Cardiology News

Nearly 60% of Medicaid-covered adults with concurrent diabetes and heart failure did not receive guideline-concordant postdischarge care within 7-10 days of leaving the hospital, according to a large Alabama study. Moreover, affected Black and Hispanic/other Alabamians were less likely than were their White counterparts to receive recommended postdischarge care.

In comparison with White participants, Black and Hispanic adults were less likely to have any postdischarge ambulatory care visits after HF hospitalization or had a delayed visit, according to researchers led by Yulia Khodneva, MD, PhD, an internist at the University of Alabama at Birmingham. “This is likely a reflection of a structural racism and implicit bias against racial and ethnic minorities that persists in the U.S. health care system,” she and her colleagues wrote.

The findings point to the need for strategies to improve access to postdischarge care for lower-income HF patients.

Among U.S. states, Alabama is the sixth-poorest, the third in diabetes prevalence (14%), and has the highest rates of heart failure hospitalizations and cardiovascular mortality, the authors noted.

Study details

The cohort included 9,857 adults with diabetes and first hospitalizations for heart failure who were covered by Alabama Medicaid during 2010-2019. The investigators analyzed patients’ claims for ambulatory care (any, primary, cardiology, or endocrinology) within 60 days of discharge.

The mean age of participants was 53.7 years; 47.3% were Black; 41.8% non-Hispanic White; and 10.9% Hispanic/other, with other including those identifying as non-White Hispanic, American Indian, Pacific Islander, and Asian. About two-thirds (65.4%) of participants were women.

Analysis revealed low rates of follow-up care after hospital discharge; 26.7% had an ambulatory visit within 0-7 days, 15.2% within 8-14 days, 31.3% within 15-60 days, and 26.8% had no follow-up visit at all. Of those having a follow-up visit, 71% saw a primary care physician and 12% saw a cardiologist.

In contrast, a much higher proportion of heart failure patients in a Swedish registry – 63% – received ambulatory follow-up in cardiology.
 

Ethnic/gender/age disparities

Black and Hispanic/other adults were less likely to have any postdischarge ambulatory visit (P <.0001) or had the visit delayed by 1.8 days (P = .0006) and 2.8 days (P = .0016), respectively. They were less likely to see a primary care physician than were non-Hispanic White adults: adjusted incidence rate ratio, 0.96 (95% confidence interval [CI], 0.91-1.00) and 0.91 (95% CI, 0.89-0.98), respectively.

Men and those with longer-standing heart failure were less likely to be seen in primary care, while the presence of multiple comorbidities was associated with a higher likelihood of a postdischarge primary care visit. Men were more likely to be seen by a cardiologist, while older discharged patients were less likely to be seen by an endocrinologist within 60 days. There was a U-shaped relationship between the timing of the first postdischarge ambulatory visit and all-cause mortality among adults with diabetes and heart failure. Higher rates of 60-day all-cause mortality were observed both in those who had seen a provider within 0-7 days after discharge and in those who had not seen any provider during the 60-day study period compared with those having an ambulatory care visit within 7-14 or 15-60 days. “The group with early follow-up (0-7 days) likely represents a sicker population of patients with heart failure with more comorbidity burden and higher overall health care use, including readmissions, as was demonstrated in our analysis,” Dr. Khodneva and associates wrote. “Interventions that improve access to postdischarge ambulatory care for low-income patients with diabetes and heart failure and eliminate racial and ethnic disparities may be warranted,” they added.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of Alabama at Birmingham Diabetes Research Center. Dr. Khodneva reported funding from the University of Alabama at Birmingham and the Forge Ahead Center as well as from the NIDDK, the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Alabama Medicaid Agency. Coauthor Emily Levitan, ScD, reported research funding from Amgen and has served on Amgen advisory boards. She has also served as a scientific consultant for a research project funded by Novartis.

Nearly 60% of Medicaid-covered adults with concurrent diabetes and heart failure did not receive guideline-concordant postdischarge care within 7-10 days of leaving the hospital, according to a large Alabama study. Moreover, affected Black and Hispanic/other Alabamians were less likely than were their White counterparts to receive recommended postdischarge care.

In comparison with White participants, Black and Hispanic adults were less likely to have any postdischarge ambulatory care visits after HF hospitalization or had a delayed visit, according to researchers led by Yulia Khodneva, MD, PhD, an internist at the University of Alabama at Birmingham. “This is likely a reflection of a structural racism and implicit bias against racial and ethnic minorities that persists in the U.S. health care system,” she and her colleagues wrote.

The findings point to the need for strategies to improve access to postdischarge care for lower-income HF patients.

Among U.S. states, Alabama is the sixth-poorest, the third in diabetes prevalence (14%), and has the highest rates of heart failure hospitalizations and cardiovascular mortality, the authors noted.

Study details

The cohort included 9,857 adults with diabetes and first hospitalizations for heart failure who were covered by Alabama Medicaid during 2010-2019. The investigators analyzed patients’ claims for ambulatory care (any, primary, cardiology, or endocrinology) within 60 days of discharge.

The mean age of participants was 53.7 years; 47.3% were Black; 41.8% non-Hispanic White; and 10.9% Hispanic/other, with other including those identifying as non-White Hispanic, American Indian, Pacific Islander, and Asian. About two-thirds (65.4%) of participants were women.

Analysis revealed low rates of follow-up care after hospital discharge; 26.7% had an ambulatory visit within 0-7 days, 15.2% within 8-14 days, 31.3% within 15-60 days, and 26.8% had no follow-up visit at all. Of those having a follow-up visit, 71% saw a primary care physician and 12% saw a cardiologist.

In contrast, a much higher proportion of heart failure patients in a Swedish registry – 63% – received ambulatory follow-up in cardiology.
 

Ethnic/gender/age disparities

Black and Hispanic/other adults were less likely to have any postdischarge ambulatory visit (P <.0001) or had the visit delayed by 1.8 days (P = .0006) and 2.8 days (P = .0016), respectively. They were less likely to see a primary care physician than were non-Hispanic White adults: adjusted incidence rate ratio, 0.96 (95% confidence interval [CI], 0.91-1.00) and 0.91 (95% CI, 0.89-0.98), respectively.

Men and those with longer-standing heart failure were less likely to be seen in primary care, while the presence of multiple comorbidities was associated with a higher likelihood of a postdischarge primary care visit. Men were more likely to be seen by a cardiologist, while older discharged patients were less likely to be seen by an endocrinologist within 60 days. There was a U-shaped relationship between the timing of the first postdischarge ambulatory visit and all-cause mortality among adults with diabetes and heart failure. Higher rates of 60-day all-cause mortality were observed both in those who had seen a provider within 0-7 days after discharge and in those who had not seen any provider during the 60-day study period compared with those having an ambulatory care visit within 7-14 or 15-60 days. “The group with early follow-up (0-7 days) likely represents a sicker population of patients with heart failure with more comorbidity burden and higher overall health care use, including readmissions, as was demonstrated in our analysis,” Dr. Khodneva and associates wrote. “Interventions that improve access to postdischarge ambulatory care for low-income patients with diabetes and heart failure and eliminate racial and ethnic disparities may be warranted,” they added.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of Alabama at Birmingham Diabetes Research Center. Dr. Khodneva reported funding from the University of Alabama at Birmingham and the Forge Ahead Center as well as from the NIDDK, the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Alabama Medicaid Agency. Coauthor Emily Levitan, ScD, reported research funding from Amgen and has served on Amgen advisory boards. She has also served as a scientific consultant for a research project funded by Novartis.

Nearly 60% of Medicaid-covered adults with concurrent diabetes and heart failure did not receive guideline-concordant postdischarge care within 7-10 days of leaving the hospital, according to a large Alabama study. Moreover, affected Black and Hispanic/other Alabamians were less likely than were their White counterparts to receive recommended postdischarge care.

In comparison with White participants, Black and Hispanic adults were less likely to have any postdischarge ambulatory care visits after HF hospitalization or had a delayed visit, according to researchers led by Yulia Khodneva, MD, PhD, an internist at the University of Alabama at Birmingham. “This is likely a reflection of a structural racism and implicit bias against racial and ethnic minorities that persists in the U.S. health care system,” she and her colleagues wrote.

The findings point to the need for strategies to improve access to postdischarge care for lower-income HF patients.

Among U.S. states, Alabama is the sixth-poorest, the third in diabetes prevalence (14%), and has the highest rates of heart failure hospitalizations and cardiovascular mortality, the authors noted.

Study details

The cohort included 9,857 adults with diabetes and first hospitalizations for heart failure who were covered by Alabama Medicaid during 2010-2019. The investigators analyzed patients’ claims for ambulatory care (any, primary, cardiology, or endocrinology) within 60 days of discharge.

The mean age of participants was 53.7 years; 47.3% were Black; 41.8% non-Hispanic White; and 10.9% Hispanic/other, with other including those identifying as non-White Hispanic, American Indian, Pacific Islander, and Asian. About two-thirds (65.4%) of participants were women.

Analysis revealed low rates of follow-up care after hospital discharge; 26.7% had an ambulatory visit within 0-7 days, 15.2% within 8-14 days, 31.3% within 15-60 days, and 26.8% had no follow-up visit at all. Of those having a follow-up visit, 71% saw a primary care physician and 12% saw a cardiologist.

In contrast, a much higher proportion of heart failure patients in a Swedish registry – 63% – received ambulatory follow-up in cardiology.
 

Ethnic/gender/age disparities

Black and Hispanic/other adults were less likely to have any postdischarge ambulatory visit (P <.0001) or had the visit delayed by 1.8 days (P = .0006) and 2.8 days (P = .0016), respectively. They were less likely to see a primary care physician than were non-Hispanic White adults: adjusted incidence rate ratio, 0.96 (95% confidence interval [CI], 0.91-1.00) and 0.91 (95% CI, 0.89-0.98), respectively.

Men and those with longer-standing heart failure were less likely to be seen in primary care, while the presence of multiple comorbidities was associated with a higher likelihood of a postdischarge primary care visit. Men were more likely to be seen by a cardiologist, while older discharged patients were less likely to be seen by an endocrinologist within 60 days. There was a U-shaped relationship between the timing of the first postdischarge ambulatory visit and all-cause mortality among adults with diabetes and heart failure. Higher rates of 60-day all-cause mortality were observed both in those who had seen a provider within 0-7 days after discharge and in those who had not seen any provider during the 60-day study period compared with those having an ambulatory care visit within 7-14 or 15-60 days. “The group with early follow-up (0-7 days) likely represents a sicker population of patients with heart failure with more comorbidity burden and higher overall health care use, including readmissions, as was demonstrated in our analysis,” Dr. Khodneva and associates wrote. “Interventions that improve access to postdischarge ambulatory care for low-income patients with diabetes and heart failure and eliminate racial and ethnic disparities may be warranted,” they added.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the University of Alabama at Birmingham Diabetes Research Center. Dr. Khodneva reported funding from the University of Alabama at Birmingham and the Forge Ahead Center as well as from the NIDDK, the National Institutes of Health, the Agency for Healthcare Research and Quality, and the Alabama Medicaid Agency. Coauthor Emily Levitan, ScD, reported research funding from Amgen and has served on Amgen advisory boards. She has also served as a scientific consultant for a research project funded by Novartis.

Abiomed has recalled 466 of its Impella 5.5 with SmartAssist heart pumps after receiving customer complaints about purge fluid leaking from the purge sidearm of the pump.

“If a purge leak occurs, the system will experience low purge pressures, prompting alarms and requiring evaluation,” the U.S. Food and Drug Administration says in an advisory posted on its website.

A version of this article was first published on Medscape.com.

Abiomed has recalled 466 of its Impella 5.5 with SmartAssist heart pumps after receiving customer complaints about purge fluid leaking from the purge sidearm of the pump.

“If a purge leak occurs, the system will experience low purge pressures, prompting alarms and requiring evaluation,” the U.S. Food and Drug Administration says in an advisory posted on its website.

A version of this article was first published on Medscape.com.

Abiomed has recalled 466 of its Impella 5.5 with SmartAssist heart pumps after receiving customer complaints about purge fluid leaking from the purge sidearm of the pump.

