done a few times! Now he’s going back in to cut again!”

A little while later, she texted: “....17!”

He texted back [with laughing emoticons].

Hospital leaders had been scrutinizing the use of these procedures at the Dole VA for years.

In 2017, shortly after Rick Ament was hired to lead the facility, he noticed something was amiss. While the longtime hospital administrator was poring over the finances, he was alarmed to discover that the relatively small Dole VA had one of the most expensive cardiac programs in the country. As Ament dug deeper, he realized vascular interventions were the reason.

“It just did not make sense that the acuity level of our patients would generate such extreme cost variances from the norm,” he testified in December, in a deposition for the whistleblower case. “It was so significant, we needed to get to the bottom of it.”

Ament, a second generation Air Force veteran, quietly assembled a task force to investigate why the facility had purchased so many medical devices for these procedures. After they examined inventory records, calculating the total number of medical devices and the cost of devices per patient, they grew concerned.

“We were more expensive than, I believe it was, the top 10 hospitals in the VA combined,” he said. “My feeling was that we either had very, very bad providers or we had product walking out the door.”

Ament enlisted experts from other VA hospitals to help his team investigate, including an administrative officer who could understand finances and a respected interventional radiologist who could examine records. The task force gathered a list of patients from 2016 to 2018, according to internal emails, and analyzed their medical charts.

According to internal VA documents released through the whistleblower suit, the review found a number of clinical failings: Evidence-based medicine had not been followed in the majority of cases reviewed. Procedures were over-aggressive, treating lesions that should have been left alone. And there was a total disregard for established best practices for treating peripheral artery disease.

One of the experts on the investigative team explained to Ament that while it was not uncommon for doctors to use a couple of devices in one intervention, the total number of devices in many of the procedures at his facility went into the double digits, sometimes five times the expected amount.

In one encounter, a doctor deployed 33 devices in one procedure – 3 atherectomy devices, 9 stents, and 21 balloons.

This use of devices was exorbitant, Ament came to understand. “I want to say the term ‘egregious’ was used,” he testified. “It was kind of like validation, but I really wish I was wrong.”

“Did it make you concerned for patient care?” a lawyer asked during the deposition.

“It did,” Ament replied.

A member of his task force pulled data for veterans who had leg amputations due to vascular disease. Over 5 years, the number of veterans who had amputations increased, from about 6 in 2013 to 38 in 2018, according to internal emails released in the suit. The VA did not respond to ProPublica’s questions about the rise in amputations or whether it was due to complications from the procedures.

Even though Ament testified in December 2022 that he became aware of the excessive use of devices during his investigation that began about 5 years ago, neither he nor the VA have publicly acknowledged these findings outside of the lawsuit. It is unclear whether VA representatives informed the patients whose records were reviewed about their findings. ProPublica reached out to more than half a dozen veteran community groups in the Wichita area and none were aware of the investigation nor the allegations of overuse of vascular procedures at the facility.

The VA says that if its ongoing review finds instances of substandard care, it will reach out to affected patients and inform them about possible complications and benefits they may be entitled to. The press secretary said the review will take several months. Ament declined to respond to ProPublica’s questions, citing the ongoing case.

In 2018, Ament turned over his findings to the criminal division of the VA’s Office of Inspector General. He also shut down interventional radiology procedures at the facility’s catheter lab.

Federal agents separately opened an investigation into the same unit in the facility, looking into allegations of kickbacks.

More than 40 pages of expense reports from Medtronic, revealed in the whistleblower case, show sales representatives treating Dole health care workers to hundreds of meals over several years – lunches at Dempsey’s Biscuit Co.; business meals at the Scotch & Sirloin steakhouse; dinner at Chester’s Chophouse & Wine Bar, price per attendee: $122.39.

Federal agents obtained the receipts.

“Robert J. Dole VAMC employees may have received improper gratuities, in the forms of paid lunches, dinners, etc., from sales representatives from Medtronic,” Nathen Howard, a special agent in the VA OIG, wrote in an investigation memo from February 2019.

This kind of relationship could violate VA policy, which forbids federal employees from receiving any gifts, including meals, from people who do business or seek to do business with a federal institution. For health care workers, violating this policy could have serious implications for patients. Numerous studies have shown that even modest industry-sponsored gifts, including meals, may influence prescribing or treatment behavior of health care professionals.

The agents opened their investigation into kickbacks at the Wichita facility in response to the whistleblower lawsuit, which was filed by Thomas Schroeder in 2017. The VA OIG would not confirm or deny whether it was continuing to investigate kickbacks at the facility. The VA did not directly answer ProPublica’s questions about kickbacks at the Dole VA, but it said that every employee must complete an annual ethics training, which covers gift rules.

In recent years, Medtronic has settled a handful of other cases that have alleged kickbacks between company representatives and health care professionals.

In 2018, Medtronic’s subsidiary Covidien paid $13 million to settle claims with the U.S. Department of Justice that it paid kickbacks to health care institutions that used its mechanical blood clot devices. In 2019, the same subsidiary paid $17 million to resolve allegations that it provided in-kind marketing support to doctors using its vein products. And in 2020, Medtronic paid more than $8 million to settle claims that representatives had paid kickbacks to a neurosurgeon, including scores of lavish meals at a restaurant that the doctor owned, to induce him to purchase the company’s medication pumps.

Schroeder’s lawsuit is not the first time Medtronic’s vascular devices were named in an alleged kickback scheme. In early 2015, Medtronic acquired Covidien, and shortly after the merger, its subsidiary ev3 Inc. agreed to pay $1.25 million to resolve allegations that it had paid doctors who were “high volume users” of its atherectomy devices to act as evangelists for the company, and had provided physicians with company shares to participate in clinical trials for their tools.

The whistleblower in this earlier case, a former sales representative for the company, also alleged that the subsidiary was gaming Medicare’s payment system. Hospitals were often hesitant to conduct atherectomy procedures because of the low reimbursement rates. According to the suit, sales representatives encouraged doctors to admit patients for longer stays to reap greater reimbursements and make a profit, even though such stays were often not medically indicated.

“Medical device makers that try to boost their profits by causing patients to be admitted for unnecessary and expensive inpatient hospital stays will be held accountable,” special agent Thomas O’Donnell, from the Office of Inspector General at the U.S. Department of Health and Human Services, said in a press release for the settlement. “Both patients and taxpayers deserve to have medical decisions made based on what is medically appropriate.”

Medtronic spokesperson Xiong said that in each case, the company “cooperated fully with the DOJ to resolve its concerns and, where wrongdoing was found, took appropriate remedial action.”

Seton Hall Law School professor Jacob Elberg, a former assistant U.S. attorney for the District of New Jersey who led its health care and government fraud unit, is concerned by the frequency of such settlements in the last 2 decades. “There are, at this point, real questions as to whether the sanctions imposed by DOJ are sufficient to deter wrongdoing and to lead to meaningful change, especially within the medical device industry.”

Although the Department of Justice has declined to intervene in the lawsuit involving the Dole VA at this time, the case is ongoing and further depositions with Medtronic sales representatives and a former VA employee are scheduled for this month.

VA employees and doctors named in the suit declined to comment or did not respond to ProPublica’s questions about the alleged kickbacks and whether sales representatives may have influenced veterans’ treatment plans. In interviews with federal investigators, according to released transcripts, several of the employees who were questioned denied receiving frequent meals from sales representatives, contradicting Medtronic’s expense reports.

Their statements also stand in contrast to Medtronic representative Kari Kirk’s final text messages during that procedure in June 2017, which ultimately lasted more than 3 hours.

“Now u done??” her colleague asked.

“Just finished,” she texted. “Running to get them lunch!”

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

On June 14, 2017, just before noon, a doctor made an incision near a patient’s groin. Kari Kirk, a representative for the world’s largest medical device company, Medtronic, looked on and began texting her colleague a play-by-play.

“Fixing both legs from the ankles,” she wrote.

It was a fairly common procedure at the Robert J. Dole Veterans Affairs Medical Center in Wichita, Kansas, performed to treat blockages in the leg vessels.

Within reach were an array of Medtronic products: tubes with blades attached to shave hardened deposits off of artery walls; stents to widen blood vessels; balloons coated with therapeutic drugs.

Each time a doctor puts a foreign device in someone’s body, it carries a risk of complication, which can include clots or even require amputation. So medical experts, research and even Medtronic’s own device instructions urge doctors to use as few as are necessary.

But, as revealed in Kirk’s text messages, this doctor took an aggressive approach.

“Just used 12 [drug-coated balloons]!!” Kirk texted her colleague.

“Does that mean I owe u $$,” he responded.

“Thats what I’m thinking!!!” she said. “And now 14 balloons?!”

“but only one stent so far??”

“So far!”

As the texting continued, her colleague replied, “U are going to want to start going to the VA all the time.”

The messages, recently unsealed in an ongoing whistleblower lawsuit, give a window into the way money and medicine mingle in the booming business of peripheral artery disease, a condition that afflicts 6.5 million Americans over age 40 and is caused when fatty plaque builds up in arteries, blocking blood flow to the legs.

Representatives from companies are often present during vascular procedures to guide doctors on how to use their complex devices. This kind of access has the potential to influence treatment plans, as companies and their representatives profit when more of their product is used.

The suit, filed in 2017 by a sales representative for a competing medical device firm, alleges an illegal kickback scheme between Medtronic and hospital employees. According to the complaint and documents released in the suit, between 2011 and 2018, VA health care workers received steakhouse dinners, Apple electronics, and NASCAR tickets, and in turn, Medtronic secured a lucrative contract with the hospital. Meanwhile, the company’s representatives allegedly “groomed and trained” physicians at the facility, who then deployed the company’s devices even when it was not medically indicated.

Independently from the whistleblower suit, internal investigators at the Wichita facility have also examined the treatment patterns of its vascular patients in recent years and found numerous cases where medical devices were used excessively. While it’s not uncommon to deploy several devices, a medical expert on the investigation team found that the VA doctors sometimes used more than 15 at a time – one used 33 – deviating from the standard of care.

“It is unconscionable – there can be no valid medically acceptable basis to cram so many devices into a human being,” wrote attorneys representing the whistleblower in legal filings from January 2023. “This is not medical treatment. This is abuse.”

Dr. Kim Hodgson, former president of the Society for Vascular Surgery and an expert retained by the plaintiff, said the findings of the internal review of patient data raise “a high level of concern regarding necessity of treatment provided,” according to case documents.

Medtronic declined to respond to ProPublica’s questions, citing the ongoing litigation. “These allegations are false and Medtronic is defending against these claims in court,” said Boua Xiong, a spokesperson for the company. Medtronic representative Kirk declined to respond to ProPublica’s request for comment.

The hospital investigation found that amputations increased sixfold in the same time frame as the procedures in question, according to internal emails, but made no conclusion about whether those two things were connected. ProPublica reached out to the VA to ask whether any patients had been harmed.

The VA is “conducting an extensive review of patient care” at the Kansas hospital, “including the number of devices used on patients – to make sure that Veterans were not harmed by any procedures,” press secretary Terrence Hayes said in a statement. So far, the VA’s investigation has found no “quality of care issues,” he said, and the investigation will continue “until every Veteran’s case has been reviewed.” (Read the full statement here.) Neither the department nor the hospital has taken formal action against the medical providers, Hayes said.

The medical group that had a contract with the VA for vascular interventions, Wichita Radiological Group, did not respond to ProPublica’s requests for comment, nor did the doctors named in the suit: Dr. Shaun Gonda, Dr. Bret Winblad, and Dr. Kermit Rust. It is unclear from the case documents which doctors conducted which procedures. Eric Barth, an attorney for the medical group, denied the allegations in recent legal filings, calling the claims “baseless” and the lawsuit a “witch hunt.”

The lawsuit comes amid growing concern about one of these procedures – atherectomies – after researchers and doctors have uncovered patterns of excessive and inappropriate use. Recent research has found that this procedure, a common but costly treatment to shave or laser plaque from blood vessels, is not more effective than cheaper alternatives and may even be associated with a higher risk of complications including amputation. In recent years, several doctors and clinics have been investigated for allegedly taking advantage of Medicare’s reimbursement rates, and one study found that many doctors are resorting to atherectomies in the earliest stages of peripheral artery disease, against best practices that urge noninvasive treatment.

“Atherectomy is important in certain settings. But it’s being used in a way that is entirely inappropriate and it’s largely driven by the incentive structure,” said Dr. Caitlin Hicks, the lead author of the study and an associate professor of surgery at Johns Hopkins University School of Medicine.

Although different payment structures govern the care of veterans, the whistleblower lawsuit alleges that outside physicians, paid hourly by the Dole VA, were motivated to conduct longer and more complex procedures that would earn them higher payment.

Under different circumstances, the patient in the procedure room on that summer day could have been done after 2 hours.

But, 150 minutes in, those Medtronic representatives were still texting. At that point, more than 15 of their vascular devices had been used, including stents, balloons, and those for atherectomy.

“Long case!” Kirk’s colleague texted. “Is it looking ok??”

“It is,” she said. “Thought we were done a few times! Now he’s going back in to cut again!”

A little while later, she texted: “....17!”

He texted back [with laughing emoticons].

Hospital leaders had been scrutinizing the use of these procedures at the Dole VA for years.