“If a purge leak occurs, the system will experience low purge pressures, prompting alarms and requiring evaluation,” the U.S. Food and Drug Administration says in an advisory posted on its website.

A version of this article was first published on Medscape.com.

A system of personalized alerts via an electronic health record (EHR) network failed to boost discharge prescriptions for guideline-directed medical therapy (GDMT) for patients hospitalized with heart failure (HF) with reduced ejection fraction in a randomized trial conducted at several centers in the same health care system.

The results of the PROMPT-AHF trial, which assigned such patients to have or not have the GDMT-promoting physician nudges as part of their in-hospital management, were “not entirely surprising,” Tariq Ahmad, MD, MPH, of Yale University, New Haven, Conn., said in an interview.

“We have created an environment in the hospital that makes care quite fractured for patients with heart failure,” he said. “They are cared for by many different clinicians, which leads to well-known behaviors such as diffusion of responsibility.”

Moreover, many clinicians focus on stabilizing patients “rather than starting them on a comprehensive set of medications, which most think should be done after discharge,” Dr. Ahmad added.

“Importantly, there has been a logarithmic increase in alerts while patients are hospitalized that has caused clinician burnout and is leading to even very important alerts being ignored.”

Likely as a result, the trial saw no significant difference between the alert and no-alert groups in how often the number of GDMT prescriptions rose by at least one drug class, whether beta blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, or SGLT2 inhibitors. That happened for 34% of patients in both groups, reported Dr. Ahmad at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions

Nor was there a difference in the secondary endpoint of increased number of GDMT meds or escalated dosage of prescribed GDMT drugs.
 

GDMT ‘uncommon’ in AHF

In an earlier trial in outpatients with chronic HF, conducted by many of the same researchers, use of a targeted EHR-based alert system was associated with significantly higher rates of GDMT prescriptions 30 days after discharge, compared with usual care, Dr. Ahmad observed in his presentation.

Because GDMT is similarly “uncommon” among patients hospitalized with acute HF, the team designed the current trial, a test of the hypothesis that a similar system of nudges would lead to higher rates of prescriptions of the four core GDMT drug classes.

The study enrolled 920 adults with acute HF, an EF of 40% or lower (their median was 28%), and NT-proBNP levels higher than 500 pg/mL. The patients received IV diuretics for the first 24 in-hospital hours and were not taking medications from any of the four core HF drug classes. Their mean age was 74, 36% were women, and 25% were Black.

Physicians of patients who were randomly assigned to the intervention received the alerts as they entered information that involved ejection fraction, blood pressure, potassium levels, heart rate, glomerular filtration rate, and meds they were currently or should be taking, “along with an order set that made ordering those medications very easy,” Dr. Ahmad said.

“There was absolutely no evidence that the alert made any difference. There were zero patients on all four classes of GDMT at baseline, and at the time of discharge, only 11.2% of patients were on all four pillars – essentially, one in nine patients,” Dr. Ahmad said. Nor were there any subgroup differences in age, sex, race, ejection fraction, type of health insurance, or whether care was provided by a cardiologist or noncardiologist physician.

The study was limited by having been conducted within a single health care network using only the Epic EHR system. The alerts did not go exclusively to cardiologists, and patient preferences were not considered in the analysis. Also, the study’s alerts represented only some of the many that were received by the clinicians during the course of the trial.
 

Better incentives needed

“We believe this shows that refinement of the nudges is needed, as well as changes to clinician incentives to overcome barriers to implementation of GDMT during hospitalizations for AHF,” Dr. Ahmad said.

Responding to a postpresentation question on whether the postdischarge phase might be a more effective time to intervene with nudges, Dr. Ahmad observed that many clinicians who care for patients in the hospital assume that someone else will have the patient receive appropriate meds after discharge. “But we know that things that are started in the hospital tend to stick better.

“I do think that a lot of the clinicians were thinking, ‘I’m just going to get this patient out and someone in the outside will get them on GDMT,’ ” he said.

In the United States there are many incentives to reduce hospital length of stay and to expedite discharge so more beds are available for incoming patients, Dr. Ahmad observed. “I think it’s a combination of these kinds of perverse incentives that are not allowing us to get patients on appropriate GDMT during hospitalization.”

Furthermore, Dr. Ahmad told this news organization, “additions to the EHR should be evaluated in an evidence-based manner. However, the opposite has occurred, with an unregulated data tsunami crushing clinicians, which has been bad both for the clinicians and for patients.”

The study was funded by AstraZeneca. Dr. Ahmad discloses receiving research funding from and consulting for AstraZeneca; and receiving research funding from Boehringer Ingelheim, Cytokinetics, and Relypsa. Three other coauthors are employees of AstraZeneca.

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

A system of personalized alerts via an electronic health record (EHR) network failed to boost discharge prescriptions for guideline-directed medical therapy (GDMT) for patients hospitalized with heart failure (HF) with reduced ejection fraction in a randomized trial conducted at several centers in the same health care system.

The results of the PROMPT-AHF trial, which assigned such patients to have or not have the GDMT-promoting physician nudges as part of their in-hospital management, were “not entirely surprising,” Tariq Ahmad, MD, MPH, of Yale University, New Haven, Conn., said in an interview.

“We have created an environment in the hospital that makes care quite fractured for patients with heart failure,” he said. “They are cared for by many different clinicians, which leads to well-known behaviors such as diffusion of responsibility.”

Moreover, many clinicians focus on stabilizing patients “rather than starting them on a comprehensive set of medications, which most think should be done after discharge,” Dr. Ahmad added.

“Importantly, there has been a logarithmic increase in alerts while patients are hospitalized that has caused clinician burnout and is leading to even very important alerts being ignored.”

Likely as a result, the trial saw no significant difference between the alert and no-alert groups in how often the number of GDMT prescriptions rose by at least one drug class, whether beta blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, or SGLT2 inhibitors. That happened for 34% of patients in both groups, reported Dr. Ahmad at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions

Nor was there a difference in the secondary endpoint of increased number of GDMT meds or escalated dosage of prescribed GDMT drugs.
 

GDMT ‘uncommon’ in AHF

In an earlier trial in outpatients with chronic HF, conducted by many of the same researchers, use of a targeted EHR-based alert system was associated with significantly higher rates of GDMT prescriptions 30 days after discharge, compared with usual care, Dr. Ahmad observed in his presentation.

Because GDMT is similarly “uncommon” among patients hospitalized with acute HF, the team designed the current trial, a test of the hypothesis that a similar system of nudges would lead to higher rates of prescriptions of the four core GDMT drug classes.

The study enrolled 920 adults with acute HF, an EF of 40% or lower (their median was 28%), and NT-proBNP levels higher than 500 pg/mL. The patients received IV diuretics for the first 24 in-hospital hours and were not taking medications from any of the four core HF drug classes. Their mean age was 74, 36% were women, and 25% were Black.

Physicians of patients who were randomly assigned to the intervention received the alerts as they entered information that involved ejection fraction, blood pressure, potassium levels, heart rate, glomerular filtration rate, and meds they were currently or should be taking, “along with an order set that made ordering those medications very easy,” Dr. Ahmad said.

“There was absolutely no evidence that the alert made any difference. There were zero patients on all four classes of GDMT at baseline, and at the time of discharge, only 11.2% of patients were on all four pillars – essentially, one in nine patients,” Dr. Ahmad said. Nor were there any subgroup differences in age, sex, race, ejection fraction, type of health insurance, or whether care was provided by a cardiologist or noncardiologist physician.

The study was limited by having been conducted within a single health care network using only the Epic EHR system. The alerts did not go exclusively to cardiologists, and patient preferences were not considered in the analysis. Also, the study’s alerts represented only some of the many that were received by the clinicians during the course of the trial.
 

Better incentives needed

“We believe this shows that refinement of the nudges is needed, as well as changes to clinician incentives to overcome barriers to implementation of GDMT during hospitalizations for AHF,” Dr. Ahmad said.

Responding to a postpresentation question on whether the postdischarge phase might be a more effective time to intervene with nudges, Dr. Ahmad observed that many clinicians who care for patients in the hospital assume that someone else will have the patient receive appropriate meds after discharge. “But we know that things that are started in the hospital tend to stick better.

“I do think that a lot of the clinicians were thinking, ‘I’m just going to get this patient out and someone in the outside will get them on GDMT,’ ” he said.

In the United States there are many incentives to reduce hospital length of stay and to expedite discharge so more beds are available for incoming patients, Dr. Ahmad observed. “I think it’s a combination of these kinds of perverse incentives that are not allowing us to get patients on appropriate GDMT during hospitalization.”

Furthermore, Dr. Ahmad told this news organization, “additions to the EHR should be evaluated in an evidence-based manner. However, the opposite has occurred, with an unregulated data tsunami crushing clinicians, which has been bad both for the clinicians and for patients.”

The study was funded by AstraZeneca. Dr. Ahmad discloses receiving research funding from and consulting for AstraZeneca; and receiving research funding from Boehringer Ingelheim, Cytokinetics, and Relypsa. Three other coauthors are employees of AstraZeneca.

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

A system of personalized alerts via an electronic health record (EHR) network failed to boost discharge prescriptions for guideline-directed medical therapy (GDMT) for patients hospitalized with heart failure (HF) with reduced ejection fraction in a randomized trial conducted at several centers in the same health care system.

The results of the PROMPT-AHF trial, which assigned such patients to have or not have the GDMT-promoting physician nudges as part of their in-hospital management, were “not entirely surprising,” Tariq Ahmad, MD, MPH, of Yale University, New Haven, Conn., said in an interview.

“We have created an environment in the hospital that makes care quite fractured for patients with heart failure,” he said. “They are cared for by many different clinicians, which leads to well-known behaviors such as diffusion of responsibility.”

Moreover, many clinicians focus on stabilizing patients “rather than starting them on a comprehensive set of medications, which most think should be done after discharge,” Dr. Ahmad added.

“Importantly, there has been a logarithmic increase in alerts while patients are hospitalized that has caused clinician burnout and is leading to even very important alerts being ignored.”

Likely as a result, the trial saw no significant difference between the alert and no-alert groups in how often the number of GDMT prescriptions rose by at least one drug class, whether beta blockers, renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, or SGLT2 inhibitors. That happened for 34% of patients in both groups, reported Dr. Ahmad at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2023 sessions

Nor was there a difference in the secondary endpoint of increased number of GDMT meds or escalated dosage of prescribed GDMT drugs.
 

GDMT ‘uncommon’ in AHF

In an earlier trial in outpatients with chronic HF, conducted by many of the same researchers, use of a targeted EHR-based alert system was associated with significantly higher rates of GDMT prescriptions 30 days after discharge, compared with usual care, Dr. Ahmad observed in his presentation.

Because GDMT is similarly “uncommon” among patients hospitalized with acute HF, the team designed the current trial, a test of the hypothesis that a similar system of nudges would lead to higher rates of prescriptions of the four core GDMT drug classes.

The study enrolled 920 adults with acute HF, an EF of 40% or lower (their median was 28%), and NT-proBNP levels higher than 500 pg/mL. The patients received IV diuretics for the first 24 in-hospital hours and were not taking medications from any of the four core HF drug classes. Their mean age was 74, 36% were women, and 25% were Black.

Physicians of patients who were randomly assigned to the intervention received the alerts as they entered information that involved ejection fraction, blood pressure, potassium levels, heart rate, glomerular filtration rate, and meds they were currently or should be taking, “along with an order set that made ordering those medications very easy,” Dr. Ahmad said.

“There was absolutely no evidence that the alert made any difference. There were zero patients on all four classes of GDMT at baseline, and at the time of discharge, only 11.2% of patients were on all four pillars – essentially, one in nine patients,” Dr. Ahmad said. Nor were there any subgroup differences in age, sex, race, ejection fraction, type of health insurance, or whether care was provided by a cardiologist or noncardiologist physician.

The study was limited by having been conducted within a single health care network using only the Epic EHR system. The alerts did not go exclusively to cardiologists, and patient preferences were not considered in the analysis. Also, the study’s alerts represented only some of the many that were received by the clinicians during the course of the trial.
 

Better incentives needed

“We believe this shows that refinement of the nudges is needed, as well as changes to clinician incentives to overcome barriers to implementation of GDMT during hospitalizations for AHF,” Dr. Ahmad said.

Responding to a postpresentation question on whether the postdischarge phase might be a more effective time to intervene with nudges, Dr. Ahmad observed that many clinicians who care for patients in the hospital assume that someone else will have the patient receive appropriate meds after discharge. “But we know that things that are started in the hospital tend to stick better.

“I do think that a lot of the clinicians were thinking, ‘I’m just going to get this patient out and someone in the outside will get them on GDMT,’ ” he said.

In the United States there are many incentives to reduce hospital length of stay and to expedite discharge so more beds are available for incoming patients, Dr. Ahmad observed. “I think it’s a combination of these kinds of perverse incentives that are not allowing us to get patients on appropriate GDMT during hospitalization.”

Furthermore, Dr. Ahmad told this news organization, “additions to the EHR should be evaluated in an evidence-based manner. However, the opposite has occurred, with an unregulated data tsunami crushing clinicians, which has been bad both for the clinicians and for patients.”

The study was funded by AstraZeneca. Dr. Ahmad discloses receiving research funding from and consulting for AstraZeneca; and receiving research funding from Boehringer Ingelheim, Cytokinetics, and Relypsa. Three other coauthors are employees of AstraZeneca.

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

The Food and Drug Administration has expanded the indication for ferric carboxymaltose injection (Injectafer, Daiichi Sankyo/American Regent) to include treatment of iron deficiency in adults with New York Heart Association (NYHA) class II/III heart failure (HF).

“This new indication for Injectafer marks the first and only FDA approval of an intravenous iron replacement therapy for adult patients with heart failure,” Ravi Tayi, MD, MPH, chief medical officer at American Regent, said in a news release.

Ferric carboxymaltose injection is also indicated for the treatment of iron deficiency anemia in adults and children as young as 1 year of age who have either intolerance or an unsatisfactory response to oral iron, and in adult patients who have nondialysis dependent chronic kidney disease.

The new indication in HF was supported by data from the CONFIRM-HF randomized controlled trial that evaluated the efficacy and safety of ferric carboxymaltose injection in adults with chronic HF and iron deficiency.

In the study, results showed that treatment with ferric carboxymaltose injection significantly improved exercise capacity compared with placebo in iron-deficient patients with HF.  

No new safety signals emerged. The most common treatment emergent adverse events were headache, nausea, hypertension, injection site reactions, hypophosphatemia, and dizziness.

According to the company, ferric carboxymaltose injection has been studied in more than 40 clinical trials that included over 8,800 patients worldwide and has been approved in 86 countries.

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

The Food and Drug Administration has expanded the indication for ferric carboxymaltose injection (Injectafer, Daiichi Sankyo/American Regent) to include treatment of iron deficiency in adults with New York Heart Association (NYHA) class II/III heart failure (HF).

“This new indication for Injectafer marks the first and only FDA approval of an intravenous iron replacement therapy for adult patients with heart failure,” Ravi Tayi, MD, MPH, chief medical officer at American Regent, said in a news release.

Ferric carboxymaltose injection is also indicated for the treatment of iron deficiency anemia in adults and children as young as 1 year of age who have either intolerance or an unsatisfactory response to oral iron, and in adult patients who have nondialysis dependent chronic kidney disease.

The new indication in HF was supported by data from the CONFIRM-HF randomized controlled trial that evaluated the efficacy and safety of ferric carboxymaltose injection in adults with chronic HF and iron deficiency.

In the study, results showed that treatment with ferric carboxymaltose injection significantly improved exercise capacity compared with placebo in iron-deficient patients with HF.  

No new safety signals emerged. The most common treatment emergent adverse events were headache, nausea, hypertension, injection site reactions, hypophosphatemia, and dizziness.

According to the company, ferric carboxymaltose injection has been studied in more than 40 clinical trials that included over 8,800 patients worldwide and has been approved in 86 countries.

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

The Food and Drug Administration has expanded the indication for ferric carboxymaltose injection (Injectafer, Daiichi Sankyo/American Regent) to include treatment of iron deficiency in adults with New York Heart Association (NYHA) class II/III heart failure (HF).

“This new indication for Injectafer marks the first and only FDA approval of an intravenous iron replacement therapy for adult patients with heart failure,” Ravi Tayi, MD, MPH, chief medical officer at American Regent, said in a news release.

Ferric carboxymaltose injection is also indicated for the treatment of iron deficiency anemia in adults and children as young as 1 year of age who have either intolerance or an unsatisfactory response to oral iron, and in adult patients who have nondialysis dependent chronic kidney disease.

The new indication in HF was supported by data from the CONFIRM-HF randomized controlled trial that evaluated the efficacy and safety of ferric carboxymaltose injection in adults with chronic HF and iron deficiency.

In the study, results showed that treatment with ferric carboxymaltose injection significantly improved exercise capacity compared with placebo in iron-deficient patients with HF.  

No new safety signals emerged. The most common treatment emergent adverse events were headache, nausea, hypertension, injection site reactions, hypophosphatemia, and dizziness.

According to the company, ferric carboxymaltose injection has been studied in more than 40 clinical trials that included over 8,800 patients worldwide and has been approved in 86 countries.

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

Linda Bluestein remembers all the doctors who missed, ignored, or incompletely diagnosed her chronic illness.

There was the orthopedic surgeon who noted her hyperextended elbows but failed to check any of her other joints. The gastroenterologist who insisted on performing multiple scoping procedures but wouldn’t discuss how to manage her symptoms. The other surgeon who, after performing arthroscopy on her injured knee, yelled at her: “There is nothing wrong with your knee! You’re fine!” in a room full of people.

And then there was the rheumatologist who said: “Oh, you want something to be wrong with you?”

“No,” she replied, “I want an explanation. I want to keep working. I just want to know why these things keep happening to me.”

The medical frustration she experienced was especially difficult because, like her health care providers, Linda Bluestein has an MD after her name. She is a board-certified anesthesiologist and integrative medicine physician.

Living with a chronic illness is a challenge for any patient. But physicians who are diagnosed with chronic conditions face a unique set of personal and professional issues.

Along with the physically demanding schedule of medical practice, they must cope with what many call a “culture of invincibility” within medicine. Doctors are not supposed to get sick. In fact, the unwritten rule is presenteeism – to function without adequate food or sleep and to never prioritize their own self-care over their dedication to their patients.

Whether their conditions are visible, such as muscular dystrophy and multiple sclerosis, or invisible, such as fibromyalgia and mental illnesses – and now, long COVID – these doctors often meet significant stigma. They fight the assumption that they are less capable than their colleagues.

But they also experience an invaluable benefit: They gain firsthand knowledge of the patient experience, a profound understanding which, they say, enhances how they care for their own patients.
 

What it takes to become a doctor when you have a chronic condition

In short, it’s not easy.

Data from the 2018 National Health Interview Survey show that more than half of U.S. adults had at least one of several chronic conditions, including rheumatoid arthritis, asthma, diabetes, hypertension, and kidney problems. Nearly a third of respondents had more than one condition. But fewer than 5% of medical students and 3% of practicing physicians report having a chronic illness or disability, according to studies from 2019 and 2021.

While that could mean that fewer people with chronic illness enter medicine, cases also exist in which aspiring physicians with conditions were dissuaded from pursuing a career in medicine at all.

Amy Stenehjem, MD, a physical medicine and rehabilitation physician, is one of the exceptions. Diagnosed with several autoimmune-related conditions as a teenager and young adult, Dr. Stenehjem was determined to become a doctor. In her 20s, her health was relatively stable, and she was able to manage medical school and residency. Her training institutions agreed to provide some accommodations that helped her succeed.

“They let me build some flexibility into the training,” Dr. Stenehjem said. “In medical school, when I knew I wasn’t going to be able to do a particular specialty as a career, they let me work with an attending doctor that did not require a lot of on-call time during that particular rotation.”

Dr. Stenehjem specialized in chronic neck and back disorders, fibromyalgia, chronic fatigue syndrome (myalgic encephalomyelitis), and autoimmune-related diseases. She practiced for more than a decade. But in 2011, her condition spiraled. She couldn’t walk a few steps or even sit upright without experiencing dizziness and shortness of breath. She had debilitating fatigue and episodes of fever, rash, headaches, and joint pain.

It would take 7 years and more than 20 doctors to determine Dr. Stenehjem’s multiple diagnoses. In addition to her autoimmune diseases, she was diagnosed with postural orthostatic tachycardia syndrome, autoinflammatory periodic fever syndrome, Lyme disease, and reactivated Epstein-Barr infection.

While she suspects that her providers gave her more “leeway” because she was a physician, many did not show a deep understanding of the severity of her symptoms and the impact those symptoms had.

“When I was practicing, I really didn’t fully understand the impact chronic illness had on my patients,” Dr. Stenehjem said. “Things like chronic dizziness, headaches, fatigue, pain, or brain fog can be really hard to understand unless you’ve experienced these symptoms. When I got sick, I finally realized, ‘Oh my goodness, when a patient says they’re dealing with fatigue, this is not your normal, I’m-super-tired-from-being-on-call fatigue. This is I-can’t-get-out-of-bed fatigue.’ That’s what people with chronic illness often deal with on a daily basis.”
 

Treating the individual

Dr. Stenehjem was aware that her chronic illness would affect her medical career. For Jason Baker, MD, an endocrinologist at Weill Cornell Medicine, New York, it came as a shock. Dr. Baker was a third-year medical student when he experienced increased urination and rapid weight loss. It was only when friends pressed him to visit student health that a blood test revealed type 1 diabetes. Dr. Baker suddenly found himself lying in a hospital bed.

He remembers an attending physician who simply handed him a textbook on diabetic ketoacidosis (DKA) and a resident who informed him that he had kidney damage, which turned out to be untrue. Neither discussed the psychological issues from a frightening diagnosis that would require lifelong, daily management.

“There certainly could have been a bit more empathy from some of the people I dealt with early on,” he said.

Although his training gave him a stark picture of worst-case scenarios, Dr. Baker found that knowledge motivating. “I’d already seen patients come in who had diabetes complications,” Dr. Baker says. “I vowed to never ever get those complications. It was a good balance of fear and motivation.”

Dr. Baker had not planned to specialize in endocrinology, but he quickly realized that his personal diagnosis could help others. Now he often shares his experience with his patients who have diabetes, which he says makes them more comfortable discussing their own problems.

His approach, Dr. Baker explained, is to treat everyone as an individual. Trying to neatly classify patients with chronic illness is a common mistake he notices among physicians.

“There’s a lot of misunderstanding about type 1 versus type 2 [diabetes],” Dr. Baker said, “and trying to categorize people when sometimes people can’t be categorized. That’s really with any chronic condition; there’s no one size fits all.”

Managing his health is still a time-consuming task. At work, he needs breaks to eat, check his blood sugar, or take insulin. “During the workday seeing patients, I have to also remember that I’m a patient,” Dr. Baker said. “I have to be okay with prioritizing my own health. Otherwise I can’t help anybody.”
 

‘I am not the doctor for you’

Chronic diseases such as diabetes or hypertension are familiar to most doctors, and with good management, patients can usually function normally. When chronic conditions become disabling, however, attitudes in the medical field can change.

According to data from the Centers for Disease Control and Prevention and from studies, people with disabilities experience significant disparities and barriers to care. Some of this can be linked to social determinants of health. People with disabilities are more likely to be poor and to rely on Medicare and Medicaid for insurance coverage. But lack of training, unwillingness to provide accommodations, ignorance of legal requirements, and inaccurate assumptions among physicians also play a role.

These are themes that Lisa Iezzoni, MD, a professor of medicine at Harvard Medical School, Boston, has heard from hundreds of patients with disabilities during the more than 25 years that she has conducted research.