In 2017, shortly after Rick Ament was hired to lead the facility, he noticed something was amiss. While the longtime hospital administrator was poring over the finances, he was alarmed to discover that the relatively small Dole VA had one of the most expensive cardiac programs in the country. As Ament dug deeper, he realized vascular interventions were the reason.

“It just did not make sense that the acuity level of our patients would generate such extreme cost variances from the norm,” he testified in December, in a deposition for the whistleblower case. “It was so significant, we needed to get to the bottom of it.”

Ament, a second generation Air Force veteran, quietly assembled a task force to investigate why the facility had purchased so many medical devices for these procedures. After they examined inventory records, calculating the total number of medical devices and the cost of devices per patient, they grew concerned.

“We were more expensive than, I believe it was, the top 10 hospitals in the VA combined,” he said. “My feeling was that we either had very, very bad providers or we had product walking out the door.”

Ament enlisted experts from other VA hospitals to help his team investigate, including an administrative officer who could understand finances and a respected interventional radiologist who could examine records. The task force gathered a list of patients from 2016 to 2018, according to internal emails, and analyzed their medical charts.

According to internal VA documents released through the whistleblower suit, the review found a number of clinical failings: Evidence-based medicine had not been followed in the majority of cases reviewed. Procedures were over-aggressive, treating lesions that should have been left alone. And there was a total disregard for established best practices for treating peripheral artery disease.

One of the experts on the investigative team explained to Ament that while it was not uncommon for doctors to use a couple of devices in one intervention, the total number of devices in many of the procedures at his facility went into the double digits, sometimes five times the expected amount.

In one encounter, a doctor deployed 33 devices in one procedure – 3 atherectomy devices, 9 stents, and 21 balloons.

This use of devices was exorbitant, Ament came to understand. “I want to say the term ‘egregious’ was used,” he testified. “It was kind of like validation, but I really wish I was wrong.”

“Did it make you concerned for patient care?” a lawyer asked during the deposition.

“It did,” Ament replied.

A member of his task force pulled data for veterans who had leg amputations due to vascular disease. Over 5 years, the number of veterans who had amputations increased, from about 6 in 2013 to 38 in 2018, according to internal emails released in the suit. The VA did not respond to ProPublica’s questions about the rise in amputations or whether it was due to complications from the procedures.

Even though Ament testified in December 2022 that he became aware of the excessive use of devices during his investigation that began about 5 years ago, neither he nor the VA have publicly acknowledged these findings outside of the lawsuit. It is unclear whether VA representatives informed the patients whose records were reviewed about their findings. ProPublica reached out to more than half a dozen veteran community groups in the Wichita area and none were aware of the investigation nor the allegations of overuse of vascular procedures at the facility.

The VA says that if its ongoing review finds instances of substandard care, it will reach out to affected patients and inform them about possible complications and benefits they may be entitled to. The press secretary said the review will take several months. Ament declined to respond to ProPublica’s questions, citing the ongoing case.

In 2018, Ament turned over his findings to the criminal division of the VA’s Office of Inspector General. He also shut down interventional radiology procedures at the facility’s catheter lab.

Federal agents separately opened an investigation into the same unit in the facility, looking into allegations of kickbacks.

More than 40 pages of expense reports from Medtronic, revealed in the whistleblower case, show sales representatives treating Dole health care workers to hundreds of meals over several years – lunches at Dempsey’s Biscuit Co.; business meals at the Scotch & Sirloin steakhouse; dinner at Chester’s Chophouse & Wine Bar, price per attendee: $122.39.

Federal agents obtained the receipts.

“Robert J. Dole VAMC employees may have received improper gratuities, in the forms of paid lunches, dinners, etc., from sales representatives from Medtronic,” Nathen Howard, a special agent in the VA OIG, wrote in an investigation memo from February 2019.

This kind of relationship could violate VA policy, which forbids federal employees from receiving any gifts, including meals, from people who do business or seek to do business with a federal institution. For health care workers, violating this policy could have serious implications for patients. Numerous studies have shown that even modest industry-sponsored gifts, including meals, may influence prescribing or treatment behavior of health care professionals.

The agents opened their investigation into kickbacks at the Wichita facility in response to the whistleblower lawsuit, which was filed by Thomas Schroeder in 2017. The VA OIG would not confirm or deny whether it was continuing to investigate kickbacks at the facility. The VA did not directly answer ProPublica’s questions about kickbacks at the Dole VA, but it said that every employee must complete an annual ethics training, which covers gift rules.

In recent years, Medtronic has settled a handful of other cases that have alleged kickbacks between company representatives and health care professionals.

In 2018, Medtronic’s subsidiary Covidien paid $13 million to settle claims with the U.S. Department of Justice that it paid kickbacks to health care institutions that used its mechanical blood clot devices. In 2019, the same subsidiary paid $17 million to resolve allegations that it provided in-kind marketing support to doctors using its vein products. And in 2020, Medtronic paid more than $8 million to settle claims that representatives had paid kickbacks to a neurosurgeon, including scores of lavish meals at a restaurant that the doctor owned, to induce him to purchase the company’s medication pumps.

Schroeder’s lawsuit is not the first time Medtronic’s vascular devices were named in an alleged kickback scheme. In early 2015, Medtronic acquired Covidien, and shortly after the merger, its subsidiary ev3 Inc. agreed to pay $1.25 million to resolve allegations that it had paid doctors who were “high volume users” of its atherectomy devices to act as evangelists for the company, and had provided physicians with company shares to participate in clinical trials for their tools.

The whistleblower in this earlier case, a former sales representative for the company, also alleged that the subsidiary was gaming Medicare’s payment system. Hospitals were often hesitant to conduct atherectomy procedures because of the low reimbursement rates. According to the suit, sales representatives encouraged doctors to admit patients for longer stays to reap greater reimbursements and make a profit, even though such stays were often not medically indicated.

“Medical device makers that try to boost their profits by causing patients to be admitted for unnecessary and expensive inpatient hospital stays will be held accountable,” special agent Thomas O’Donnell, from the Office of Inspector General at the U.S. Department of Health and Human Services, said in a press release for the settlement. “Both patients and taxpayers deserve to have medical decisions made based on what is medically appropriate.”

Medtronic spokesperson Xiong said that in each case, the company “cooperated fully with the DOJ to resolve its concerns and, where wrongdoing was found, took appropriate remedial action.”

Seton Hall Law School professor Jacob Elberg, a former assistant U.S. attorney for the District of New Jersey who led its health care and government fraud unit, is concerned by the frequency of such settlements in the last 2 decades. “There are, at this point, real questions as to whether the sanctions imposed by DOJ are sufficient to deter wrongdoing and to lead to meaningful change, especially within the medical device industry.”

Although the Department of Justice has declined to intervene in the lawsuit involving the Dole VA at this time, the case is ongoing and further depositions with Medtronic sales representatives and a former VA employee are scheduled for this month.

VA employees and doctors named in the suit declined to comment or did not respond to ProPublica’s questions about the alleged kickbacks and whether sales representatives may have influenced veterans’ treatment plans. In interviews with federal investigators, according to released transcripts, several of the employees who were questioned denied receiving frequent meals from sales representatives, contradicting Medtronic’s expense reports.

Their statements also stand in contrast to Medtronic representative Kari Kirk’s final text messages during that procedure in June 2017, which ultimately lasted more than 3 hours.

“Now u done??” her colleague asked.

“Just finished,” she texted. “Running to get them lunch!”

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

On June 14, 2017, just before noon, a doctor made an incision near a patient’s groin. Kari Kirk, a representative for the world’s largest medical device company, Medtronic, looked on and began texting her colleague a play-by-play.

“Fixing both legs from the ankles,” she wrote.

It was a fairly common procedure at the Robert J. Dole Veterans Affairs Medical Center in Wichita, Kansas, performed to treat blockages in the leg vessels.

Within reach were an array of Medtronic products: tubes with blades attached to shave hardened deposits off of artery walls; stents to widen blood vessels; balloons coated with therapeutic drugs.

Each time a doctor puts a foreign device in someone’s body, it carries a risk of complication, which can include clots or even require amputation. So medical experts, research and even Medtronic’s own device instructions urge doctors to use as few as are necessary.

But, as revealed in Kirk’s text messages, this doctor took an aggressive approach.

“Just used 12 [drug-coated balloons]!!” Kirk texted her colleague.

“Does that mean I owe u $$,” he responded.

“Thats what I’m thinking!!!” she said. “And now 14 balloons?!”

“but only one stent so far??”

“So far!”

As the texting continued, her colleague replied, “U are going to want to start going to the VA all the time.”

The messages, recently unsealed in an ongoing whistleblower lawsuit, give a window into the way money and medicine mingle in the booming business of peripheral artery disease, a condition that afflicts 6.5 million Americans over age 40 and is caused when fatty plaque builds up in arteries, blocking blood flow to the legs.

Representatives from companies are often present during vascular procedures to guide doctors on how to use their complex devices. This kind of access has the potential to influence treatment plans, as companies and their representatives profit when more of their product is used.

The suit, filed in 2017 by a sales representative for a competing medical device firm, alleges an illegal kickback scheme between Medtronic and hospital employees. According to the complaint and documents released in the suit, between 2011 and 2018, VA health care workers received steakhouse dinners, Apple electronics, and NASCAR tickets, and in turn, Medtronic secured a lucrative contract with the hospital. Meanwhile, the company’s representatives allegedly “groomed and trained” physicians at the facility, who then deployed the company’s devices even when it was not medically indicated.

Independently from the whistleblower suit, internal investigators at the Wichita facility have also examined the treatment patterns of its vascular patients in recent years and found numerous cases where medical devices were used excessively. While it’s not uncommon to deploy several devices, a medical expert on the investigation team found that the VA doctors sometimes used more than 15 at a time – one used 33 – deviating from the standard of care.

“It is unconscionable – there can be no valid medically acceptable basis to cram so many devices into a human being,” wrote attorneys representing the whistleblower in legal filings from January 2023. “This is not medical treatment. This is abuse.”

Dr. Kim Hodgson, former president of the Society for Vascular Surgery and an expert retained by the plaintiff, said the findings of the internal review of patient data raise “a high level of concern regarding necessity of treatment provided,” according to case documents.

Medtronic declined to respond to ProPublica’s questions, citing the ongoing litigation. “These allegations are false and Medtronic is defending against these claims in court,” said Boua Xiong, a spokesperson for the company. Medtronic representative Kirk declined to respond to ProPublica’s request for comment.

The hospital investigation found that amputations increased sixfold in the same time frame as the procedures in question, according to internal emails, but made no conclusion about whether those two things were connected. ProPublica reached out to the VA to ask whether any patients had been harmed.

The VA is “conducting an extensive review of patient care” at the Kansas hospital, “including the number of devices used on patients – to make sure that Veterans were not harmed by any procedures,” press secretary Terrence Hayes said in a statement. So far, the VA’s investigation has found no “quality of care issues,” he said, and the investigation will continue “until every Veteran’s case has been reviewed.” (Read the full statement here.) Neither the department nor the hospital has taken formal action against the medical providers, Hayes said.

The medical group that had a contract with the VA for vascular interventions, Wichita Radiological Group, did not respond to ProPublica’s requests for comment, nor did the doctors named in the suit: Dr. Shaun Gonda, Dr. Bret Winblad, and Dr. Kermit Rust. It is unclear from the case documents which doctors conducted which procedures. Eric Barth, an attorney for the medical group, denied the allegations in recent legal filings, calling the claims “baseless” and the lawsuit a “witch hunt.”

The lawsuit comes amid growing concern about one of these procedures – atherectomies – after researchers and doctors have uncovered patterns of excessive and inappropriate use. Recent research has found that this procedure, a common but costly treatment to shave or laser plaque from blood vessels, is not more effective than cheaper alternatives and may even be associated with a higher risk of complications including amputation. In recent years, several doctors and clinics have been investigated for allegedly taking advantage of Medicare’s reimbursement rates, and one study found that many doctors are resorting to atherectomies in the earliest stages of peripheral artery disease, against best practices that urge noninvasive treatment.

“Atherectomy is important in certain settings. But it’s being used in a way that is entirely inappropriate and it’s largely driven by the incentive structure,” said Dr. Caitlin Hicks, the lead author of the study and an associate professor of surgery at Johns Hopkins University School of Medicine.

Although different payment structures govern the care of veterans, the whistleblower lawsuit alleges that outside physicians, paid hourly by the Dole VA, were motivated to conduct longer and more complex procedures that would earn them higher payment.

Under different circumstances, the patient in the procedure room on that summer day could have been done after 2 hours.

But, 150 minutes in, those Medtronic representatives were still texting. At that point, more than 15 of their vascular devices had been used, including stents, balloons, and those for atherectomy.

“Long case!” Kirk’s colleague texted. “Is it looking ok??”

“It is,” she said. “Thought we were done a few times! Now he’s going back in to cut again!”

A little while later, she texted: “....17!”

He texted back [with laughing emoticons].

Hospital leaders had been scrutinizing the use of these procedures at the Dole VA for years.

In 2017, shortly after Rick Ament was hired to lead the facility, he noticed something was amiss. While the longtime hospital administrator was poring over the finances, he was alarmed to discover that the relatively small Dole VA had one of the most expensive cardiac programs in the country. As Ament dug deeper, he realized vascular interventions were the reason.