In late 2019, Dr. Iezzoni and coinvestigators fielded a national survey of 714 practicing physicians. Only 40.7% reported they were “very confident” that they could provide the same quality of care to patients with disabilities as they do for other patients. And only 56.5% “strongly agreed” that they welcomed these patients into their practices.

The survey was conducted through a series of small focus groups that Dr. Iezzoni held with physicians in 2018. These yielded views that were startling, and in some cases, overtly discriminatory:

• Doctors complained about the “burden” of caring for a patient with a disability.
• They lacked the time or equipment, such as accessible exam tables or weight scales.
• They admitted to inventing excuses for why appointments were not available or routine diagnostic tests were not performed.
• They described being fearful of lawsuits under the Americans with Disabilities Act.

The overall message was summed up in one doctor’s statement: “I am not the doctor for you.”

“Doctors are people too,” Dr. Iezzoni pointed out. “And so they reflect the same prejudices and stigmatized attitudes of the rest of the population. It might be implicit, so they might not be aware of it. [But] it might be explicit.”

Ableism in the medical field is all too familiar to Dr. Iezzoni. She was diagnosed with multiple sclerosis at age 26 during her first year at Harvard Medical School in the early 1980s. Despite symptom flare-ups, Dr. Iezzoni was able to graduate with her class, but many instructors and administrators had little interest in accommodating her physical limitations. In fact, several physicians discouraged her from continuing to train.

Unable to take call, run up flights of stairs, or stand for hours at a time, Dr. Iezzoni remembers being told by a senior surgeon that she shouldn’t become a doctor since she lacked the “most important quality,” which was “24/7 availability.” A hospital CEO informed her: “There are too many doctors in the country right now for us to worry about training a handicapped physician. If that means that some people get left by the wayside, so be it.”

Ultimately, Harvard Medical School declined to write Dr. Iezzoni a letter of recommendation for an internship. She would never practice medicine. “My career was just truncated from the start,” Dr. Iezzoni said. “It never happened because of discrimination.”

She later learned the legal term for her treatment: constructive dismissal.

“The medical school didn’t outright say, ‘Go away. We’re not allowing you to graduate.’ ” Dr. Iezzoni explained. “But they made my life so difficult that I did so voluntarily.”

Dr. Iezzoni graduated in 1984, before the passage of the ADA in 1990, and she refers to her experience as a “ghost from the past,” a historical reminder of how the legal landscape has changed – even though the tendency toward bias may not have.
 

The fight for inclusion

Zainub Dhanani, a fifth-year medical student at Stanford (Calif.) University, won’t forget an interview at one of the other schools to which she applied. The interviewer asked how she expected to be in a hospital all day if she had a chronic illness.

“Does it really make sense?” he wanted to know.

The question shocked her in the moment, but now she sees this type of bias as linked to the inequalities that many marginalized groups face in health care and beyond. That’s also why she believes physician-patients are crucial to improve the quality of care for people with chronic illness and other groups that face discrimination.

Who else, she wonders, could provide that “reaffirming” experience for patients or have that “unique edge” other than a provider who has navigated the same world?

Ms. Dhanani is the executive director and founder of Medical Students With Disability and Chronic Illness, an organization dedicated to empowering these students through advocacy, education, accessibility, and community. The group now has 19 chapters at medical schools across the country.

Ms. Dhanani said she has received excellent accommodations from Stanford for her own condition (which she prefers not to disclose), but all medical schools are not as responsive to students with various physical needs. Her organization offers support and resources to inform these future physicians about their options and rights.

“Disability justice is also racial justice,” Ms. Dhanani stressed. “It’s also environmental justice. It’s also gender and sexuality-based justice. Those compounded layers of biases lead to worse and worse levels of care. As a patient, it’s terrifying. And as a future physician, it’s tragic to know that this is something so pervasive and yet so under-addressed in medicine.”
 

Soldiering on

Unfortunately, for some physicians with chronic illness, there are no practical accommodations that could save their careers in clinical practice.

Dr. Stenehjem now works part-time as a health consultant, helping those with chronic illnesses navigate their health care systems.

Dr. Bluestein offers a similar coaching service to patients with Ehlers-Danlos syndrome (EDS) and other connective tissue and hypermobility disorders. Because of her own EDS, she can no longer practice as an anesthesiologist but instead opened an integrative pain management practice for patients with complex pain conditions..

She believes the idea that doctors are “invincible” needs to change. She recalls the time her former group practice told her in no uncertain terms to “never call in sick.”

The stories she hears from her current clients are similar to her own. She can empathize, knowing firsthand the physical and psychological damage these attitudes can cause.

“When I was at my worst physically, I was also at my worst psychologically,” said Dr. Bluestein. “We tend to think of them as separate, but they go hand in hand. If we can validate people’s experiences rather than disregard them, it has a positive forward cycle, as opposed to the reverse, which is what usually happens.”

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

Linda Bluestein remembers all the doctors who missed, ignored, or incompletely diagnosed her chronic illness.

There was the orthopedic surgeon who noted her hyperextended elbows but failed to check any of her other joints. The gastroenterologist who insisted on performing multiple scoping procedures but wouldn’t discuss how to manage her symptoms. The other surgeon who, after performing arthroscopy on her injured knee, yelled at her: “There is nothing wrong with your knee! You’re fine!” in a room full of people.

And then there was the rheumatologist who said: “Oh, you want something to be wrong with you?”

“No,” she replied, “I want an explanation. I want to keep working. I just want to know why these things keep happening to me.”

The medical frustration she experienced was especially difficult because, like her health care providers, Linda Bluestein has an MD after her name. She is a board-certified anesthesiologist and integrative medicine physician.

Living with a chronic illness is a challenge for any patient. But physicians who are diagnosed with chronic conditions face a unique set of personal and professional issues.

Along with the physically demanding schedule of medical practice, they must cope with what many call a “culture of invincibility” within medicine. Doctors are not supposed to get sick. In fact, the unwritten rule is presenteeism – to function without adequate food or sleep and to never prioritize their own self-care over their dedication to their patients.

Whether their conditions are visible, such as muscular dystrophy and multiple sclerosis, or invisible, such as fibromyalgia and mental illnesses – and now, long COVID – these doctors often meet significant stigma. They fight the assumption that they are less capable than their colleagues.

But they also experience an invaluable benefit: They gain firsthand knowledge of the patient experience, a profound understanding which, they say, enhances how they care for their own patients.
 

What it takes to become a doctor when you have a chronic condition

In short, it’s not easy.

Data from the 2018 National Health Interview Survey show that more than half of U.S. adults had at least one of several chronic conditions, including rheumatoid arthritis, asthma, diabetes, hypertension, and kidney problems. Nearly a third of respondents had more than one condition. But fewer than 5% of medical students and 3% of practicing physicians report having a chronic illness or disability, according to studies from 2019 and 2021.

While that could mean that fewer people with chronic illness enter medicine, cases also exist in which aspiring physicians with conditions were dissuaded from pursuing a career in medicine at all.

Amy Stenehjem, MD, a physical medicine and rehabilitation physician, is one of the exceptions. Diagnosed with several autoimmune-related conditions as a teenager and young adult, Dr. Stenehjem was determined to become a doctor. In her 20s, her health was relatively stable, and she was able to manage medical school and residency. Her training institutions agreed to provide some accommodations that helped her succeed.

“They let me build some flexibility into the training,” Dr. Stenehjem said. “In medical school, when I knew I wasn’t going to be able to do a particular specialty as a career, they let me work with an attending doctor that did not require a lot of on-call time during that particular rotation.”

Dr. Stenehjem specialized in chronic neck and back disorders, fibromyalgia, chronic fatigue syndrome (myalgic encephalomyelitis), and autoimmune-related diseases. She practiced for more than a decade. But in 2011, her condition spiraled. She couldn’t walk a few steps or even sit upright without experiencing dizziness and shortness of breath. She had debilitating fatigue and episodes of fever, rash, headaches, and joint pain.

It would take 7 years and more than 20 doctors to determine Dr. Stenehjem’s multiple diagnoses. In addition to her autoimmune diseases, she was diagnosed with postural orthostatic tachycardia syndrome, autoinflammatory periodic fever syndrome, Lyme disease, and reactivated Epstein-Barr infection.

While she suspects that her providers gave her more “leeway” because she was a physician, many did not show a deep understanding of the severity of her symptoms and the impact those symptoms had.

“When I was practicing, I really didn’t fully understand the impact chronic illness had on my patients,” Dr. Stenehjem said. “Things like chronic dizziness, headaches, fatigue, pain, or brain fog can be really hard to understand unless you’ve experienced these symptoms. When I got sick, I finally realized, ‘Oh my goodness, when a patient says they’re dealing with fatigue, this is not your normal, I’m-super-tired-from-being-on-call fatigue. This is I-can’t-get-out-of-bed fatigue.’ That’s what people with chronic illness often deal with on a daily basis.”
 

Treating the individual

Dr. Stenehjem was aware that her chronic illness would affect her medical career. For Jason Baker, MD, an endocrinologist at Weill Cornell Medicine, New York, it came as a shock. Dr. Baker was a third-year medical student when he experienced increased urination and rapid weight loss. It was only when friends pressed him to visit student health that a blood test revealed type 1 diabetes. Dr. Baker suddenly found himself lying in a hospital bed.

He remembers an attending physician who simply handed him a textbook on diabetic ketoacidosis (DKA) and a resident who informed him that he had kidney damage, which turned out to be untrue. Neither discussed the psychological issues from a frightening diagnosis that would require lifelong, daily management.

“There certainly could have been a bit more empathy from some of the people I dealt with early on,” he said.

Although his training gave him a stark picture of worst-case scenarios, Dr. Baker found that knowledge motivating. “I’d already seen patients come in who had diabetes complications,” Dr. Baker says. “I vowed to never ever get those complications. It was a good balance of fear and motivation.”

Dr. Baker had not planned to specialize in endocrinology, but he quickly realized that his personal diagnosis could help others. Now he often shares his experience with his patients who have diabetes, which he says makes them more comfortable discussing their own problems.

His approach, Dr. Baker explained, is to treat everyone as an individual. Trying to neatly classify patients with chronic illness is a common mistake he notices among physicians.

“There’s a lot of misunderstanding about type 1 versus type 2 [diabetes],” Dr. Baker said, “and trying to categorize people when sometimes people can’t be categorized. That’s really with any chronic condition; there’s no one size fits all.”

Managing his health is still a time-consuming task. At work, he needs breaks to eat, check his blood sugar, or take insulin. “During the workday seeing patients, I have to also remember that I’m a patient,” Dr. Baker said. “I have to be okay with prioritizing my own health. Otherwise I can’t help anybody.”
 

‘I am not the doctor for you’

Chronic diseases such as diabetes or hypertension are familiar to most doctors, and with good management, patients can usually function normally. When chronic conditions become disabling, however, attitudes in the medical field can change.

According to data from the Centers for Disease Control and Prevention and from studies, people with disabilities experience significant disparities and barriers to care. Some of this can be linked to social determinants of health. People with disabilities are more likely to be poor and to rely on Medicare and Medicaid for insurance coverage. But lack of training, unwillingness to provide accommodations, ignorance of legal requirements, and inaccurate assumptions among physicians also play a role.

These are themes that Lisa Iezzoni, MD, a professor of medicine at Harvard Medical School, Boston, has heard from hundreds of patients with disabilities during the more than 25 years that she has conducted research.

In late 2019, Dr. Iezzoni and coinvestigators fielded a national survey of 714 practicing physicians. Only 40.7% reported they were “very confident” that they could provide the same quality of care to patients with disabilities as they do for other patients. And only 56.5% “strongly agreed” that they welcomed these patients into their practices.

The survey was conducted through a series of small focus groups that Dr. Iezzoni held with physicians in 2018. These yielded views that were startling, and in some cases, overtly discriminatory:

• Doctors complained about the “burden” of caring for a patient with a disability.
• They lacked the time or equipment, such as accessible exam tables or weight scales.
• They admitted to inventing excuses for why appointments were not available or routine diagnostic tests were not performed.
• They described being fearful of lawsuits under the Americans with Disabilities Act.

The overall message was summed up in one doctor’s statement: “I am not the doctor for you.”

“Doctors are people too,” Dr. Iezzoni pointed out. “And so they reflect the same prejudices and stigmatized attitudes of the rest of the population. It might be implicit, so they might not be aware of it. [But] it might be explicit.”

Ableism in the medical field is all too familiar to Dr. Iezzoni. She was diagnosed with multiple sclerosis at age 26 during her first year at Harvard Medical School in the early 1980s. Despite symptom flare-ups, Dr. Iezzoni was able to graduate with her class, but many instructors and administrators had little interest in accommodating her physical limitations. In fact, several physicians discouraged her from continuing to train.

Unable to take call, run up flights of stairs, or stand for hours at a time, Dr. Iezzoni remembers being told by a senior surgeon that she shouldn’t become a doctor since she lacked the “most important quality,” which was “24/7 availability.” A hospital CEO informed her: “There are too many doctors in the country right now for us to worry about training a handicapped physician. If that means that some people get left by the wayside, so be it.”

Ultimately, Harvard Medical School declined to write Dr. Iezzoni a letter of recommendation for an internship. She would never practice medicine. “My career was just truncated from the start,” Dr. Iezzoni said. “It never happened because of discrimination.”

She later learned the legal term for her treatment: constructive dismissal.

“The medical school didn’t outright say, ‘Go away. We’re not allowing you to graduate.’ ” Dr. Iezzoni explained. “But they made my life so difficult that I did so voluntarily.”

Dr. Iezzoni graduated in 1984, before the passage of the ADA in 1990, and she refers to her experience as a “ghost from the past,” a historical reminder of how the legal landscape has changed – even though the tendency toward bias may not have.
 

The fight for inclusion

Zainub Dhanani, a fifth-year medical student at Stanford (Calif.) University, won’t forget an interview at one of the other schools to which she applied. The interviewer asked how she expected to be in a hospital all day if she had a chronic illness.

“Does it really make sense?” he wanted to know.

The question shocked her in the moment, but now she sees this type of bias as linked to the inequalities that many marginalized groups face in health care and beyond. That’s also why she believes physician-patients are crucial to improve the quality of care for people with chronic illness and other groups that face discrimination.

Who else, she wonders, could provide that “reaffirming” experience for patients or have that “unique edge” other than a provider who has navigated the same world?

Ms. Dhanani is the executive director and founder of Medical Students With Disability and Chronic Illness, an organization dedicated to empowering these students through advocacy, education, accessibility, and community. The group now has 19 chapters at medical schools across the country.

Ms. Dhanani said she has received excellent accommodations from Stanford for her own condition (which she prefers not to disclose), but all medical schools are not as responsive to students with various physical needs. Her organization offers support and resources to inform these future physicians about their options and rights.

“Disability justice is also racial justice,” Ms. Dhanani stressed. “It’s also environmental justice. It’s also gender and sexuality-based justice. Those compounded layers of biases lead to worse and worse levels of care. As a patient, it’s terrifying. And as a future physician, it’s tragic to know that this is something so pervasive and yet so under-addressed in medicine.”
 

Soldiering on

Unfortunately, for some physicians with chronic illness, there are no practical accommodations that could save their careers in clinical practice.

Dr. Stenehjem now works part-time as a health consultant, helping those with chronic illnesses navigate their health care systems.

Dr. Bluestein offers a similar coaching service to patients with Ehlers-Danlos syndrome (EDS) and other connective tissue and hypermobility disorders. Because of her own EDS, she can no longer practice as an anesthesiologist but instead opened an integrative pain management practice for patients with complex pain conditions..

She believes the idea that doctors are “invincible” needs to change. She recalls the time her former group practice told her in no uncertain terms to “never call in sick.”

The stories she hears from her current clients are similar to her own. She can empathize, knowing firsthand the physical and psychological damage these attitudes can cause.

“When I was at my worst physically, I was also at my worst psychologically,” said Dr. Bluestein. “We tend to think of them as separate, but they go hand in hand. If we can validate people’s experiences rather than disregard them, it has a positive forward cycle, as opposed to the reverse, which is what usually happens.”

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

Linda Bluestein remembers all the doctors who missed, ignored, or incompletely diagnosed her chronic illness.

There was the orthopedic surgeon who noted her hyperextended elbows but failed to check any of her other joints. The gastroenterologist who insisted on performing multiple scoping procedures but wouldn’t discuss how to manage her symptoms. The other surgeon who, after performing arthroscopy on her injured knee, yelled at her: “There is nothing wrong with your knee! You’re fine!” in a room full of people.

And then there was the rheumatologist who said: “Oh, you want something to be wrong with you?”

“No,” she replied, “I want an explanation. I want to keep working. I just want to know why these things keep happening to me.”

The medical frustration she experienced was especially difficult because, like her health care providers, Linda Bluestein has an MD after her name. She is a board-certified anesthesiologist and integrative medicine physician.

Living with a chronic illness is a challenge for any patient. But physicians who are diagnosed with chronic conditions face a unique set of personal and professional issues.

Along with the physically demanding schedule of medical practice, they must cope with what many call a “culture of invincibility” within medicine. Doctors are not supposed to get sick. In fact, the unwritten rule is presenteeism – to function without adequate food or sleep and to never prioritize their own self-care over their dedication to their patients.

Whether their conditions are visible, such as muscular dystrophy and multiple sclerosis, or invisible, such as fibromyalgia and mental illnesses – and now, long COVID – these doctors often meet significant stigma. They fight the assumption that they are less capable than their colleagues.

But they also experience an invaluable benefit: They gain firsthand knowledge of the patient experience, a profound understanding which, they say, enhances how they care for their own patients.
 

What it takes to become a doctor when you have a chronic condition

In short, it’s not easy.

Data from the 2018 National Health Interview Survey show that more than half of U.S. adults had at least one of several chronic conditions, including rheumatoid arthritis, asthma, diabetes, hypertension, and kidney problems. Nearly a third of respondents had more than one condition. But fewer than 5% of medical students and 3% of practicing physicians report having a chronic illness or disability, according to studies from 2019 and 2021.

While that could mean that fewer people with chronic illness enter medicine, cases also exist in which aspiring physicians with conditions were dissuaded from pursuing a career in medicine at all.

Amy Stenehjem, MD, a physical medicine and rehabilitation physician, is one of the exceptions. Diagnosed with several autoimmune-related conditions as a teenager and young adult, Dr. Stenehjem was determined to become a doctor. In her 20s, her health was relatively stable, and she was able to manage medical school and residency. Her training institutions agreed to provide some accommodations that helped her succeed.

“They let me build some flexibility into the training,” Dr. Stenehjem said. “In medical school, when I knew I wasn’t going to be able to do a particular specialty as a career, they let me work with an attending doctor that did not require a lot of on-call time during that particular rotation.”

Dr. Stenehjem specialized in chronic neck and back disorders, fibromyalgia, chronic fatigue syndrome (myalgic encephalomyelitis), and autoimmune-related diseases. She practiced for more than a decade. But in 2011, her condition spiraled. She couldn’t walk a few steps or even sit upright without experiencing dizziness and shortness of breath. She had debilitating fatigue and episodes of fever, rash, headaches, and joint pain.

It would take 7 years and more than 20 doctors to determine Dr. Stenehjem’s multiple diagnoses. In addition to her autoimmune diseases, she was diagnosed with postural orthostatic tachycardia syndrome, autoinflammatory periodic fever syndrome, Lyme disease, and reactivated Epstein-Barr infection.

While she suspects that her providers gave her more “leeway” because she was a physician, many did not show a deep understanding of the severity of her symptoms and the impact those symptoms had.

“When I was practicing, I really didn’t fully understand the impact chronic illness had on my patients,” Dr. Stenehjem said. “Things like chronic dizziness, headaches, fatigue, pain, or brain fog can be really hard to understand unless you’ve experienced these symptoms. When I got sick, I finally realized, ‘Oh my goodness, when a patient says they’re dealing with fatigue, this is not your normal, I’m-super-tired-from-being-on-call fatigue. This is I-can’t-get-out-of-bed fatigue.’ That’s what people with chronic illness often deal with on a daily basis.”
 

Treating the individual

Dr. Stenehjem was aware that her chronic illness would affect her medical career. For Jason Baker, MD, an endocrinologist at Weill Cornell Medicine, New York, it came as a shock. Dr. Baker was a third-year medical student when he experienced increased urination and rapid weight loss. It was only when friends pressed him to visit student health that a blood test revealed type 1 diabetes. Dr. Baker suddenly found himself lying in a hospital bed.

He remembers an attending physician who simply handed him a textbook on diabetic ketoacidosis (DKA) and a resident who informed him that he had kidney damage, which turned out to be untrue. Neither discussed the psychological issues from a frightening diagnosis that would require lifelong, daily management.

“There certainly could have been a bit more empathy from some of the people I dealt with early on,” he said.

Although his training gave him a stark picture of worst-case scenarios, Dr. Baker found that knowledge motivating. “I’d already seen patients come in who had diabetes complications,” Dr. Baker says. “I vowed to never ever get those complications. It was a good balance of fear and motivation.”

Dr. Baker had not planned to specialize in endocrinology, but he quickly realized that his personal diagnosis could help others. Now he often shares his experience with his patients who have diabetes, which he says makes them more comfortable discussing their own problems.

His approach, Dr. Baker explained, is to treat everyone as an individual. Trying to neatly classify patients with chronic illness is a common mistake he notices among physicians.

“There’s a lot of misunderstanding about type 1 versus type 2 [diabetes],” Dr. Baker said, “and trying to categorize people when sometimes people can’t be categorized. That’s really with any chronic condition; there’s no one size fits all.”

Managing his health is still a time-consuming task. At work, he needs breaks to eat, check his blood sugar, or take insulin. “During the workday seeing patients, I have to also remember that I’m a patient,” Dr. Baker said. “I have to be okay with prioritizing my own health. Otherwise I can’t help anybody.”
 

‘I am not the doctor for you’

Chronic diseases such as diabetes or hypertension are familiar to most doctors, and with good management, patients can usually function normally. When chronic conditions become disabling, however, attitudes in the medical field can change.

According to data from the Centers for Disease Control and Prevention and from studies, people with disabilities experience significant disparities and barriers to care. Some of this can be linked to social determinants of health. People with disabilities are more likely to be poor and to rely on Medicare and Medicaid for insurance coverage. But lack of training, unwillingness to provide accommodations, ignorance of legal requirements, and inaccurate assumptions among physicians also play a role.

These are themes that Lisa Iezzoni, MD, a professor of medicine at Harvard Medical School, Boston, has heard from hundreds of patients with disabilities during the more than 25 years that she has conducted research.

In late 2019, Dr. Iezzoni and coinvestigators fielded a national survey of 714 practicing physicians. Only 40.7% reported they were “very confident” that they could provide the same quality of care to patients with disabilities as they do for other patients. And only 56.5% “strongly agreed” that they welcomed these patients into their practices.

The survey was conducted through a series of small focus groups that Dr. Iezzoni held with physicians in 2018. These yielded views that were startling, and in some cases, overtly discriminatory:

• Doctors complained about the “burden” of caring for a patient with a disability.
• They lacked the time or equipment, such as accessible exam tables or weight scales.
• They admitted to inventing excuses for why appointments were not available or routine diagnostic tests were not performed.
• They described being fearful of lawsuits under the Americans with Disabilities Act.

The overall message was summed up in one doctor’s statement: “I am not the doctor for you.”

“Doctors are people too,” Dr. Iezzoni pointed out. “And so they reflect the same prejudices and stigmatized attitudes of the rest of the population. It might be implicit, so they might not be aware of it. [But] it might be explicit.”

Ableism in the medical field is all too familiar to Dr. Iezzoni. She was diagnosed with multiple sclerosis at age 26 during her first year at Harvard Medical School in the early 1980s. Despite symptom flare-ups, Dr. Iezzoni was able to graduate with her class, but many instructors and administrators had little interest in accommodating her physical limitations. In fact, several physicians discouraged her from continuing to train.