“It just did not make sense that the acuity level of our patients would generate such extreme cost variances from the norm,” he testified in December, in a deposition for the whistleblower case. “It was so significant, we needed to get to the bottom of it.”

Ament, a second generation Air Force veteran, quietly assembled a task force to investigate why the facility had purchased so many medical devices for these procedures. After they examined inventory records, calculating the total number of medical devices and the cost of devices per patient, they grew concerned.

“We were more expensive than, I believe it was, the top 10 hospitals in the VA combined,” he said. “My feeling was that we either had very, very bad providers or we had product walking out the door.”

Ament enlisted experts from other VA hospitals to help his team investigate, including an administrative officer who could understand finances and a respected interventional radiologist who could examine records. The task force gathered a list of patients from 2016 to 2018, according to internal emails, and analyzed their medical charts.

According to internal VA documents released through the whistleblower suit, the review found a number of clinical failings: Evidence-based medicine had not been followed in the majority of cases reviewed. Procedures were over-aggressive, treating lesions that should have been left alone. And there was a total disregard for established best practices for treating peripheral artery disease.

One of the experts on the investigative team explained to Ament that while it was not uncommon for doctors to use a couple of devices in one intervention, the total number of devices in many of the procedures at his facility went into the double digits, sometimes five times the expected amount.

In one encounter, a doctor deployed 33 devices in one procedure – 3 atherectomy devices, 9 stents, and 21 balloons.

This use of devices was exorbitant, Ament came to understand. “I want to say the term ‘egregious’ was used,” he testified. “It was kind of like validation, but I really wish I was wrong.”

“Did it make you concerned for patient care?” a lawyer asked during the deposition.

“It did,” Ament replied.

A member of his task force pulled data for veterans who had leg amputations due to vascular disease. Over 5 years, the number of veterans who had amputations increased, from about 6 in 2013 to 38 in 2018, according to internal emails released in the suit. The VA did not respond to ProPublica’s questions about the rise in amputations or whether it was due to complications from the procedures.

Even though Ament testified in December 2022 that he became aware of the excessive use of devices during his investigation that began about 5 years ago, neither he nor the VA have publicly acknowledged these findings outside of the lawsuit. It is unclear whether VA representatives informed the patients whose records were reviewed about their findings. ProPublica reached out to more than half a dozen veteran community groups in the Wichita area and none were aware of the investigation nor the allegations of overuse of vascular procedures at the facility.

The VA says that if its ongoing review finds instances of substandard care, it will reach out to affected patients and inform them about possible complications and benefits they may be entitled to. The press secretary said the review will take several months. Ament declined to respond to ProPublica’s questions, citing the ongoing case.

In 2018, Ament turned over his findings to the criminal division of the VA’s Office of Inspector General. He also shut down interventional radiology procedures at the facility’s catheter lab.

Federal agents separately opened an investigation into the same unit in the facility, looking into allegations of kickbacks.

More than 40 pages of expense reports from Medtronic, revealed in the whistleblower case, show sales representatives treating Dole health care workers to hundreds of meals over several years – lunches at Dempsey’s Biscuit Co.; business meals at the Scotch & Sirloin steakhouse; dinner at Chester’s Chophouse & Wine Bar, price per attendee: $122.39.

Federal agents obtained the receipts.

“Robert J. Dole VAMC employees may have received improper gratuities, in the forms of paid lunches, dinners, etc., from sales representatives from Medtronic,” Nathen Howard, a special agent in the VA OIG, wrote in an investigation memo from February 2019.

This kind of relationship could violate VA policy, which forbids federal employees from receiving any gifts, including meals, from people who do business or seek to do business with a federal institution. For health care workers, violating this policy could have serious implications for patients. Numerous studies have shown that even modest industry-sponsored gifts, including meals, may influence prescribing or treatment behavior of health care professionals.

The agents opened their investigation into kickbacks at the Wichita facility in response to the whistleblower lawsuit, which was filed by Thomas Schroeder in 2017. The VA OIG would not confirm or deny whether it was continuing to investigate kickbacks at the facility. The VA did not directly answer ProPublica’s questions about kickbacks at the Dole VA, but it said that every employee must complete an annual ethics training, which covers gift rules.

In recent years, Medtronic has settled a handful of other cases that have alleged kickbacks between company representatives and health care professionals.

In 2018, Medtronic’s subsidiary Covidien paid $13 million to settle claims with the U.S. Department of Justice that it paid kickbacks to health care institutions that used its mechanical blood clot devices. In 2019, the same subsidiary paid $17 million to resolve allegations that it provided in-kind marketing support to doctors using its vein products. And in 2020, Medtronic paid more than $8 million to settle claims that representatives had paid kickbacks to a neurosurgeon, including scores of lavish meals at a restaurant that the doctor owned, to induce him to purchase the company’s medication pumps.

Schroeder’s lawsuit is not the first time Medtronic’s vascular devices were named in an alleged kickback scheme. In early 2015, Medtronic acquired Covidien, and shortly after the merger, its subsidiary ev3 Inc. agreed to pay $1.25 million to resolve allegations that it had paid doctors who were “high volume users” of its atherectomy devices to act as evangelists for the company, and had provided physicians with company shares to participate in clinical trials for their tools.

The whistleblower in this earlier case, a former sales representative for the company, also alleged that the subsidiary was gaming Medicare’s payment system. Hospitals were often hesitant to conduct atherectomy procedures because of the low reimbursement rates. According to the suit, sales representatives encouraged doctors to admit patients for longer stays to reap greater reimbursements and make a profit, even though such stays were often not medically indicated.

“Medical device makers that try to boost their profits by causing patients to be admitted for unnecessary and expensive inpatient hospital stays will be held accountable,” special agent Thomas O’Donnell, from the Office of Inspector General at the U.S. Department of Health and Human Services, said in a press release for the settlement. “Both patients and taxpayers deserve to have medical decisions made based on what is medically appropriate.”

Medtronic spokesperson Xiong said that in each case, the company “cooperated fully with the DOJ to resolve its concerns and, where wrongdoing was found, took appropriate remedial action.”

Seton Hall Law School professor Jacob Elberg, a former assistant U.S. attorney for the District of New Jersey who led its health care and government fraud unit, is concerned by the frequency of such settlements in the last 2 decades. “There are, at this point, real questions as to whether the sanctions imposed by DOJ are sufficient to deter wrongdoing and to lead to meaningful change, especially within the medical device industry.”

Although the Department of Justice has declined to intervene in the lawsuit involving the Dole VA at this time, the case is ongoing and further depositions with Medtronic sales representatives and a former VA employee are scheduled for this month.

VA employees and doctors named in the suit declined to comment or did not respond to ProPublica’s questions about the alleged kickbacks and whether sales representatives may have influenced veterans’ treatment plans. In interviews with federal investigators, according to released transcripts, several of the employees who were questioned denied receiving frequent meals from sales representatives, contradicting Medtronic’s expense reports.

Their statements also stand in contrast to Medtronic representative Kari Kirk’s final text messages during that procedure in June 2017, which ultimately lasted more than 3 hours.

“Now u done??” her colleague asked.

“Just finished,” she texted. “Running to get them lunch!”

This story was originally published on ProPublica. ProPublica is a nonprofit newsroom that investigates abuses of power. Sign up to receive their biggest stories as soon as they’re published.

Patients with a large cerebral infarction have better functional recovery when they receive endovascular therapy early on in addition to usual medical management, a new study shows.

The trial was stopped early because a planned interim analysis showed efficacy of endovascular therapy in this patient population.

Among patients in China with acute ischemic stroke and a large cerebral infarction, treatment with endovascular therapy within 24 hours after stroke onset “resulted in a better functional outcome at 3 months than medical management alone,” lead author Xiaochuan Huo, MD, PhD, associate chief physician, interventional neurology department, Beijing Tiantan Hospital, Capital Medical University, told this news organization.

“This trial added important evidence for the benefits of endovascular therapy,” Dr. Huo added.

The findings were presented at the International Stroke Conference and were published online in The New England Journal of Medicine. The conference was presented by the American Stroke Association, a division of the American Heart Association.

Will change practice

Commenting on the results, Tudor G. Jovin, MD, professor and chair, department of neurology, Cooper Medical School of Rowan University, Camden, N.J., said he has “little doubt” this study will change practice.

Despite previous studies showing signals of benefit from thrombectomy for patients with large-core infarcts, and some even finding a large treatment effect, “somehow the world didn’t register this,” said Dr. Jovin.

“The stroke community was perhaps reluctant to accept these signals that were there in plain sight because we have been primed for such a long time that reperfusing large infarcts was, if not detrimental, not beneficial.”

But this study, along with another study showing similar results, SELECT 2, which was also presented at this meeting and was published in the same issue of NEJM, provide “overwhelming proof” and “have finally made the community aware,” said Dr. Jovin. “This is sort of a wake-up call to say, ‘Hey, this is real; patients with large infarcts also benefit from thrombectomy.’ “

This new research suggests it’s not necessary to learn the infarct size, at least in the early time window, and doing so just wastes precious time, added Dr. Jovin.

The impact of thrombectomy on patients with “super large infarcts” is still not clear, although these are “extremely rare” in the early time window, perhaps representing only about 1% of patients, said Dr. Jovin.

The increased rate of hemorrhages in study patients receiving thrombectomy “is the price you pay” for the benefits, he said. He noted that this is not any different from the situation with tissue plasminogen activator (tPA), which is routinely used because the benefits far outweigh the risks.
 

ANGEL-ASPECT

As patients with large infarctions are generally excluded from studies of thrombectomy, it’s been unclear whether they benefit from this therapy, the researchers noted.

The multicenter Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) trial included 455 adult patients (median age, 68 years; 38.7% women) who had a large infarct core caused by acute large-vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score [ASPECTS] 3-5 without core volume limitations or ASPECTS 0–2 with core volume between 70 and 100 mL).

Study participants had to have a score of 6-30 on the National Institutes of Health Stroke Scale (NIHSS) and a retrospectively determined prestroke score of 0 or 1 on the Modified Rankin Scale (mRS).

The median baseline NIHSS score of study patients was 16, the median ASPECTS was 3, and the median infarct-core volume was 62 mL.

Researchers randomly assigned patients to undergo either medical management alone or medical management as well as endovascular therapy. Medical management included intravenous (IV) thrombolysis for those who were eligible.

IV thrombolysis was administered before thrombectomy for about 28% of patients in each group. Some 78.7% of all patients arrived at the hospital outside the typical 4.5-hour window and were ineligible for thrombolysis.

A greater percentage of patients in the endovascular therapy group was receiving antihypertensive medications (83.0%) than in the medical management alone group (54.0%). About 20% of patients in each group were taking an anticoagulant medication.

When the trial was halted, outcome data were available for 336 patients. An additional 120 patients had undergone randomization, and 455 had completed 90 days of follow-up.
 

Better functional outcome

The primary outcome was the score on the mRS at 90 days. Results showed a shift in the distribution of scores on the mRS at 90 days toward better outcomes favoring endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval [CI], 1.11-1.69; P = .004).

The efficacy of endovascular therapy with respect to the primary outcome was similar across predefined subgroups and across all trial sites. However, the trial was not powered to allow definite conclusions based on the results of subgroup analyses.

Although patients with an ASPECT score of 0-2 (indicating very large infarct cores) are considered unlikely to benefit from endovascular treatment, the researchers did find some signals of gain for these patients.

“Although no conclusions can be drawn because the trial was not powered for this analysis and the confidence interval for the odds ratio between the trial groups included 1, there may have been a benefit with endovascular therapy in this subgroup,” the authors wrote. “More trials are warranted to determine if this benefit is valid.”

As for secondary outcomes, the percentage of patients with a score of 0-2 on the mRS at 90 days was 30.0% in the endovascular therapy group and 11.6% in the medical management group (relative risk [RR], 2.62; 95% CI, 1.69-4.06).

The percentage of patients with a score of 0-3 on the mRS at 90 days was 47.0% in the endovascular therapy group and 33.3% in the medical management group (RR, 1.50; 95% CI, 1.17-1.91).

The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours, which occurred in 6.1% of the endovascular therapy group, compared to 2.7% in the medical management group (RR, 2.07; 95% CI, 0.79-5.41; P = .12)

Mortality within 90 days was 21.7% in the endovascular therapy group and 20.0% in the medical management group. Other serious adverse events occurred in 40.0% in the endovascular therapy group and 38.2% in the medical management group (P = .70).

The percentage of patients receiving IV thrombolysis was relatively low, which may have affected outcomes in the medical management group. Another potential limitation was that urokinase rather than alteplase, which is probably more effective, was used for thrombolysis in a small percentage of patients.

Further, the study did not include patients older than 80 years or those with an ASPECT value greater than 5 and infarct core volume of 70-100 mL, and it included only Chinese patients, so the results may not be generalizable, the researchers noted.

These findings will likely change clinical practice, said Dr. Huo, who noted that the current guideline doesn’t provide “a high-level recommendation” for [endovascular therapy] in patients with a low ASPECT score.

“These new results will change the guideline” to suggest endovascular therapy for large-core patients, he said.
 

Welcome news

An accompanying editorial by Pierre Fayad, MD, department of neurological sciences, division of vascular neurology and stroke, University of Nebraska Medical Center, Omaha, welcomed results from this and other recent related studies.