Unable to take call, run up flights of stairs, or stand for hours at a time, Dr. Iezzoni remembers being told by a senior surgeon that she shouldn’t become a doctor since she lacked the “most important quality,” which was “24/7 availability.” A hospital CEO informed her: “There are too many doctors in the country right now for us to worry about training a handicapped physician. If that means that some people get left by the wayside, so be it.”

Ultimately, Harvard Medical School declined to write Dr. Iezzoni a letter of recommendation for an internship. She would never practice medicine. “My career was just truncated from the start,” Dr. Iezzoni said. “It never happened because of discrimination.”

She later learned the legal term for her treatment: constructive dismissal.

“The medical school didn’t outright say, ‘Go away. We’re not allowing you to graduate.’ ” Dr. Iezzoni explained. “But they made my life so difficult that I did so voluntarily.”

Dr. Iezzoni graduated in 1984, before the passage of the ADA in 1990, and she refers to her experience as a “ghost from the past,” a historical reminder of how the legal landscape has changed – even though the tendency toward bias may not have.
 

The fight for inclusion

Zainub Dhanani, a fifth-year medical student at Stanford (Calif.) University, won’t forget an interview at one of the other schools to which she applied. The interviewer asked how she expected to be in a hospital all day if she had a chronic illness.

“Does it really make sense?” he wanted to know.

The question shocked her in the moment, but now she sees this type of bias as linked to the inequalities that many marginalized groups face in health care and beyond. That’s also why she believes physician-patients are crucial to improve the quality of care for people with chronic illness and other groups that face discrimination.

Who else, she wonders, could provide that “reaffirming” experience for patients or have that “unique edge” other than a provider who has navigated the same world?

Ms. Dhanani is the executive director and founder of Medical Students With Disability and Chronic Illness, an organization dedicated to empowering these students through advocacy, education, accessibility, and community. The group now has 19 chapters at medical schools across the country.

Ms. Dhanani said she has received excellent accommodations from Stanford for her own condition (which she prefers not to disclose), but all medical schools are not as responsive to students with various physical needs. Her organization offers support and resources to inform these future physicians about their options and rights.

“Disability justice is also racial justice,” Ms. Dhanani stressed. “It’s also environmental justice. It’s also gender and sexuality-based justice. Those compounded layers of biases lead to worse and worse levels of care. As a patient, it’s terrifying. And as a future physician, it’s tragic to know that this is something so pervasive and yet so under-addressed in medicine.”
 

Soldiering on

Unfortunately, for some physicians with chronic illness, there are no practical accommodations that could save their careers in clinical practice.

Dr. Stenehjem now works part-time as a health consultant, helping those with chronic illnesses navigate their health care systems.

Dr. Bluestein offers a similar coaching service to patients with Ehlers-Danlos syndrome (EDS) and other connective tissue and hypermobility disorders. Because of her own EDS, she can no longer practice as an anesthesiologist but instead opened an integrative pain management practice for patients with complex pain conditions..

She believes the idea that doctors are “invincible” needs to change. She recalls the time her former group practice told her in no uncertain terms to “never call in sick.”

The stories she hears from her current clients are similar to her own. She can empathize, knowing firsthand the physical and psychological damage these attitudes can cause.

“When I was at my worst physically, I was also at my worst psychologically,” said Dr. Bluestein. “We tend to think of them as separate, but they go hand in hand. If we can validate people’s experiences rather than disregard them, it has a positive forward cycle, as opposed to the reverse, which is what usually happens.”

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

More than 600,000 Americans have lost Medicaid coverage since pandemic protections ended on April 1. And a KFF Health News analysis of state data shows the vast majority were removed from state rolls for not completing paperwork.

Under normal circumstances, states review their Medicaid enrollment lists regularly to ensure every recipient qualifies for coverage. But because of a nationwide pause in those reviews during the pandemic, the health insurance program for low-income and disabled Americans kept people covered even if they no longer qualified.

Now, in what’s known as the Medicaid unwinding, states are combing through rolls and deciding who stays and who goes. People who are no longer eligible or don’t complete paperwork in time will be dropped.

The overwhelming majority of people who have lost coverage in most states were dropped because of technicalities, not because state officials determined they no longer meet Medicaid income limits. Four out of every five people dropped so far either never returned the paperwork or omitted required documents, according to a KFF Health News analysis of data from 11 states that provided details on recent cancellations. Now, lawmakers and advocates are expressing alarm over the volume of people losing coverage and, in some states, calling to pause the process.

KFF Health News sought data from the 19 states that started cancellations by May 1. Based on records from 14 states that provided detailed numbers, either in response to a public records request or by posting online, 36% of people whose eligibility was reviewed have been disenrolled.

In Indiana, 53,000 residents lost coverage in the first month of the unwinding, 89% for procedural reasons like not returning renewal forms. State Rep. Ed Clere, a Republican, expressed dismay at those “staggering numbers” in a May 24 Medicaid advisory group meeting, repeatedly questioning state officials about forms mailed to out-of-date addresses and urging them to give people more than 2 weeks’ notice before canceling their coverage.

Rep. Clere warned that the cancellations set in motion an avoidable revolving door. Some people dropped from Medicaid will have to forgo filling prescriptions and cancel doctor visits because they can’t afford care. Months down the line, after untreated chronic illnesses spiral out of control, they’ll end up in the emergency room where social workers will need to again help them join the program, he said.

Before the unwinding, more than one in four Americans – 93 million – were covered by Medicaid or CHIP, the Children’s Health Insurance Program, according to KFF Health News’ analysis of the latest enrollment data. Half of all kids are covered by the programs.

About 15 million people will be dropped over the next year as states review participants’ eligibility in monthly tranches.

Most people will find health coverage through new jobs or qualify for subsidized plans through the Affordable Care Act. But millions of others, including many children, will become uninsured and unable to afford basic prescriptions or preventive care. The uninsured rate among those under 65 is projected to rise from a historical low of 8.3% today to 9.3% next year, according to the Congressional Budget Office.

Because each state is handling the unwinding differently, the share of enrollees dropped in the first weeks varies widely.

Several states are first reviewing people officials believe are no longer eligible or who haven’t recently used their insurance. High cancellation rates in those states should level out as the agencies move on to people who likely still qualify.

In Utah, nearly 56% of people included in early reviews were dropped. In New Hampshire, 44% received cancellation letters within the first 2 months – almost all for procedural reasons, like not returning paperwork.

But New Hampshire officials found that thousands of people who didn’t fill out the forms indeed earn too much to qualify, according to Henry Lipman, the state’s Medicaid director. They would have been denied anyway. Even so, more people than he expected are not returning renewal forms. “That tells us that we need to change up our strategy,” said Mr. Lipman.

In other states, like Virginia and Nebraska, which aren’t prioritizing renewals by likely eligibility, about 90% have been renewed.

Because of the 3-year pause in renewals, many people on Medicaid have never been through the process or aren’t aware they may need to fill out long verification forms, as a recent KFF poll found. Some people moved and didn’t update their contact information.

And while agencies are required to assist enrollees who don’t speak English well, many are sending the forms in only a few common languages.

Tens of thousands of children are losing coverage, as researchers have warned, even though some may still qualify for Medicaid or CHIP. In its first month of reviews, South Dakota ended coverage for 10% of all Medicaid and CHIP enrollees in the state. More than half of them were children. In Arkansas, about 40% were kids.

Many parents don’t know that limits on household income are significantly higher for children than adults. Parents should fill out renewal forms even if they don’t qualify themselves, said Joan Alker, executive director of the Georgetown University Center for Children and Families, Washington.

New Hampshire has moved most families with children to the end of the review process. Mr. Lipman said his biggest worry is that a child will end up uninsured. Florida also planned to push kids with serious health conditions and other vulnerable groups to the end of the review line.

But according to Miriam Harmatz, advocacy director and founder of the Florida Health Justice Project, state officials sent cancellation letters to several clients with disabled children who probably still qualify. She’s helping those families appeal.

Nearly 250,000 Floridians reviewed in the first month of the unwinding lost coverage, 82% of them for reasons like incomplete paperwork, the state reported to federal authorities. House Democrats from the state petitioned Republican Gov. Ron DeSantis to pause the unwinding.

Advocacy coalitions in both Florida and Arkansas also have called for investigations into the review process and a pause on cancellations.

The state is contacting enrollees by phone, email, and text, and continues to process late applications, said Tori Cuddy, a spokesperson for the Florida Department of Children and Families. Ms. Cuddy did not respond to questions about issues raised in the petitions.

Federal officials are investigating those complaints and any other problems that emerge, said Dan Tsai, director of the Center for Medicaid & CHIP Services. “If we find that the rules are not being followed, we will take action.”

His agency has directed states to automatically reenroll residents using data from other government programs like unemployment and food assistance when possible. Anyone who can’t be approved through that process must act quickly.

“For the past 3 years, people have been told to ignore the mail around this, that the renewal was not going to lead to a termination.” Suddenly that mail matters, he said.

Federal law requires states to tell people why they’re losing Medicaid coverage and how to appeal the decision.

Ms. Harmatz said some cancellation notices in Florida are vague and could violate due process rules. Letters that she’s seen say “your Medicaid for this period is ending” rather than providing a specific reason for disenrollment, like having too high an income or incomplete paperwork.
If a person requests a hearing before their cancellation takes effect, they can stay covered during the appeals process. Even after being disenrolled, many still have a 90-day window to restore coverage.

In New Hampshire, 13% of people deemed ineligible in the first month have asked for extra time to provide the necessary records. “If you’re eligible for Medicaid, we don’t want you to lose it,” said Mr. Lipman.

Rep. Clere pushed Indiana’s Medicaid officials during the May meeting to immediately make changes to avoid people unnecessarily becoming uninsured. One official responded that they’ll learn and improve over time.

“I’m just concerned that we’re going to be ‘learning’ as a result of people losing coverage,” Rep. Clere replied. “So I don’t want to learn at their expense.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

More than 600,000 Americans have lost Medicaid coverage since pandemic protections ended on April 1. And a KFF Health News analysis of state data shows the vast majority were removed from state rolls for not completing paperwork.

Under normal circumstances, states review their Medicaid enrollment lists regularly to ensure every recipient qualifies for coverage. But because of a nationwide pause in those reviews during the pandemic, the health insurance program for low-income and disabled Americans kept people covered even if they no longer qualified.

Now, in what’s known as the Medicaid unwinding, states are combing through rolls and deciding who stays and who goes. People who are no longer eligible or don’t complete paperwork in time will be dropped.

The overwhelming majority of people who have lost coverage in most states were dropped because of technicalities, not because state officials determined they no longer meet Medicaid income limits. Four out of every five people dropped so far either never returned the paperwork or omitted required documents, according to a KFF Health News analysis of data from 11 states that provided details on recent cancellations. Now, lawmakers and advocates are expressing alarm over the volume of people losing coverage and, in some states, calling to pause the process.

KFF Health News sought data from the 19 states that started cancellations by May 1. Based on records from 14 states that provided detailed numbers, either in response to a public records request or by posting online, 36% of people whose eligibility was reviewed have been disenrolled.

In Indiana, 53,000 residents lost coverage in the first month of the unwinding, 89% for procedural reasons like not returning renewal forms. State Rep. Ed Clere, a Republican, expressed dismay at those “staggering numbers” in a May 24 Medicaid advisory group meeting, repeatedly questioning state officials about forms mailed to out-of-date addresses and urging them to give people more than 2 weeks’ notice before canceling their coverage.

Rep. Clere warned that the cancellations set in motion an avoidable revolving door. Some people dropped from Medicaid will have to forgo filling prescriptions and cancel doctor visits because they can’t afford care. Months down the line, after untreated chronic illnesses spiral out of control, they’ll end up in the emergency room where social workers will need to again help them join the program, he said.

Before the unwinding, more than one in four Americans – 93 million – were covered by Medicaid or CHIP, the Children’s Health Insurance Program, according to KFF Health News’ analysis of the latest enrollment data. Half of all kids are covered by the programs.

About 15 million people will be dropped over the next year as states review participants’ eligibility in monthly tranches.

Most people will find health coverage through new jobs or qualify for subsidized plans through the Affordable Care Act. But millions of others, including many children, will become uninsured and unable to afford basic prescriptions or preventive care. The uninsured rate among those under 65 is projected to rise from a historical low of 8.3% today to 9.3% next year, according to the Congressional Budget Office.

Because each state is handling the unwinding differently, the share of enrollees dropped in the first weeks varies widely.

Several states are first reviewing people officials believe are no longer eligible or who haven’t recently used their insurance. High cancellation rates in those states should level out as the agencies move on to people who likely still qualify.

In Utah, nearly 56% of people included in early reviews were dropped. In New Hampshire, 44% received cancellation letters within the first 2 months – almost all for procedural reasons, like not returning paperwork.

But New Hampshire officials found that thousands of people who didn’t fill out the forms indeed earn too much to qualify, according to Henry Lipman, the state’s Medicaid director. They would have been denied anyway. Even so, more people than he expected are not returning renewal forms. “That tells us that we need to change up our strategy,” said Mr. Lipman.

In other states, like Virginia and Nebraska, which aren’t prioritizing renewals by likely eligibility, about 90% have been renewed.

Because of the 3-year pause in renewals, many people on Medicaid have never been through the process or aren’t aware they may need to fill out long verification forms, as a recent KFF poll found. Some people moved and didn’t update their contact information.

And while agencies are required to assist enrollees who don’t speak English well, many are sending the forms in only a few common languages.

Tens of thousands of children are losing coverage, as researchers have warned, even though some may still qualify for Medicaid or CHIP. In its first month of reviews, South Dakota ended coverage for 10% of all Medicaid and CHIP enrollees in the state. More than half of them were children. In Arkansas, about 40% were kids.

Many parents don’t know that limits on household income are significantly higher for children than adults. Parents should fill out renewal forms even if they don’t qualify themselves, said Joan Alker, executive director of the Georgetown University Center for Children and Families, Washington.

New Hampshire has moved most families with children to the end of the review process. Mr. Lipman said his biggest worry is that a child will end up uninsured. Florida also planned to push kids with serious health conditions and other vulnerable groups to the end of the review line.

But according to Miriam Harmatz, advocacy director and founder of the Florida Health Justice Project, state officials sent cancellation letters to several clients with disabled children who probably still qualify. She’s helping those families appeal.

Nearly 250,000 Floridians reviewed in the first month of the unwinding lost coverage, 82% of them for reasons like incomplete paperwork, the state reported to federal authorities. House Democrats from the state petitioned Republican Gov. Ron DeSantis to pause the unwinding.

Advocacy coalitions in both Florida and Arkansas also have called for investigations into the review process and a pause on cancellations.

The state is contacting enrollees by phone, email, and text, and continues to process late applications, said Tori Cuddy, a spokesperson for the Florida Department of Children and Families. Ms. Cuddy did not respond to questions about issues raised in the petitions.

Federal officials are investigating those complaints and any other problems that emerge, said Dan Tsai, director of the Center for Medicaid & CHIP Services. “If we find that the rules are not being followed, we will take action.”

His agency has directed states to automatically reenroll residents using data from other government programs like unemployment and food assistance when possible. Anyone who can’t be approved through that process must act quickly.

“For the past 3 years, people have been told to ignore the mail around this, that the renewal was not going to lead to a termination.” Suddenly that mail matters, he said.

Federal law requires states to tell people why they’re losing Medicaid coverage and how to appeal the decision.

Ms. Harmatz said some cancellation notices in Florida are vague and could violate due process rules. Letters that she’s seen say “your Medicaid for this period is ending” rather than providing a specific reason for disenrollment, like having too high an income or incomplete paperwork.
If a person requests a hearing before their cancellation takes effect, they can stay covered during the appeals process. Even after being disenrolled, many still have a 90-day window to restore coverage.

In New Hampshire, 13% of people deemed ineligible in the first month have asked for extra time to provide the necessary records. “If you’re eligible for Medicaid, we don’t want you to lose it,” said Mr. Lipman.

Rep. Clere pushed Indiana’s Medicaid officials during the May meeting to immediately make changes to avoid people unnecessarily becoming uninsured. One official responded that they’ll learn and improve over time.

“I’m just concerned that we’re going to be ‘learning’ as a result of people losing coverage,” Rep. Clere replied. “So I don’t want to learn at their expense.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

More than 600,000 Americans have lost Medicaid coverage since pandemic protections ended on April 1. And a KFF Health News analysis of state data shows the vast majority were removed from state rolls for not completing paperwork.

Under normal circumstances, states review their Medicaid enrollment lists regularly to ensure every recipient qualifies for coverage. But because of a nationwide pause in those reviews during the pandemic, the health insurance program for low-income and disabled Americans kept people covered even if they no longer qualified.

Now, in what’s known as the Medicaid unwinding, states are combing through rolls and deciding who stays and who goes. People who are no longer eligible or don’t complete paperwork in time will be dropped.

The overwhelming majority of people who have lost coverage in most states were dropped because of technicalities, not because state officials determined they no longer meet Medicaid income limits. Four out of every five people dropped so far either never returned the paperwork or omitted required documents, according to a KFF Health News analysis of data from 11 states that provided details on recent cancellations. Now, lawmakers and advocates are expressing alarm over the volume of people losing coverage and, in some states, calling to pause the process.

KFF Health News sought data from the 19 states that started cancellations by May 1. Based on records from 14 states that provided detailed numbers, either in response to a public records request or by posting online, 36% of people whose eligibility was reviewed have been disenrolled.

In Indiana, 53,000 residents lost coverage in the first month of the unwinding, 89% for procedural reasons like not returning renewal forms. State Rep. Ed Clere, a Republican, expressed dismay at those “staggering numbers” in a May 24 Medicaid advisory group meeting, repeatedly questioning state officials about forms mailed to out-of-date addresses and urging them to give people more than 2 weeks’ notice before canceling their coverage.

Rep. Clere warned that the cancellations set in motion an avoidable revolving door. Some people dropped from Medicaid will have to forgo filling prescriptions and cancel doctor visits because they can’t afford care. Months down the line, after untreated chronic illnesses spiral out of control, they’ll end up in the emergency room where social workers will need to again help them join the program, he said.

Before the unwinding, more than one in four Americans – 93 million – were covered by Medicaid or CHIP, the Children’s Health Insurance Program, according to KFF Health News’ analysis of the latest enrollment data. Half of all kids are covered by the programs.

About 15 million people will be dropped over the next year as states review participants’ eligibility in monthly tranches.

Most people will find health coverage through new jobs or qualify for subsidized plans through the Affordable Care Act. But millions of others, including many children, will become uninsured and unable to afford basic prescriptions or preventive care. The uninsured rate among those under 65 is projected to rise from a historical low of 8.3% today to 9.3% next year, according to the Congressional Budget Office.

Because each state is handling the unwinding differently, the share of enrollees dropped in the first weeks varies widely.

Several states are first reviewing people officials believe are no longer eligible or who haven’t recently used their insurance. High cancellation rates in those states should level out as the agencies move on to people who likely still qualify.

In Utah, nearly 56% of people included in early reviews were dropped. In New Hampshire, 44% received cancellation letters within the first 2 months – almost all for procedural reasons, like not returning paperwork.

But New Hampshire officials found that thousands of people who didn’t fill out the forms indeed earn too much to qualify, according to Henry Lipman, the state’s Medicaid director. They would have been denied anyway. Even so, more people than he expected are not returning renewal forms. “That tells us that we need to change up our strategy,” said Mr. Lipman.

In other states, like Virginia and Nebraska, which aren’t prioritizing renewals by likely eligibility, about 90% have been renewed.

Because of the 3-year pause in renewals, many people on Medicaid have never been through the process or aren’t aware they may need to fill out long verification forms, as a recent KFF poll found. Some people moved and didn’t update their contact information.

And while agencies are required to assist enrollees who don’t speak English well, many are sending the forms in only a few common languages.

Tens of thousands of children are losing coverage, as researchers have warned, even though some may still qualify for Medicaid or CHIP. In its first month of reviews, South Dakota ended coverage for 10% of all Medicaid and CHIP enrollees in the state. More than half of them were children. In Arkansas, about 40% were kids.

Many parents don’t know that limits on household income are significantly higher for children than adults. Parents should fill out renewal forms even if they don’t qualify themselves, said Joan Alker, executive director of the Georgetown University Center for Children and Families, Washington.

New Hampshire has moved most families with children to the end of the review process. Mr. Lipman said his biggest worry is that a child will end up uninsured. Florida also planned to push kids with serious health conditions and other vulnerable groups to the end of the review line.

But according to Miriam Harmatz, advocacy director and founder of the Florida Health Justice Project, state officials sent cancellation letters to several clients with disabled children who probably still qualify. She’s helping those families appeal.

Nearly 250,000 Floridians reviewed in the first month of the unwinding lost coverage, 82% of them for reasons like incomplete paperwork, the state reported to federal authorities. House Democrats from the state petitioned Republican Gov. Ron DeSantis to pause the unwinding.

Advocacy coalitions in both Florida and Arkansas also have called for investigations into the review process and a pause on cancellations.

The state is contacting enrollees by phone, email, and text, and continues to process late applications, said Tori Cuddy, a spokesperson for the Florida Department of Children and Families. Ms. Cuddy did not respond to questions about issues raised in the petitions.

Federal officials are investigating those complaints and any other problems that emerge, said Dan Tsai, director of the Center for Medicaid & CHIP Services. “If we find that the rules are not being followed, we will take action.”

His agency has directed states to automatically reenroll residents using data from other government programs like unemployment and food assistance when possible. Anyone who can’t be approved through that process must act quickly.

“For the past 3 years, people have been told to ignore the mail around this, that the renewal was not going to lead to a termination.” Suddenly that mail matters, he said.

Federal law requires states to tell people why they’re losing Medicaid coverage and how to appeal the decision.

Ms. Harmatz said some cancellation notices in Florida are vague and could violate due process rules. Letters that she’s seen say “your Medicaid for this period is ending” rather than providing a specific reason for disenrollment, like having too high an income or incomplete paperwork.
If a person requests a hearing before their cancellation takes effect, they can stay covered during the appeals process. Even after being disenrolled, many still have a 90-day window to restore coverage.

In New Hampshire, 13% of people deemed ineligible in the first month have asked for extra time to provide the necessary records. “If you’re eligible for Medicaid, we don’t want you to lose it,” said Mr. Lipman.

Rep. Clere pushed Indiana’s Medicaid officials during the May meeting to immediately make changes to avoid people unnecessarily becoming uninsured. One official responded that they’ll learn and improve over time.

“I’m just concerned that we’re going to be ‘learning’ as a result of people losing coverage,” Rep. Clere replied. “So I don’t want to learn at their expense.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

MANNHEIM, Germany – Lomitapide, which reduces lipoprotein production in the liver, could help manage pediatric homozygous familial hypercholesterolemia (HoFH), suggest results of a trial that showed large reductions in circulating lipids.

The research was presented May 23 at the 91st European Atherosclerosis Society Congress.

Lomitapide inhibits microsomal triglyceride transfer protein, which plays a key role in apolipoprotein B-containing lipoprotein assembly and secretion in the liver and intestines. Crucially, the drug acts independently of the LDL cholesterol receptor.

It was approved in December 2012 by the U.S. Food and Drug Administration for use in adults with HoFH, sold under the name Juxtapid, and by the European Medicines Agency, where the brand name is Lojuxta.

The current trial involved more than 40 children and teenagers with HoFH aged 5-17 years; they were treated with the drug for 24 weeks, resulting in reductions of low density lipoprotein cholesterol of almost 54%, with nearly 42% reaching target levels.

The drug was also associated with marked reductions in other key lipids of at least 50%. However, 67% of patients also experienced gastrointestinal adverse events, and around 25% saw their levels of liver enzymes increase.
 

Early diagnosis ‘imperative’

The findings show that the “early diagnosis and treatment of HoFH is imperative,” said study presenter Luis Masana, MD, PhD, director of the Vascular Medicine and Metabolism Unit at Sant Joan de Reus University Hospital, Tarragona, Spain.