From these new results, “it is reasonable to suggest that endovascular thrombectomy be offered to patients with large strokes” if they arrive in a timely fashion at a center capable of performing the procedure and have an ASPECT value of 3-5 or an ischemic-core volume of 50 mL or greater, he wrote.

“The improved chance of independent walking and the ability to perform other daily activities in patients with the most severe strokes is welcome news for patients and for the field of stroke treatment.”

The study received funding from Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology. Dr. Huo and Dr. Jovin report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with a large cerebral infarction have better functional recovery when they receive endovascular therapy early on in addition to usual medical management, a new study shows.

The trial was stopped early because a planned interim analysis showed efficacy of endovascular therapy in this patient population.

Among patients in China with acute ischemic stroke and a large cerebral infarction, treatment with endovascular therapy within 24 hours after stroke onset “resulted in a better functional outcome at 3 months than medical management alone,” lead author Xiaochuan Huo, MD, PhD, associate chief physician, interventional neurology department, Beijing Tiantan Hospital, Capital Medical University, told this news organization.

“This trial added important evidence for the benefits of endovascular therapy,” Dr. Huo added.

The findings were presented at the International Stroke Conference and were published online in The New England Journal of Medicine. The conference was presented by the American Stroke Association, a division of the American Heart Association.

Will change practice

Commenting on the results, Tudor G. Jovin, MD, professor and chair, department of neurology, Cooper Medical School of Rowan University, Camden, N.J., said he has “little doubt” this study will change practice.

Despite previous studies showing signals of benefit from thrombectomy for patients with large-core infarcts, and some even finding a large treatment effect, “somehow the world didn’t register this,” said Dr. Jovin.

“The stroke community was perhaps reluctant to accept these signals that were there in plain sight because we have been primed for such a long time that reperfusing large infarcts was, if not detrimental, not beneficial.”

But this study, along with another study showing similar results, SELECT 2, which was also presented at this meeting and was published in the same issue of NEJM, provide “overwhelming proof” and “have finally made the community aware,” said Dr. Jovin. “This is sort of a wake-up call to say, ‘Hey, this is real; patients with large infarcts also benefit from thrombectomy.’ “

This new research suggests it’s not necessary to learn the infarct size, at least in the early time window, and doing so just wastes precious time, added Dr. Jovin.

The impact of thrombectomy on patients with “super large infarcts” is still not clear, although these are “extremely rare” in the early time window, perhaps representing only about 1% of patients, said Dr. Jovin.

The increased rate of hemorrhages in study patients receiving thrombectomy “is the price you pay” for the benefits, he said. He noted that this is not any different from the situation with tissue plasminogen activator (tPA), which is routinely used because the benefits far outweigh the risks.
 

ANGEL-ASPECT

As patients with large infarctions are generally excluded from studies of thrombectomy, it’s been unclear whether they benefit from this therapy, the researchers noted.

The multicenter Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) trial included 455 adult patients (median age, 68 years; 38.7% women) who had a large infarct core caused by acute large-vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score [ASPECTS] 3-5 without core volume limitations or ASPECTS 0–2 with core volume between 70 and 100 mL).

Study participants had to have a score of 6-30 on the National Institutes of Health Stroke Scale (NIHSS) and a retrospectively determined prestroke score of 0 or 1 on the Modified Rankin Scale (mRS).

The median baseline NIHSS score of study patients was 16, the median ASPECTS was 3, and the median infarct-core volume was 62 mL.

Researchers randomly assigned patients to undergo either medical management alone or medical management as well as endovascular therapy. Medical management included intravenous (IV) thrombolysis for those who were eligible.

IV thrombolysis was administered before thrombectomy for about 28% of patients in each group. Some 78.7% of all patients arrived at the hospital outside the typical 4.5-hour window and were ineligible for thrombolysis.

A greater percentage of patients in the endovascular therapy group was receiving antihypertensive medications (83.0%) than in the medical management alone group (54.0%). About 20% of patients in each group were taking an anticoagulant medication.

When the trial was halted, outcome data were available for 336 patients. An additional 120 patients had undergone randomization, and 455 had completed 90 days of follow-up.
 

Better functional outcome

The primary outcome was the score on the mRS at 90 days. Results showed a shift in the distribution of scores on the mRS at 90 days toward better outcomes favoring endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval [CI], 1.11-1.69; P = .004).

The efficacy of endovascular therapy with respect to the primary outcome was similar across predefined subgroups and across all trial sites. However, the trial was not powered to allow definite conclusions based on the results of subgroup analyses.

Although patients with an ASPECT score of 0-2 (indicating very large infarct cores) are considered unlikely to benefit from endovascular treatment, the researchers did find some signals of gain for these patients.

“Although no conclusions can be drawn because the trial was not powered for this analysis and the confidence interval for the odds ratio between the trial groups included 1, there may have been a benefit with endovascular therapy in this subgroup,” the authors wrote. “More trials are warranted to determine if this benefit is valid.”

As for secondary outcomes, the percentage of patients with a score of 0-2 on the mRS at 90 days was 30.0% in the endovascular therapy group and 11.6% in the medical management group (relative risk [RR], 2.62; 95% CI, 1.69-4.06).

The percentage of patients with a score of 0-3 on the mRS at 90 days was 47.0% in the endovascular therapy group and 33.3% in the medical management group (RR, 1.50; 95% CI, 1.17-1.91).

The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours, which occurred in 6.1% of the endovascular therapy group, compared to 2.7% in the medical management group (RR, 2.07; 95% CI, 0.79-5.41; P = .12)

Mortality within 90 days was 21.7% in the endovascular therapy group and 20.0% in the medical management group. Other serious adverse events occurred in 40.0% in the endovascular therapy group and 38.2% in the medical management group (P = .70).

The percentage of patients receiving IV thrombolysis was relatively low, which may have affected outcomes in the medical management group. Another potential limitation was that urokinase rather than alteplase, which is probably more effective, was used for thrombolysis in a small percentage of patients.

Further, the study did not include patients older than 80 years or those with an ASPECT value greater than 5 and infarct core volume of 70-100 mL, and it included only Chinese patients, so the results may not be generalizable, the researchers noted.

These findings will likely change clinical practice, said Dr. Huo, who noted that the current guideline doesn’t provide “a high-level recommendation” for [endovascular therapy] in patients with a low ASPECT score.

“These new results will change the guideline” to suggest endovascular therapy for large-core patients, he said.
 

Welcome news

An accompanying editorial by Pierre Fayad, MD, department of neurological sciences, division of vascular neurology and stroke, University of Nebraska Medical Center, Omaha, welcomed results from this and other recent related studies.

From these new results, “it is reasonable to suggest that endovascular thrombectomy be offered to patients with large strokes” if they arrive in a timely fashion at a center capable of performing the procedure and have an ASPECT value of 3-5 or an ischemic-core volume of 50 mL or greater, he wrote.

“The improved chance of independent walking and the ability to perform other daily activities in patients with the most severe strokes is welcome news for patients and for the field of stroke treatment.”

The study received funding from Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology. Dr. Huo and Dr. Jovin report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Patients with a large cerebral infarction have better functional recovery when they receive endovascular therapy early on in addition to usual medical management, a new study shows.

The trial was stopped early because a planned interim analysis showed efficacy of endovascular therapy in this patient population.

Among patients in China with acute ischemic stroke and a large cerebral infarction, treatment with endovascular therapy within 24 hours after stroke onset “resulted in a better functional outcome at 3 months than medical management alone,” lead author Xiaochuan Huo, MD, PhD, associate chief physician, interventional neurology department, Beijing Tiantan Hospital, Capital Medical University, told this news organization.

“This trial added important evidence for the benefits of endovascular therapy,” Dr. Huo added.

The findings were presented at the International Stroke Conference and were published online in The New England Journal of Medicine. The conference was presented by the American Stroke Association, a division of the American Heart Association.

Will change practice

Commenting on the results, Tudor G. Jovin, MD, professor and chair, department of neurology, Cooper Medical School of Rowan University, Camden, N.J., said he has “little doubt” this study will change practice.

Despite previous studies showing signals of benefit from thrombectomy for patients with large-core infarcts, and some even finding a large treatment effect, “somehow the world didn’t register this,” said Dr. Jovin.

“The stroke community was perhaps reluctant to accept these signals that were there in plain sight because we have been primed for such a long time that reperfusing large infarcts was, if not detrimental, not beneficial.”

But this study, along with another study showing similar results, SELECT 2, which was also presented at this meeting and was published in the same issue of NEJM, provide “overwhelming proof” and “have finally made the community aware,” said Dr. Jovin. “This is sort of a wake-up call to say, ‘Hey, this is real; patients with large infarcts also benefit from thrombectomy.’ “

This new research suggests it’s not necessary to learn the infarct size, at least in the early time window, and doing so just wastes precious time, added Dr. Jovin.

The impact of thrombectomy on patients with “super large infarcts” is still not clear, although these are “extremely rare” in the early time window, perhaps representing only about 1% of patients, said Dr. Jovin.

The increased rate of hemorrhages in study patients receiving thrombectomy “is the price you pay” for the benefits, he said. He noted that this is not any different from the situation with tissue plasminogen activator (tPA), which is routinely used because the benefits far outweigh the risks.
 

ANGEL-ASPECT

As patients with large infarctions are generally excluded from studies of thrombectomy, it’s been unclear whether they benefit from this therapy, the researchers noted.

The multicenter Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core (ANGEL-ASPECT) trial included 455 adult patients (median age, 68 years; 38.7% women) who had a large infarct core caused by acute large-vessel occlusion in the anterior circulation (Alberta Stroke Program Early CT Score [ASPECTS] 3-5 without core volume limitations or ASPECTS 0–2 with core volume between 70 and 100 mL).

Study participants had to have a score of 6-30 on the National Institutes of Health Stroke Scale (NIHSS) and a retrospectively determined prestroke score of 0 or 1 on the Modified Rankin Scale (mRS).

The median baseline NIHSS score of study patients was 16, the median ASPECTS was 3, and the median infarct-core volume was 62 mL.

Researchers randomly assigned patients to undergo either medical management alone or medical management as well as endovascular therapy. Medical management included intravenous (IV) thrombolysis for those who were eligible.

IV thrombolysis was administered before thrombectomy for about 28% of patients in each group. Some 78.7% of all patients arrived at the hospital outside the typical 4.5-hour window and were ineligible for thrombolysis.

A greater percentage of patients in the endovascular therapy group was receiving antihypertensive medications (83.0%) than in the medical management alone group (54.0%). About 20% of patients in each group were taking an anticoagulant medication.

When the trial was halted, outcome data were available for 336 patients. An additional 120 patients had undergone randomization, and 455 had completed 90 days of follow-up.
 

Better functional outcome

The primary outcome was the score on the mRS at 90 days. Results showed a shift in the distribution of scores on the mRS at 90 days toward better outcomes favoring endovascular therapy over medical management alone (generalized odds ratio, 1.37; 95% confidence interval [CI], 1.11-1.69; P = .004).

The efficacy of endovascular therapy with respect to the primary outcome was similar across predefined subgroups and across all trial sites. However, the trial was not powered to allow definite conclusions based on the results of subgroup analyses.

Although patients with an ASPECT score of 0-2 (indicating very large infarct cores) are considered unlikely to benefit from endovascular treatment, the researchers did find some signals of gain for these patients.

“Although no conclusions can be drawn because the trial was not powered for this analysis and the confidence interval for the odds ratio between the trial groups included 1, there may have been a benefit with endovascular therapy in this subgroup,” the authors wrote. “More trials are warranted to determine if this benefit is valid.”

As for secondary outcomes, the percentage of patients with a score of 0-2 on the mRS at 90 days was 30.0% in the endovascular therapy group and 11.6% in the medical management group (relative risk [RR], 2.62; 95% CI, 1.69-4.06).

The percentage of patients with a score of 0-3 on the mRS at 90 days was 47.0% in the endovascular therapy group and 33.3% in the medical management group (RR, 1.50; 95% CI, 1.17-1.91).

The primary safety outcome was symptomatic intracranial hemorrhage within 48 hours, which occurred in 6.1% of the endovascular therapy group, compared to 2.7% in the medical management group (RR, 2.07; 95% CI, 0.79-5.41; P = .12)

Mortality within 90 days was 21.7% in the endovascular therapy group and 20.0% in the medical management group. Other serious adverse events occurred in 40.0% in the endovascular therapy group and 38.2% in the medical management group (P = .70).

The percentage of patients receiving IV thrombolysis was relatively low, which may have affected outcomes in the medical management group. Another potential limitation was that urokinase rather than alteplase, which is probably more effective, was used for thrombolysis in a small percentage of patients.

Further, the study did not include patients older than 80 years or those with an ASPECT value greater than 5 and infarct core volume of 70-100 mL, and it included only Chinese patients, so the results may not be generalizable, the researchers noted.

These findings will likely change clinical practice, said Dr. Huo, who noted that the current guideline doesn’t provide “a high-level recommendation” for [endovascular therapy] in patients with a low ASPECT score.

“These new results will change the guideline” to suggest endovascular therapy for large-core patients, he said.
 

Welcome news

An accompanying editorial by Pierre Fayad, MD, department of neurological sciences, division of vascular neurology and stroke, University of Nebraska Medical Center, Omaha, welcomed results from this and other recent related studies.

From these new results, “it is reasonable to suggest that endovascular thrombectomy be offered to patients with large strokes” if they arrive in a timely fashion at a center capable of performing the procedure and have an ASPECT value of 3-5 or an ischemic-core volume of 50 mL or greater, he wrote.

“The improved chance of independent walking and the ability to perform other daily activities in patients with the most severe strokes is welcome news for patients and for the field of stroke treatment.”

The study received funding from Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology. Dr. Huo and Dr. Jovin report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In patients with acute ischemic stroke who have not received thrombolysis or thrombectomy, early antihypertensive treatment compared with delayed antihypertensive treatment did not reduce the likelihood of death and major disability at 3 months in the CATIS-2 trial.

The trial was presented by Liping Liu, MD, Beijing Tiantan Hospital, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Antihypertensive treatment can be delayed for at least 7 days following ischemic stroke onset, unless there are severe acute comorbidities that demand emergency blood pressure reduction to prevent serious complications,” Dr. Liu concluded.

But he acknowledged that the optimal BP management strategy in these patients remains uncertain and should be the focus of future research.

Discussing the trial at an ISC 2023 Highlights session, Lauren Sansing, MD, Yale University, New Haven, Conn., and ISC program vice chair, said: “These results seem to support waiting for a week or so before treating blood pressure in these patients.”

But Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and ISC program chair, countered: “To me, it’s kind of a neutral result, so what I take home from this is that you don’t necessarily have to wait.”

Dr. Jovin continued: “We used to think that it was mandatory not to treat blood pressure early because of the risk of deceasing the perfusion pressure, but this trial suggests the effects are neutral and there is probably as much benefit from lowering blood pressure for other reasons that offsets the potential harm.

“I think these are good data to rely on when we make these kinds of treatment decisions. Personally, I am a bit more aggressive with early blood pressure management and it’s good to see that you don’t get punished for that,” he added.

In his presentation, Dr. Liu explained that increased BP is common in acute stroke and is strongly associated with poor functional outcome and recurrence of ischemic stroke, but the optimal blood pressure management strategy in acute ischemic stroke remains controversial.

In the first CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke), which compared antihypertensive treatment within 48 hours of stroke onset with no antihypertensive treatment in ischemic stroke patients not receiving thrombolysis, the main results suggested that BP reduction with antihypertensive medications did not reduce the likelihood of death and major disability at 14 days or hospital discharge. But a subgroup analysis found that initiating antihypertensive treatment between 24 and 48 hours of stroke onset showed a beneficial effect on reducing death or major disability.

Current AHA/ASA guidelines suggest that, in patients with BP greater than 220/120 mm Hg who have not received thrombolysis or thrombectomy and have no comorbid conditions requiring urgent antihypertensive treatment, the benefit of initiating or reinitiating antihypertensive treatment within the first 48-72 hours is uncertain, although the guidelines say it might be reasonable to lower BP by around 15% during the first 24 hours after stroke onset, Dr. Liu noted.

The CATIS-2 trial was a multicenter, randomized, open-label, blinded-endpoints trial conducted at 106 centers in China that enrolled 4810 patients within 24-48 hours of onset of acute ischemic stroke who had elevated BP. Patients had not received thrombolytic therapy or mechanical thrombectomy.

Patients were randomly assigned to early antihypertensive therapy (initiated after randomization and aiming for a 10%-20% reduction in systolic BP) or delayed antihypertensive therapy (restarted antihypertensive therapy on day 8 of randomization, aiming for a BP of < 140/90 mm Hg).

The median age of the patients was 64 years, 65% were male, 80% had a history of hypertension, and the median National Institutes of Health Stroke Scale score was 3. Baseline BP averaged 163/92 mm Hg in both groups. The median time from stroke onset to antihypertensive treatment was 1.5 days in the early group and 8.5 days in the delayed group.

BP results showed that, at 24 hours after randomization, mean systolic pressure was reduced by 16.4 mm Hg (9.7%) in the early-treatment group and by 8.6 mm Hg (4.9%) in the delayed-treatment group (difference, –7.8 mm Hg; P < .0001).

At day 7, mean systolic pressure was 139.1 mm Hg in the early-treatment group, compared with 150.9 mm Hg in the delayed-treatment group, with a net difference in systolic BP of –11.9 mm Hg (P < .0001).

The primary outcome was the composite of death and major disability (modified Rankin Scale ≥ 3) at 3 months. This did not differ between the groups, occurring in 12.1% in the early antihypertensive treatment group versus 10.5% in the delayed antihypertensive treatment group (risk ratio, 1.15; P = .08).

There was also no difference in the major secondary outcome of shift in scores of mRS at 3 months, with a common odds ratio of 1.05 (95% confidence interval, 0.95-1.17).

There was no interaction with the composite outcome of death or major disability at 90 days in the prespecified subgroups.

Dr. Liu pointed out several limitations of the study. These included an observed primary outcome rate substantially lower than expected; the BP reduction seen within the first 7 days in the early-treatment group was moderate; and the results of the study cannot be applied to patients treated with thrombolysis or thrombectomy.

Dr. Liu has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In patients with acute ischemic stroke who have not received thrombolysis or thrombectomy, early antihypertensive treatment compared with delayed antihypertensive treatment did not reduce the likelihood of death and major disability at 3 months in the CATIS-2 trial.

The trial was presented by Liping Liu, MD, Beijing Tiantan Hospital, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Antihypertensive treatment can be delayed for at least 7 days following ischemic stroke onset, unless there are severe acute comorbidities that demand emergency blood pressure reduction to prevent serious complications,” Dr. Liu concluded.

But he acknowledged that the optimal BP management strategy in these patients remains uncertain and should be the focus of future research.

Discussing the trial at an ISC 2023 Highlights session, Lauren Sansing, MD, Yale University, New Haven, Conn., and ISC program vice chair, said: “These results seem to support waiting for a week or so before treating blood pressure in these patients.”

But Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and ISC program chair, countered: “To me, it’s kind of a neutral result, so what I take home from this is that you don’t necessarily have to wait.”

Dr. Jovin continued: “We used to think that it was mandatory not to treat blood pressure early because of the risk of deceasing the perfusion pressure, but this trial suggests the effects are neutral and there is probably as much benefit from lowering blood pressure for other reasons that offsets the potential harm.

“I think these are good data to rely on when we make these kinds of treatment decisions. Personally, I am a bit more aggressive with early blood pressure management and it’s good to see that you don’t get punished for that,” he added.

In his presentation, Dr. Liu explained that increased BP is common in acute stroke and is strongly associated with poor functional outcome and recurrence of ischemic stroke, but the optimal blood pressure management strategy in acute ischemic stroke remains controversial.

In the first CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke), which compared antihypertensive treatment within 48 hours of stroke onset with no antihypertensive treatment in ischemic stroke patients not receiving thrombolysis, the main results suggested that BP reduction with antihypertensive medications did not reduce the likelihood of death and major disability at 14 days or hospital discharge. But a subgroup analysis found that initiating antihypertensive treatment between 24 and 48 hours of stroke onset showed a beneficial effect on reducing death or major disability.

Current AHA/ASA guidelines suggest that, in patients with BP greater than 220/120 mm Hg who have not received thrombolysis or thrombectomy and have no comorbid conditions requiring urgent antihypertensive treatment, the benefit of initiating or reinitiating antihypertensive treatment within the first 48-72 hours is uncertain, although the guidelines say it might be reasonable to lower BP by around 15% during the first 24 hours after stroke onset, Dr. Liu noted.

The CATIS-2 trial was a multicenter, randomized, open-label, blinded-endpoints trial conducted at 106 centers in China that enrolled 4810 patients within 24-48 hours of onset of acute ischemic stroke who had elevated BP. Patients had not received thrombolytic therapy or mechanical thrombectomy.

Patients were randomly assigned to early antihypertensive therapy (initiated after randomization and aiming for a 10%-20% reduction in systolic BP) or delayed antihypertensive therapy (restarted antihypertensive therapy on day 8 of randomization, aiming for a BP of < 140/90 mm Hg).

The median age of the patients was 64 years, 65% were male, 80% had a history of hypertension, and the median National Institutes of Health Stroke Scale score was 3. Baseline BP averaged 163/92 mm Hg in both groups. The median time from stroke onset to antihypertensive treatment was 1.5 days in the early group and 8.5 days in the delayed group.

BP results showed that, at 24 hours after randomization, mean systolic pressure was reduced by 16.4 mm Hg (9.7%) in the early-treatment group and by 8.6 mm Hg (4.9%) in the delayed-treatment group (difference, –7.8 mm Hg; P < .0001).

At day 7, mean systolic pressure was 139.1 mm Hg in the early-treatment group, compared with 150.9 mm Hg in the delayed-treatment group, with a net difference in systolic BP of –11.9 mm Hg (P < .0001).

The primary outcome was the composite of death and major disability (modified Rankin Scale ≥ 3) at 3 months. This did not differ between the groups, occurring in 12.1% in the early antihypertensive treatment group versus 10.5% in the delayed antihypertensive treatment group (risk ratio, 1.15; P = .08).

There was also no difference in the major secondary outcome of shift in scores of mRS at 3 months, with a common odds ratio of 1.05 (95% confidence interval, 0.95-1.17).

There was no interaction with the composite outcome of death or major disability at 90 days in the prespecified subgroups.

Dr. Liu pointed out several limitations of the study. These included an observed primary outcome rate substantially lower than expected; the BP reduction seen within the first 7 days in the early-treatment group was moderate; and the results of the study cannot be applied to patients treated with thrombolysis or thrombectomy.

Dr. Liu has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In patients with acute ischemic stroke who have not received thrombolysis or thrombectomy, early antihypertensive treatment compared with delayed antihypertensive treatment did not reduce the likelihood of death and major disability at 3 months in the CATIS-2 trial.

The trial was presented by Liping Liu, MD, Beijing Tiantan Hospital, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Antihypertensive treatment can be delayed for at least 7 days following ischemic stroke onset, unless there are severe acute comorbidities that demand emergency blood pressure reduction to prevent serious complications,” Dr. Liu concluded.

But he acknowledged that the optimal BP management strategy in these patients remains uncertain and should be the focus of future research.

Discussing the trial at an ISC 2023 Highlights session, Lauren Sansing, MD, Yale University, New Haven, Conn., and ISC program vice chair, said: “These results seem to support waiting for a week or so before treating blood pressure in these patients.”

But Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., and ISC program chair, countered: “To me, it’s kind of a neutral result, so what I take home from this is that you don’t necessarily have to wait.”

Dr. Jovin continued: “We used to think that it was mandatory not to treat blood pressure early because of the risk of deceasing the perfusion pressure, but this trial suggests the effects are neutral and there is probably as much benefit from lowering blood pressure for other reasons that offsets the potential harm.

“I think these are good data to rely on when we make these kinds of treatment decisions. Personally, I am a bit more aggressive with early blood pressure management and it’s good to see that you don’t get punished for that,” he added.

In his presentation, Dr. Liu explained that increased BP is common in acute stroke and is strongly associated with poor functional outcome and recurrence of ischemic stroke, but the optimal blood pressure management strategy in acute ischemic stroke remains controversial.

In the first CATIS trial (China Antihypertensive Trial in Acute Ischemic Stroke), which compared antihypertensive treatment within 48 hours of stroke onset with no antihypertensive treatment in ischemic stroke patients not receiving thrombolysis, the main results suggested that BP reduction with antihypertensive medications did not reduce the likelihood of death and major disability at 14 days or hospital discharge. But a subgroup analysis found that initiating antihypertensive treatment between 24 and 48 hours of stroke onset showed a beneficial effect on reducing death or major disability.

Current AHA/ASA guidelines suggest that, in patients with BP greater than 220/120 mm Hg who have not received thrombolysis or thrombectomy and have no comorbid conditions requiring urgent antihypertensive treatment, the benefit of initiating or reinitiating antihypertensive treatment within the first 48-72 hours is uncertain, although the guidelines say it might be reasonable to lower BP by around 15% during the first 24 hours after stroke onset, Dr. Liu noted.

The CATIS-2 trial was a multicenter, randomized, open-label, blinded-endpoints trial conducted at 106 centers in China that enrolled 4810 patients within 24-48 hours of onset of acute ischemic stroke who had elevated BP. Patients had not received thrombolytic therapy or mechanical thrombectomy.

Patients were randomly assigned to early antihypertensive therapy (initiated after randomization and aiming for a 10%-20% reduction in systolic BP) or delayed antihypertensive therapy (restarted antihypertensive therapy on day 8 of randomization, aiming for a BP of < 140/90 mm Hg).

The median age of the patients was 64 years, 65% were male, 80% had a history of hypertension, and the median National Institutes of Health Stroke Scale score was 3. Baseline BP averaged 163/92 mm Hg in both groups. The median time from stroke onset to antihypertensive treatment was 1.5 days in the early group and 8.5 days in the delayed group.

BP results showed that, at 24 hours after randomization, mean systolic pressure was reduced by 16.4 mm Hg (9.7%) in the early-treatment group and by 8.6 mm Hg (4.9%) in the delayed-treatment group (difference, –7.8 mm Hg; P < .0001).

At day 7, mean systolic pressure was 139.1 mm Hg in the early-treatment group, compared with 150.9 mm Hg in the delayed-treatment group, with a net difference in systolic BP of –11.9 mm Hg (P < .0001).

The primary outcome was the composite of death and major disability (modified Rankin Scale ≥ 3) at 3 months. This did not differ between the groups, occurring in 12.1% in the early antihypertensive treatment group versus 10.5% in the delayed antihypertensive treatment group (risk ratio, 1.15; P = .08).

There was also no difference in the major secondary outcome of shift in scores of mRS at 3 months, with a common odds ratio of 1.05 (95% confidence interval, 0.95-1.17).

There was no interaction with the composite outcome of death or major disability at 90 days in the prespecified subgroups.

Dr. Liu pointed out several limitations of the study. These included an observed primary outcome rate substantially lower than expected; the BP reduction seen within the first 7 days in the early-treatment group was moderate; and the results of the study cannot be applied to patients treated with thrombolysis or thrombectomy.

Dr. Liu has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Among Chinese patients with minor nondisabling stroke who presented within 4.5 hours of symptom onset, dual antiplatelet treatment was noninferior to thrombolysis with intravenous alteplase with regard to functional outcome at 90 days in the ARAMIS trial.

The trial was presented by Thanh Nguyen, MD, Boston Medical Center, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Given the ease of administration, less intensive monitoring, low cost, and safety profile of dual antiplatelet therapy, the current findings support the use of dual antiplatelet in this population,” Dr. Nguyen concluded.

In a comment on the trial, Pooja Khatri, MD, professor of neurology at the University of Cincinnati, and lead investigator of the previous PRISMS study of tissue plasminogen activator (tPA) or alteplase in mild stroke, said the results reinforced the current recommendations of giving dual antiplatelet therapy but not alteplase to these patients.

Noting that the standard of care is now to give dual antiplatelet therapy to these patients, Dr. Khatri said: “These data reassure that this remains the right way to go.”

She added that her take-home message from the study would be: “Keep giving dual antiplatelet therapy, and we may be doing more harm than good with alteplase in this patient population.”

Introducing her presentation, Dr. Nguyen explained that mild ischemic stroke, defined as having a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less, comprises half of ischemic stroke patients in the United States. But the benefit of thrombolysis in patients with minor ischemic stroke that is not disabling is unknown.

A subgroup analysis of one of the major thrombolysis trials (IST-3) found that a higher proportion of patients with mild ischemic stroke who were treated within 3 hours of symptom onset were alive and independent at 6 months if they had been given thrombolysis (84%), compared to 65% in the control group who received standard medical treatment.

This led to the first randomized trial (PRISMS) dedicated to patients with mild nondisabling stroke, which found that alteplase given within 3 hours of symptom onset did not increase the likelihood of a good functional outcome at 90 days in comparison with single-agent aspirin. The study was unfortunately terminated early for administrative reasons, and no definitive conclusions could be drawn on the basis of these results, Dr. Nguyen reported.

In 2018, the American Heart Association/American Stroke Association guidelines indicated that for patients who present within 3 hours of symptom onset with mild ischemic stroke that was judged to be nondisabling, thrombolysis with intravenous alteplase could be considered, she noted.

In the meantime, dual antiplatelet therapy was shown to be safe and effective in the POINT and CHANCE trials in patients presenting with minor stroke within 12 or 24 hours, and the CHANCE trial also found a benefit in reducing recurrent stroke that was most effective in the first 2 weeks.

The current ARAMIS trial was therefore conducted to evaluate dual antiplatelet therapy in comparison with thrombolysis for patients with acute minor stroke (NIHSS 5 or less) who presented within 4.5 hours of symptom onset and were without clearly disabling deficit.

The trial was conducted in 38 hospitals in China and included 760 patients (median NIHSS score of 2) who were randomly assigned to receive intravenous alteplase at the standard dose of 0.9 mg/kg, followed by guideline-based antiplatelet treatment, or dual antiplatelet therapy (clopidogrel 300 mg plus 100 mg aspirin loading dose followed by 10 to 14 days of aspirin 100 mg and clopidogrel 75 mg).

The trial was designed to assess noninferiority of dual antiplatelet therapy to alteplase with noninferiority margin of –4.5%.

In the modified intention-to-treat analysis, which included 722 patients, the primary outcome (excellent functional outcome, defined as a Modified Rankin Scale score of 0 or 1 at 90 days) occurred in 93.8% of patients in the dual antiplatelet therapy group and in 91.4% of the alteplase group. This gave a difference of 2.4%, which fell within the limits for noninferiority (P = .0002 for noninferiority test).

“Therefore, this was a positive trial,” Dr. Nguyen stated.

About 20% of patients crossed over from the dual antiplatelet group to the thrombolysis group, and about 16% of patients crossed over from the thrombolysis group to the dual antiplatelet group. But a per-protocol and an “as treated” analysis showed results similar to those of the main intention-to-treat analysis.

Secondary outcomes were largely similar between the two groups other than early neurologic deterioration, which was less common in the dual antiplatelet therapy group.

In terms of safety, symptomatic intracranial hemorrhage occurred in 0.3% (1/369) in the dual antiplatelet group and in 0.9% (3/350) in the alteplase group, a nonsignificant difference.

Events of “any bleeding” occurred in more patients in the thrombolysis group (5.4%) than in the dual antiplatelet therapy group (1.6%), and this difference was significant (P = .01).

Subgroup analysis showed a trend toward benefit of alteplase for patients with higher NIHSS score at baseline (NIHSS > 3). Otherwise, the other subgroups looked similar to the main results.

Dr. Nguyen pointed out one limitation of the study – that dual antiplatelet therapy was updated to standard treatment in this target population in the 2019 AHA/ASA guidelines.

In her discussion of the study, Dr. Khatri suggested that the ARAMIS results were what might have been expected.

“Dual antiplatelet therapy is designed to prevent stroke. Even in the POINT trial, dual antiplatelet therapy showed no effect on 90-day functional outcome. It was really about prevention. The PRISMS trial suggested that alteplase was also unlikely to improve 90-day functional outcome in this population of patients with mild and not clearly disabling stroke. So, it is not surprising that dual antiplatelet therapy was noninferior to alteplase for 90-day functional outcome for both those reasons,” she explained.

“That being said, while designed as a noninferiority study, it is interesting to note that alteplase again showed no evidence of treatment effect compared to antiplatelet therapy, affirming what was observed in the prematurely terminated PRISMS trial,” Dr. Khatri added.

In a discussion of the study at an ISC 2023 highlights session, ISC program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “This is very important data and it’s actually the first completed trial that examines this question.”

But, he added, “I think we need to refine our knowledge about what a nondisabling stroke actually is. You could argue that every stroke is disabling. I think we need more clarity on this definition, as in practice, many clinicians still give tPA on account of these mild strokes still being disabling.”

The ARAMIS trial was funded by the National Key R&D Program of China and the Science and Technology Project Plan of Liaoning Province. Dr. Nguyen reports research support from Medtronic that was not related to the current study.

A version of this article first appeared on Medscape.com.

Among Chinese patients with minor nondisabling stroke who presented within 4.5 hours of symptom onset, dual antiplatelet treatment was noninferior to thrombolysis with intravenous alteplase with regard to functional outcome at 90 days in the ARAMIS trial.

The trial was presented by Thanh Nguyen, MD, Boston Medical Center, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Given the ease of administration, less intensive monitoring, low cost, and safety profile of dual antiplatelet therapy, the current findings support the use of dual antiplatelet in this population,” Dr. Nguyen concluded.

In a comment on the trial, Pooja Khatri, MD, professor of neurology at the University of Cincinnati, and lead investigator of the previous PRISMS study of tissue plasminogen activator (tPA) or alteplase in mild stroke, said the results reinforced the current recommendations of giving dual antiplatelet therapy but not alteplase to these patients.

Noting that the standard of care is now to give dual antiplatelet therapy to these patients, Dr. Khatri said: “These data reassure that this remains the right way to go.”

She added that her take-home message from the study would be: “Keep giving dual antiplatelet therapy, and we may be doing more harm than good with alteplase in this patient population.”

Introducing her presentation, Dr. Nguyen explained that mild ischemic stroke, defined as having a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less, comprises half of ischemic stroke patients in the United States. But the benefit of thrombolysis in patients with minor ischemic stroke that is not disabling is unknown.

A subgroup analysis of one of the major thrombolysis trials (IST-3) found that a higher proportion of patients with mild ischemic stroke who were treated within 3 hours of symptom onset were alive and independent at 6 months if they had been given thrombolysis (84%), compared to 65% in the control group who received standard medical treatment.

This led to the first randomized trial (PRISMS) dedicated to patients with mild nondisabling stroke, which found that alteplase given within 3 hours of symptom onset did not increase the likelihood of a good functional outcome at 90 days in comparison with single-agent aspirin. The study was unfortunately terminated early for administrative reasons, and no definitive conclusions could be drawn on the basis of these results, Dr. Nguyen reported.

In 2018, the American Heart Association/American Stroke Association guidelines indicated that for patients who present within 3 hours of symptom onset with mild ischemic stroke that was judged to be nondisabling, thrombolysis with intravenous alteplase could be considered, she noted.

In the meantime, dual antiplatelet therapy was shown to be safe and effective in the POINT and CHANCE trials in patients presenting with minor stroke within 12 or 24 hours, and the CHANCE trial also found a benefit in reducing recurrent stroke that was most effective in the first 2 weeks.

The current ARAMIS trial was therefore conducted to evaluate dual antiplatelet therapy in comparison with thrombolysis for patients with acute minor stroke (NIHSS 5 or less) who presented within 4.5 hours of symptom onset and were without clearly disabling deficit.

The trial was conducted in 38 hospitals in China and included 760 patients (median NIHSS score of 2) who were randomly assigned to receive intravenous alteplase at the standard dose of 0.9 mg/kg, followed by guideline-based antiplatelet treatment, or dual antiplatelet therapy (clopidogrel 300 mg plus 100 mg aspirin loading dose followed by 10 to 14 days of aspirin 100 mg and clopidogrel 75 mg).

The trial was designed to assess noninferiority of dual antiplatelet therapy to alteplase with noninferiority margin of –4.5%.

In the modified intention-to-treat analysis, which included 722 patients, the primary outcome (excellent functional outcome, defined as a Modified Rankin Scale score of 0 or 1 at 90 days) occurred in 93.8% of patients in the dual antiplatelet therapy group and in 91.4% of the alteplase group. This gave a difference of 2.4%, which fell within the limits for noninferiority (P = .0002 for noninferiority test).

“Therefore, this was a positive trial,” Dr. Nguyen stated.

About 20% of patients crossed over from the dual antiplatelet group to the thrombolysis group, and about 16% of patients crossed over from the thrombolysis group to the dual antiplatelet group. But a per-protocol and an “as treated” analysis showed results similar to those of the main intention-to-treat analysis.

Secondary outcomes were largely similar between the two groups other than early neurologic deterioration, which was less common in the dual antiplatelet therapy group.

In terms of safety, symptomatic intracranial hemorrhage occurred in 0.3% (1/369) in the dual antiplatelet group and in 0.9% (3/350) in the alteplase group, a nonsignificant difference.

Events of “any bleeding” occurred in more patients in the thrombolysis group (5.4%) than in the dual antiplatelet therapy group (1.6%), and this difference was significant (P = .01).

Subgroup analysis showed a trend toward benefit of alteplase for patients with higher NIHSS score at baseline (NIHSS > 3). Otherwise, the other subgroups looked similar to the main results.

Dr. Nguyen pointed out one limitation of the study – that dual antiplatelet therapy was updated to standard treatment in this target population in the 2019 AHA/ASA guidelines.

In her discussion of the study, Dr. Khatri suggested that the ARAMIS results were what might have been expected.

“Dual antiplatelet therapy is designed to prevent stroke. Even in the POINT trial, dual antiplatelet therapy showed no effect on 90-day functional outcome. It was really about prevention. The PRISMS trial suggested that alteplase was also unlikely to improve 90-day functional outcome in this population of patients with mild and not clearly disabling stroke. So, it is not surprising that dual antiplatelet therapy was noninferior to alteplase for 90-day functional outcome for both those reasons,” she explained.

“That being said, while designed as a noninferiority study, it is interesting to note that alteplase again showed no evidence of treatment effect compared to antiplatelet therapy, affirming what was observed in the prematurely terminated PRISMS trial,” Dr. Khatri added.

In a discussion of the study at an ISC 2023 highlights session, ISC program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “This is very important data and it’s actually the first completed trial that examines this question.”

But, he added, “I think we need to refine our knowledge about what a nondisabling stroke actually is. You could argue that every stroke is disabling. I think we need more clarity on this definition, as in practice, many clinicians still give tPA on account of these mild strokes still being disabling.”

The ARAMIS trial was funded by the National Key R&D Program of China and the Science and Technology Project Plan of Liaoning Province. Dr. Nguyen reports research support from Medtronic that was not related to the current study.

A version of this article first appeared on Medscape.com.

Among Chinese patients with minor nondisabling stroke who presented within 4.5 hours of symptom onset, dual antiplatelet treatment was noninferior to thrombolysis with intravenous alteplase with regard to functional outcome at 90 days in the ARAMIS trial.

The trial was presented by Thanh Nguyen, MD, Boston Medical Center, at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

“Given the ease of administration, less intensive monitoring, low cost, and safety profile of dual antiplatelet therapy, the current findings support the use of dual antiplatelet in this population,” Dr. Nguyen concluded.

In a comment on the trial, Pooja Khatri, MD, professor of neurology at the University of Cincinnati, and lead investigator of the previous PRISMS study of tissue plasminogen activator (tPA) or alteplase in mild stroke, said the results reinforced the current recommendations of giving dual antiplatelet therapy but not alteplase to these patients.

Noting that the standard of care is now to give dual antiplatelet therapy to these patients, Dr. Khatri said: “These data reassure that this remains the right way to go.”

She added that her take-home message from the study would be: “Keep giving dual antiplatelet therapy, and we may be doing more harm than good with alteplase in this patient population.”

Introducing her presentation, Dr. Nguyen explained that mild ischemic stroke, defined as having a National Institutes of Health Stroke Scale (NIHSS) score of 5 or less, comprises half of ischemic stroke patients in the United States. But the benefit of thrombolysis in patients with minor ischemic stroke that is not disabling is unknown.

A subgroup analysis of one of the major thrombolysis trials (IST-3) found that a higher proportion of patients with mild ischemic stroke who were treated within 3 hours of symptom onset were alive and independent at 6 months if they had been given thrombolysis (84%), compared to 65% in the control group who received standard medical treatment.

This led to the first randomized trial (PRISMS) dedicated to patients with mild nondisabling stroke, which found that alteplase given within 3 hours of symptom onset did not increase the likelihood of a good functional outcome at 90 days in comparison with single-agent aspirin. The study was unfortunately terminated early for administrative reasons, and no definitive conclusions could be drawn on the basis of these results, Dr. Nguyen reported.

In 2018, the American Heart Association/American Stroke Association guidelines indicated that for patients who present within 3 hours of symptom onset with mild ischemic stroke that was judged to be nondisabling, thrombolysis with intravenous alteplase could be considered, she noted.

In the meantime, dual antiplatelet therapy was shown to be safe and effective in the POINT and CHANCE trials in patients presenting with minor stroke within 12 or 24 hours, and the CHANCE trial also found a benefit in reducing recurrent stroke that was most effective in the first 2 weeks.

The current ARAMIS trial was therefore conducted to evaluate dual antiplatelet therapy in comparison with thrombolysis for patients with acute minor stroke (NIHSS 5 or less) who presented within 4.5 hours of symptom onset and were without clearly disabling deficit.

The trial was conducted in 38 hospitals in China and included 760 patients (median NIHSS score of 2) who were randomly assigned to receive intravenous alteplase at the standard dose of 0.9 mg/kg, followed by guideline-based antiplatelet treatment, or dual antiplatelet therapy (clopidogrel 300 mg plus 100 mg aspirin loading dose followed by 10 to 14 days of aspirin 100 mg and clopidogrel 75 mg).

The trial was designed to assess noninferiority of dual antiplatelet therapy to alteplase with noninferiority margin of –4.5%.

In the modified intention-to-treat analysis, which included 722 patients, the primary outcome (excellent functional outcome, defined as a Modified Rankin Scale score of 0 or 1 at 90 days) occurred in 93.8% of patients in the dual antiplatelet therapy group and in 91.4% of the alteplase group. This gave a difference of 2.4%, which fell within the limits for noninferiority (P = .0002 for noninferiority test).

“Therefore, this was a positive trial,” Dr. Nguyen stated.

About 20% of patients crossed over from the dual antiplatelet group to the thrombolysis group, and about 16% of patients crossed over from the thrombolysis group to the dual antiplatelet group. But a per-protocol and an “as treated” analysis showed results similar to those of the main intention-to-treat analysis.

Secondary outcomes were largely similar between the two groups other than early neurologic deterioration, which was less common in the dual antiplatelet therapy group.

In terms of safety, symptomatic intracranial hemorrhage occurred in 0.3% (1/369) in the dual antiplatelet group and in 0.9% (3/350) in the alteplase group, a nonsignificant difference.

Events of “any bleeding” occurred in more patients in the thrombolysis group (5.4%) than in the dual antiplatelet therapy group (1.6%), and this difference was significant (P = .01).

Subgroup analysis showed a trend toward benefit of alteplase for patients with higher NIHSS score at baseline (NIHSS > 3). Otherwise, the other subgroups looked similar to the main results.

Dr. Nguyen pointed out one limitation of the study – that dual antiplatelet therapy was updated to standard treatment in this target population in the 2019 AHA/ASA guidelines.

In her discussion of the study, Dr. Khatri suggested that the ARAMIS results were what might have been expected.

“Dual antiplatelet therapy is designed to prevent stroke. Even in the POINT trial, dual antiplatelet therapy showed no effect on 90-day functional outcome. It was really about prevention. The PRISMS trial suggested that alteplase was also unlikely to improve 90-day functional outcome in this population of patients with mild and not clearly disabling stroke. So, it is not surprising that dual antiplatelet therapy was noninferior to alteplase for 90-day functional outcome for both those reasons,” she explained.

“That being said, while designed as a noninferiority study, it is interesting to note that alteplase again showed no evidence of treatment effect compared to antiplatelet therapy, affirming what was observed in the prematurely terminated PRISMS trial,” Dr. Khatri added.

In a discussion of the study at an ISC 2023 highlights session, ISC program chair Tudor Jovin, MD, Cooper Neurological Institute, Cherry Hill, N.J., said: “This is very important data and it’s actually the first completed trial that examines this question.”

But, he added, “I think we need to refine our knowledge about what a nondisabling stroke actually is. You could argue that every stroke is disabling. I think we need more clarity on this definition, as in practice, many clinicians still give tPA on account of these mild strokes still being disabling.”

The ARAMIS trial was funded by the National Key R&D Program of China and the Science and Technology Project Plan of Liaoning Province. Dr. Nguyen reports research support from Medtronic that was not related to the current study.

A version of this article first appeared on Medscape.com.

Physicians routinely monitor cholesterol, blood pressure, and glucose levels to get a clearer picture of their patients’ overall health. But a group of experts argues that having an accurate read of a person’s ability to absorb oxygen during peak exertion – VO₂ max – is just as important.

Once the focus of cyclists and other elite athletes, VO₂ max has in recent years caught the attention of geriatricians, who have linked the measure to maximum functional capacity – an umbrella term for the body’s ability to perform aerobic exercise.

“Function is prognostic of mortality,” said Daniel E. Forman, MD, FAHA, FACC, professor of medicine and chair of the section of geriatric cardiology at the University of Pittsburgh Medical Center. “If you aren’t looking at that, you’re missing the boat.”

Although cardiopulmonary exercise testing (CPET) remains the gold standard for assessing VO₂ max, Dr. Forman said clinicians often overlook CPET because it is old.
 

Getting precise

As a person ages, the amount of physical activity needed to stay fit varies, depending on genes, health, and fitness history. Measuring VO₂ max can help doctors better prescribe physical activity, both with regard to specific exercises and for how long, Claudio Gil Araújo, MD, PhD, dean of research and education at the Exercise Medicine Clinic at CLINIMEX in Rio de Janeiro, Brazil, told this news organization. The test can also measure progress.

“Guidelines talk about how much exercise you should do every week, but it’s somewhat misleading because the health outcomes are much more linked to physical fitness than the amount of exercise you do,” Dr. Araújo said. Treating a patient with hypertension requires an individualized approach. “The same thing is true with exercise,” he said.

A person with high aerobic fitness, either because of favorable genetics or because he or she has maintained good fitness by exercising, may need less activity, but 200 minutes per week may not be enough for someone else.

In his own lab, Dr. Araújo is following “dozens” of men and women who have been able to increase their ability to exercise – especially high-intensity activity – over time. And their VO₂ max readings have risen, he said.

Getting patients moving and collecting data on VO₂ max is the most precise way to measure aerobic fitness. But the test is far from a staple in primary care.

Dr. Araújo said a growing body of research has long shown VO₂ max to be a significant determinant of health and one that physicians should be paying closer attention to, especially for aging patients.

“If someone has a low VO₂ max, the treatment to correct this unfavorable health profile is to increase exercise levels,” Dr. Araújo said. “This is a very relevant public health message.”

Investigators have found that inactivity increases a person’s risk of dying from an atherosclerotic cardiovascular disease event by about the same amount as smoking, and that a sedentary lifestyle increases with age . A patient’s fitness is crucial to his or her overall health, and VO₂ max can play a key role. Poor performance on CPET could be a warning regarding a number of conditions, particularly cardiovascular and lung disease, Dr. Araújo said.

Indeed, acing the CPET is not easy.

“Your joints have to be normal, you can’t have low potassium, low sodium, or high blood sugar, your heart has to pump well, your blood vessels have to be healthy,” said Thomas Allison, PhD, MPH, director of the Integrated Stress Testing Center and the Sports Cardiology Clinic at Mayo Clinic, in Rochester, Minn. “All of those things can show up on the treadmill in terms of your VO₂ max.”

Low VO₂ max can be a physician’s first indication to investigate further. A review published in November 2022 in the International Journal of Cardiology Cardiovascular Risk and Prevention outlined what cross-sectional and longitudinal studies have documented regarding how VO₂ max changes as people age. From ages 18 to 35, VO₂ max remains fairly consistent. Between 35 and 55, it drops slightly but inexorably before falling sharply, if inconsistently. This inconsistency is where the important data lie.

“That lower level of physical activity may just be a behavioral change that needs to be reversed, or it could be a change that has been forced by underlying occult disease,” Dr. Allison said. That older people can’t run as fast as young people or are more likely to die in a given period than young people is not surprising. “The question is, at any given age, does your fitness level predict good health outcomes?” he said. “And the answer is yes.”

Fitness should be treated as any other data point, he added.

“If I want to know your blood pressure, I’m going to check your blood pressure; I’m not going to just ask you what it is,” Dr. Allison said. “If I ask if you have any limitations or symptoms with exercise or how physically active you are, if possible, I want to check that.”
 

Culture shift

Dr. Forman acknowledged that VO₂ max tests can be difficult and expensive to administer in offices that aren’t already equipped with CPET machines. He said conducting other assessments, such as observing the patient performing a short walk, won’t provide as accurate data but is better than not assessing function at all.

“Specialists all have different things they measure, but function is the common denominator. For an aging population, it is the number one thing we should be looking at,” Dr. Forman said. “It’s a skill set, it’s an investment, it’s a change in culture at a time when cardiologists are obsessed with getting the latest imaging machines.”

Dr. Allison said all cardiologists should assess their patients’ VO₂ max and that family medicine doctors should use the test for certain patients, such as those who have gained an unusual amount of weight or report being out of breath more than usual.

“We have all sorts of things that can go wrong with us as we get older, but if we’re sitting in a doctor’s office, it may not be apparent what they are,” Dr. Allison said. “We have to get patients up and moving.”

The authors have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Physicians routinely monitor cholesterol, blood pressure, and glucose levels to get a clearer picture of their patients’ overall health. But a group of experts argues that having an accurate read of a person’s ability to absorb oxygen during peak exertion – VO₂ max – is just as important.

Once the focus of cyclists and other elite athletes, VO₂ max has in recent years caught the attention of geriatricians, who have linked the measure to maximum functional capacity – an umbrella term for the body’s ability to perform aerobic exercise.

“Function is prognostic of mortality,” said Daniel E. Forman, MD, FAHA, FACC, professor of medicine and chair of the section of geriatric cardiology at the University of Pittsburgh Medical Center. “If you aren’t looking at that, you’re missing the boat.”

Although cardiopulmonary exercise testing (CPET) remains the gold standard for assessing VO₂ max, Dr. Forman said clinicians often overlook CPET because it is old.
 

Getting precise

As a person ages, the amount of physical activity needed to stay fit varies, depending on genes, health, and fitness history. Measuring VO₂ max can help doctors better prescribe physical activity, both with regard to specific exercises and for how long, Claudio Gil Araújo, MD, PhD, dean of research and education at the Exercise Medicine Clinic at CLINIMEX in Rio de Janeiro, Brazil, told this news organization. The test can also measure progress.

“Guidelines talk about how much exercise you should do every week, but it’s somewhat misleading because the health outcomes are much more linked to physical fitness than the amount of exercise you do,” Dr. Araújo said. Treating a patient with hypertension requires an individualized approach. “The same thing is true with exercise,” he said.

A person with high aerobic fitness, either because of favorable genetics or because he or she has maintained good fitness by exercising, may need less activity, but 200 minutes per week may not be enough for someone else.

In his own lab, Dr. Araújo is following “dozens” of men and women who have been able to increase their ability to exercise – especially high-intensity activity – over time. And their VO₂ max readings have risen, he said.

Getting patients moving and collecting data on VO₂ max is the most precise way to measure aerobic fitness. But the test is far from a staple in primary care.

Dr. Araújo said a growing body of research has long shown VO₂ max to be a significant determinant of health and one that physicians should be paying closer attention to, especially for aging patients.

“If someone has a low VO₂ max, the treatment to correct this unfavorable health profile is to increase exercise levels,” Dr. Araújo said. “This is a very relevant public health message.”

Investigators have found that inactivity increases a person’s risk of dying from an atherosclerotic cardiovascular disease event by about the same amount as smoking, and that a sedentary lifestyle increases with age . A patient’s fitness is crucial to his or her overall health, and VO₂ max can play a key role. Poor performance on CPET could be a warning regarding a number of conditions, particularly cardiovascular and lung disease, Dr. Araújo said.

Indeed, acing the CPET is not easy.

“Your joints have to be normal, you can’t have low potassium, low sodium, or high blood sugar, your heart has to pump well, your blood vessels have to be healthy,” said Thomas Allison, PhD, MPH, director of the Integrated Stress Testing Center and the Sports Cardiology Clinic at Mayo Clinic, in Rochester, Minn. “All of those things can show up on the treadmill in terms of your VO₂ max.”

Low VO₂ max can be a physician’s first indication to investigate further. A review published in November 2022 in the International Journal of Cardiology Cardiovascular Risk and Prevention outlined what cross-sectional and longitudinal studies have documented regarding how VO₂ max changes as people age. From ages 18 to 35, VO₂ max remains fairly consistent. Between 35 and 55, it drops slightly but inexorably before falling sharply, if inconsistently. This inconsistency is where the important data lie.

“That lower level of physical activity may just be a behavioral change that needs to be reversed, or it could be a change that has been forced by underlying occult disease,” Dr. Allison said. That older people can’t run as fast as young people or are more likely to die in a given period than young people is not surprising. “The question is, at any given age, does your fitness level predict good health outcomes?” he said. “And the answer is yes.”

Fitness should be treated as any other data point, he added.

“If I want to know your blood pressure, I’m going to check your blood pressure; I’m not going to just ask you what it is,” Dr. Allison said. “If I ask if you have any limitations or symptoms with exercise or how physically active you are, if possible, I want to check that.”
 

Culture shift

Dr. Forman acknowledged that VO₂ max tests can be difficult and expensive to administer in offices that aren’t already equipped with CPET machines. He said conducting other assessments, such as observing the patient performing a short walk, won’t provide as accurate data but is better than not assessing function at all.

“Specialists all have different things they measure, but function is the common denominator. For an aging population, it is the number one thing we should be looking at,” Dr. Forman said. “It’s a skill set, it’s an investment, it’s a change in culture at a time when cardiologists are obsessed with getting the latest imaging machines.”

Dr. Allison said all cardiologists should assess their patients’ VO₂ max and that family medicine doctors should use the test for certain patients, such as those who have gained an unusual amount of weight or report being out of breath more than usual.

“We have all sorts of things that can go wrong with us as we get older, but if we’re sitting in a doctor’s office, it may not be apparent what they are,” Dr. Allison said. “We have to get patients up and moving.”

The authors have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Physicians routinely monitor cholesterol, blood pressure, and glucose levels to get a clearer picture of their patients’ overall health. But a group of experts argues that having an accurate read of a person’s ability to absorb oxygen during peak exertion – VO₂ max – is just as important.

Once the focus of cyclists and other elite athletes, VO₂ max has in recent years caught the attention of geriatricians, who have linked the measure to maximum functional capacity – an umbrella term for the body’s ability to perform aerobic exercise.

“Function is prognostic of mortality,” said Daniel E. Forman, MD, FAHA, FACC, professor of medicine and chair of the section of geriatric cardiology at the University of Pittsburgh Medical Center. “If you aren’t looking at that, you’re missing the boat.”

Although cardiopulmonary exercise testing (CPET) remains the gold standard for assessing VO₂ max, Dr. Forman said clinicians often overlook CPET because it is old.
 

Getting precise

As a person ages, the amount of physical activity needed to stay fit varies, depending on genes, health, and fitness history. Measuring VO₂ max can help doctors better prescribe physical activity, both with regard to specific exercises and for how long, Claudio Gil Araújo, MD, PhD, dean of research and education at the Exercise Medicine Clinic at CLINIMEX in Rio de Janeiro, Brazil, told this news organization. The test can also measure progress.

“Guidelines talk about how much exercise you should do every week, but it’s somewhat misleading because the health outcomes are much more linked to physical fitness than the amount of exercise you do,” Dr. Araújo said. Treating a patient with hypertension requires an individualized approach. “The same thing is true with exercise,” he said.

A person with high aerobic fitness, either because of favorable genetics or because he or she has maintained good fitness by exercising, may need less activity, but 200 minutes per week may not be enough for someone else.

In his own lab, Dr. Araújo is following “dozens” of men and women who have been able to increase their ability to exercise – especially high-intensity activity – over time. And their VO₂ max readings have risen, he said.

Getting patients moving and collecting data on VO₂ max is the most precise way to measure aerobic fitness. But the test is far from a staple in primary care.

Dr. Araújo said a growing body of research has long shown VO₂ max to be a significant determinant of health and one that physicians should be paying closer attention to, especially for aging patients.

“If someone has a low VO₂ max, the treatment to correct this unfavorable health profile is to increase exercise levels,” Dr. Araújo said. “This is a very relevant public health message.”

Investigators have found that inactivity increases a person’s risk of dying from an atherosclerotic cardiovascular disease event by about the same amount as smoking, and that a sedentary lifestyle increases with age . A patient’s fitness is crucial to his or her overall health, and VO₂ max can play a key role. Poor performance on CPET could be a warning regarding a number of conditions, particularly cardiovascular and lung disease, Dr. Araújo said.

Indeed, acing the CPET is not easy.

“Your joints have to be normal, you can’t have low potassium, low sodium, or high blood sugar, your heart has to pump well, your blood vessels have to be healthy,” said Thomas Allison, PhD, MPH, director of the Integrated Stress Testing Center and the Sports Cardiology Clinic at Mayo Clinic, in Rochester, Minn. “All of those things can show up on the treadmill in terms of your VO₂ max.”

Low VO₂ max can be a physician’s first indication to investigate further. A review published in November 2022 in the International Journal of Cardiology Cardiovascular Risk and Prevention outlined what cross-sectional and longitudinal studies have documented regarding how VO₂ max changes as people age. From ages 18 to 35, VO₂ max remains fairly consistent. Between 35 and 55, it drops slightly but inexorably before falling sharply, if inconsistently. This inconsistency is where the important data lie.

“That lower level of physical activity may just be a behavioral change that needs to be reversed, or it could be a change that has been forced by underlying occult disease,” Dr. Allison said. That older people can’t run as fast as young people or are more likely to die in a given period than young people is not surprising. “The question is, at any given age, does your fitness level predict good health outcomes?” he said. “And the answer is yes.”

Fitness should be treated as any other data point, he added.

“If I want to know your blood pressure, I’m going to check your blood pressure; I’m not going to just ask you what it is,” Dr. Allison said. “If I ask if you have any limitations or symptoms with exercise or how physically active you are, if possible, I want to check that.”
 

Culture shift

Dr. Forman acknowledged that VO₂ max tests can be difficult and expensive to administer in offices that aren’t already equipped with CPET machines. He said conducting other assessments, such as observing the patient performing a short walk, won’t provide as accurate data but is better than not assessing function at all.

“Specialists all have different things they measure, but function is the common denominator. For an aging population, it is the number one thing we should be looking at,” Dr. Forman said. “It’s a skill set, it’s an investment, it’s a change in culture at a time when cardiologists are obsessed with getting the latest imaging machines.”

Dr. Allison said all cardiologists should assess their patients’ VO₂ max and that family medicine doctors should use the test for certain patients, such as those who have gained an unusual amount of weight or report being out of breath more than usual.

“We have all sorts of things that can go wrong with us as we get older, but if we’re sitting in a doctor’s office, it may not be apparent what they are,” Dr. Allison said. “We have to get patients up and moving.”

The authors have disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

Butylphthalide, a medication derived from celery seed, may improve outcomes after an acute ischemic stroke when given in addition to thrombolysis or endovascular treatment, a new report suggests.

Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.

Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.

“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”

The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Studying stroke outcomes

The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.

In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.

The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.

Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.

The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).

Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.

Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.

Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).

In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.

Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
 

Ongoing questions

Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.

“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.

Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.

“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.

Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.

“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”

The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Butylphthalide, a medication derived from celery seed, may improve outcomes after an acute ischemic stroke when given in addition to thrombolysis or endovascular treatment, a new report suggests.

Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.

Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.

“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”

The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Studying stroke outcomes

The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.

In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.

The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.

Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.

The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).

Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.

Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.

Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).

In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.

Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
 

Ongoing questions

Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.

“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.

Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.

“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.

Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.

“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”

The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Butylphthalide, a medication derived from celery seed, may improve outcomes after an acute ischemic stroke when given in addition to thrombolysis or endovascular treatment, a new report suggests.

Patients treated with butylphthalide had fewer severe neurologic symptoms and better function 90 days after the stroke, compared with those receiving placebo.

Butylphthalide is approved and available for use in China, where the study was conducted. However, the medication hasn’t been approved for use by the U.S. Food and Drug Administration.

“Patients who received butylphthalide had less severe neurological symptoms and a better living status at 90 days post stroke, compared to those who received the placebo,” said coauthor Baixue Jia, MD, an attending physician in interventional neuroradiology at the Beijing Tiantan Hospital of Capital Medical University and a faculty member at the China National Clinical Research Center for Neurological Diseases in Beijing. “If the results are confirmed in other trials, this may lead to more options to treat strokes caused by clots.”

The study was presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.
 

Studying stroke outcomes

The researchers described butylphthalide as a cerebroprotective drug that was originally extracted from seeds of Apium graveolens. In China, previous studies have shown that the drug has cerebroprotective effects in animal models of ischemia-reperfusion, they noted.

In this randomized, double-blind, placebo-controlled trial, Dr. Jia and colleagues evaluated whether treatment with butylphthalide could improve 90-day outcomes for adults with acute ischemic stroke who received intravenous recombinant tissue plasminogen activator (tPA), endovascular treatment, or both.

The participants were treated at one of 59 medical centers in China between July 2018 and February 2022. Those who had minimal stroke symptoms on their initial exam, defined as a score of 0-3 on the National Institutes of Health Stroke Scale, or had severe stroke symptoms, defined as having a score of 26 or higher on the NIHSS, were excluded from the study.

Along with an initial revascularization intervention chosen by their physician, participants were randomly selected to receive either butylphthalide or a placebo daily for 90 days. The drug was administered through daily intravenous injections for the first 14 days, after which patients received oral capsules for 76 days.

The research team defined the outcomes as “favorable” if a patient fell into one of the following categories 90 days after the stroke: an initially mild to moderate stroke (NIHSS, 4-7) and no symptoms after treatment, defined as a score of 0 on the Modified Rankin Scale (mRS), which measures disability and dependence; an initially moderate to serious stroke (NIHSS, 8-14) and no residual symptoms or mild symptoms that don’t impair the ability to perform routine activities of daily living without assistance (mRS, 0-1); or an initially serious to severe stroke (NIHSS, 15-25) and no remaining symptoms or a slight disability that impairs some activities but allows one to conduct daily living without assistance (mRS, 0-2).

Secondary outcomes included symptomatic intracranial hemorrhage, recurrent stroke, and mortality.

Among the 1,216 participants, 607 were assigned to the treatment group, and 609 were assigned to the placebo group. The average age was 66 years, and 68% were men.

Overall, participants in the butylphthalide group were 70% more likely to have a favorable 90-day outcome, compared with the placebo group. Favorable outcomes occurred in 344 patients (56.7%) in the butylphthalide group, compared with 268 patients (44%) in the placebo group (odds ratio, 1.70; 95% confidence interval, 1.35-2.14; P < .001).

In addition, butylphthalide improved function equally well for the patients who initially received tPA, those who received endovascular treatment, and those who received both tPA and endovascular treatment.

Secondary events, such as recurrent stroke and intracranial hemorrhage, weren’t significantly different between the butylphthalide and placebo groups.
 

Ongoing questions

Dr. Jia and colleagues noted the need to understand how butylphthalide works in the brain. Animal studies have suggested several possible mechanisms, but it remains unclear.

“The next step should be investigating the exact mechanisms of butylphthalide in humans,” Dr. Jia said.

Additional research should assess the medication in other populations, the authors noted, particularly because the study involved participants who received initial treatment with tPA, endovascular treatment, or both. The results may not be generalizable to stroke patients who receive other treatments or to populations outside of China.

“While these are interesting results, this is only one relatively small study on a fairly select population in China. Butylphthalide, a medication initially compounded from celery seed, is not ready for use in standard stroke treatment,” said Daniel Lackland, DrPH, professor of neurology and director of the division of translational neurosciences and population studies at the Medical University of South Carolina, Charleston.

Dr. Lackland, who wasn’t involved with the study, is a member of the American Stroke Association’s Stroke Council. Although butylphthalide was originally extracted from seeds, he noted, it’s not what patients would find commercially available.

“The medication used in this study is not the same as celery seed or celery seed extract supplements,” he said. “Stroke survivors should always consult with their neurologist or healthcare professional regarding diet after a stroke.”

The study was funded by the National Key Technology Research and Development Program of the Ministry of Science and Technology of the People’s Republic of China and Shijiazhuang Pharmaceutical Group dl-3-butylphthalide Pharmaceutical. Several authors are employed with Beijing Tiantan Hospital and the Beijing Institute of Brain Disorders. Dr. Lackland reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.