“I think that, with these results, we are bringing a new hope for this group of patients,” he continued. “I also think we will increase the quality of life, not just of the patients but also all the families involved in [managing] this problem.”

Session co-chair Andreas Zirlik, MD, PhD, head of the department of cardiology and chairman of the University Heart Center Graz, LKH-University Hospital, and Medical University of Graz (Austria), was more circumspect in his appraisal of the results.

He told this news organization that it is “always very difficult to establish therapy in pediatrics,” and believes that the drug “will give us an additional option” in managing HoFH.

However, Dr. Zirlik warned that he is a “little bit concerned” about lomitapide’s adverse event profile, and “would need to see a little bit deeper into the safety data.”

Highlighting the elevations in liver enzymes of around 25%, he asked: “What does it mean?” And how will it “play out in the long run?”

Beyond lomitapide, Dr. Zirlik pointed out that there are other drugs that have shown potential in managing HoFH and could potentially be used in the pediatric population, such as angiopoietin-like 3 protein (ANGPTL3) inhibitors and small interfering RNA (siRNA) compounds that target upstream production. “So, let’s see how they pan out,” he said.
 

Life-limiting condition

HoFH is an “ultra-rare, life-limiting condition,” with an estimated prevalence of approximately 3 per 1 million people, and a life expectancy in untreated patients of just 18 years, Dr. Masana said during his presentation.

Case series of lomitapide use in pediatric HoFH patients have shown encouraging results that are consistent with those seen in adults, he noted, with many able to achieve their LDL cholesterol target and stop or reduce apheresis.

To investigate further, a phase 3, single arm, open-label study was conducted. Following screening, 46 children and teenagers with HoFH underwent a 6- to 12-week run-in period, during which they were put on a low-fat diet with nutritional supplements.

“As you can imagine,” Dr. Masana said, “we are reducing the capacity for fat absorption with lomitapide, so the supplements and low-fat diet are necessary.”

Of these, 43 participants then entered a 24-week treatment period in which they were started on one of three doses, before undergoing dose escalation to the maximally tolerated dose. This was followed by an 80-week open-label safety phase, in which they continued on the maximally tolerated dose, then a follow-up period.

For the current presentation, Dr. Masana focused on the efficacy phase, showing that the mean age of participants was 10.7 years and that 55.8% were female. The HoFH diagnosis was confirmed genetically in 88.4% of cases.

Results showed that lomitapide was associated with a significant reduction in LDL cholesterol levels, from 435.8 mg/dL at baseline to 176.5 mg/dL at Week 24, which corresponded to a 53.5% overall reduction (P < .0001).

This meant that 41.9% of patients achieved their EAS LDL cholesterol target of less than 135 mg/dL at some point during the 24-week treatment period.

Stratifying by age, the reduction between baseline and week 24 was 538.5 mg/dL to 207.2 mg/dL, or 56.5%, in the 20 children aged 5-10 years, and 346.5 mg/dL to 149.9 mg/L, or 50.9%, in the 23 patients aged 11-17 years.

Dr. Masana explained that the results were “a little bit better in the younger group because they were receiving less treatment at this stage of the disease” than the older group.

He showed that lomitapide was associated with significant reductions in other lipid markers, including a 53.9% reduction in non–HDL cholesterol (P < .0001), a 50.1% drop in total cholesterol (P < .0001), and a 50.2% fall in very-low-density lipoprotein cholesterol (P < .0001).

Results showed 93% of patients experienced treatment-related adverse events, with 11.6% having serious events and 4.7% having events that led to study discontinuation. There was one (2.3%) major adverse cardiac event but no deaths.

He said that, despite these figures, the adverse events were “mostly mild or moderate.”

The majority (67%) of patients nevertheless had gastrointestinal adverse events, which were, “in general, associated with a lack of adherence to the low-fat diet.”

Aspartate aminotransferase levels were elevated in 23% of patients, while 28% had elevations in alanine aminotransferase, which were described by Dr. Masana as “moderate.”

The study was sponsored by Amryt Pharma. Dr. Masana declares relationships with Amarin, Amryt, Daiichi-Sankyo, Novartis, Sanofi, Servier, Servier, and Viatrix.

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

MANNHEIM, Germany – Lomitapide, which reduces lipoprotein production in the liver, could help manage pediatric homozygous familial hypercholesterolemia (HoFH), suggest results of a trial that showed large reductions in circulating lipids.

The research was presented May 23 at the 91st European Atherosclerosis Society Congress.

Lomitapide inhibits microsomal triglyceride transfer protein, which plays a key role in apolipoprotein B-containing lipoprotein assembly and secretion in the liver and intestines. Crucially, the drug acts independently of the LDL cholesterol receptor.

It was approved in December 2012 by the U.S. Food and Drug Administration for use in adults with HoFH, sold under the name Juxtapid, and by the European Medicines Agency, where the brand name is Lojuxta.

The current trial involved more than 40 children and teenagers with HoFH aged 5-17 years; they were treated with the drug for 24 weeks, resulting in reductions of low density lipoprotein cholesterol of almost 54%, with nearly 42% reaching target levels.

The drug was also associated with marked reductions in other key lipids of at least 50%. However, 67% of patients also experienced gastrointestinal adverse events, and around 25% saw their levels of liver enzymes increase.
 

Early diagnosis ‘imperative’

The findings show that the “early diagnosis and treatment of HoFH is imperative,” said study presenter Luis Masana, MD, PhD, director of the Vascular Medicine and Metabolism Unit at Sant Joan de Reus University Hospital, Tarragona, Spain.

“I think that, with these results, we are bringing a new hope for this group of patients,” he continued. “I also think we will increase the quality of life, not just of the patients but also all the families involved in [managing] this problem.”

Session co-chair Andreas Zirlik, MD, PhD, head of the department of cardiology and chairman of the University Heart Center Graz, LKH-University Hospital, and Medical University of Graz (Austria), was more circumspect in his appraisal of the results.

He told this news organization that it is “always very difficult to establish therapy in pediatrics,” and believes that the drug “will give us an additional option” in managing HoFH.

However, Dr. Zirlik warned that he is a “little bit concerned” about lomitapide’s adverse event profile, and “would need to see a little bit deeper into the safety data.”

Highlighting the elevations in liver enzymes of around 25%, he asked: “What does it mean?” And how will it “play out in the long run?”

Beyond lomitapide, Dr. Zirlik pointed out that there are other drugs that have shown potential in managing HoFH and could potentially be used in the pediatric population, such as angiopoietin-like 3 protein (ANGPTL3) inhibitors and small interfering RNA (siRNA) compounds that target upstream production. “So, let’s see how they pan out,” he said.
 

Life-limiting condition

HoFH is an “ultra-rare, life-limiting condition,” with an estimated prevalence of approximately 3 per 1 million people, and a life expectancy in untreated patients of just 18 years, Dr. Masana said during his presentation.

Case series of lomitapide use in pediatric HoFH patients have shown encouraging results that are consistent with those seen in adults, he noted, with many able to achieve their LDL cholesterol target and stop or reduce apheresis.

To investigate further, a phase 3, single arm, open-label study was conducted. Following screening, 46 children and teenagers with HoFH underwent a 6- to 12-week run-in period, during which they were put on a low-fat diet with nutritional supplements.

“As you can imagine,” Dr. Masana said, “we are reducing the capacity for fat absorption with lomitapide, so the supplements and low-fat diet are necessary.”

Of these, 43 participants then entered a 24-week treatment period in which they were started on one of three doses, before undergoing dose escalation to the maximally tolerated dose. This was followed by an 80-week open-label safety phase, in which they continued on the maximally tolerated dose, then a follow-up period.

For the current presentation, Dr. Masana focused on the efficacy phase, showing that the mean age of participants was 10.7 years and that 55.8% were female. The HoFH diagnosis was confirmed genetically in 88.4% of cases.

Results showed that lomitapide was associated with a significant reduction in LDL cholesterol levels, from 435.8 mg/dL at baseline to 176.5 mg/dL at Week 24, which corresponded to a 53.5% overall reduction (P < .0001).

This meant that 41.9% of patients achieved their EAS LDL cholesterol target of less than 135 mg/dL at some point during the 24-week treatment period.

Stratifying by age, the reduction between baseline and week 24 was 538.5 mg/dL to 207.2 mg/dL, or 56.5%, in the 20 children aged 5-10 years, and 346.5 mg/dL to 149.9 mg/L, or 50.9%, in the 23 patients aged 11-17 years.

Dr. Masana explained that the results were “a little bit better in the younger group because they were receiving less treatment at this stage of the disease” than the older group.

He showed that lomitapide was associated with significant reductions in other lipid markers, including a 53.9% reduction in non–HDL cholesterol (P < .0001), a 50.1% drop in total cholesterol (P < .0001), and a 50.2% fall in very-low-density lipoprotein cholesterol (P < .0001).

Results showed 93% of patients experienced treatment-related adverse events, with 11.6% having serious events and 4.7% having events that led to study discontinuation. There was one (2.3%) major adverse cardiac event but no deaths.

He said that, despite these figures, the adverse events were “mostly mild or moderate.”

The majority (67%) of patients nevertheless had gastrointestinal adverse events, which were, “in general, associated with a lack of adherence to the low-fat diet.”

Aspartate aminotransferase levels were elevated in 23% of patients, while 28% had elevations in alanine aminotransferase, which were described by Dr. Masana as “moderate.”

The study was sponsored by Amryt Pharma. Dr. Masana declares relationships with Amarin, Amryt, Daiichi-Sankyo, Novartis, Sanofi, Servier, Servier, and Viatrix.

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

MANNHEIM, Germany – Lomitapide, which reduces lipoprotein production in the liver, could help manage pediatric homozygous familial hypercholesterolemia (HoFH), suggest results of a trial that showed large reductions in circulating lipids.

The research was presented May 23 at the 91st European Atherosclerosis Society Congress.

Lomitapide inhibits microsomal triglyceride transfer protein, which plays a key role in apolipoprotein B-containing lipoprotein assembly and secretion in the liver and intestines. Crucially, the drug acts independently of the LDL cholesterol receptor.

It was approved in December 2012 by the U.S. Food and Drug Administration for use in adults with HoFH, sold under the name Juxtapid, and by the European Medicines Agency, where the brand name is Lojuxta.

The current trial involved more than 40 children and teenagers with HoFH aged 5-17 years; they were treated with the drug for 24 weeks, resulting in reductions of low density lipoprotein cholesterol of almost 54%, with nearly 42% reaching target levels.

The drug was also associated with marked reductions in other key lipids of at least 50%. However, 67% of patients also experienced gastrointestinal adverse events, and around 25% saw their levels of liver enzymes increase.
 

Early diagnosis ‘imperative’

The findings show that the “early diagnosis and treatment of HoFH is imperative,” said study presenter Luis Masana, MD, PhD, director of the Vascular Medicine and Metabolism Unit at Sant Joan de Reus University Hospital, Tarragona, Spain.

“I think that, with these results, we are bringing a new hope for this group of patients,” he continued. “I also think we will increase the quality of life, not just of the patients but also all the families involved in [managing] this problem.”

Session co-chair Andreas Zirlik, MD, PhD, head of the department of cardiology and chairman of the University Heart Center Graz, LKH-University Hospital, and Medical University of Graz (Austria), was more circumspect in his appraisal of the results.

He told this news organization that it is “always very difficult to establish therapy in pediatrics,” and believes that the drug “will give us an additional option” in managing HoFH.

However, Dr. Zirlik warned that he is a “little bit concerned” about lomitapide’s adverse event profile, and “would need to see a little bit deeper into the safety data.”

Highlighting the elevations in liver enzymes of around 25%, he asked: “What does it mean?” And how will it “play out in the long run?”

Beyond lomitapide, Dr. Zirlik pointed out that there are other drugs that have shown potential in managing HoFH and could potentially be used in the pediatric population, such as angiopoietin-like 3 protein (ANGPTL3) inhibitors and small interfering RNA (siRNA) compounds that target upstream production. “So, let’s see how they pan out,” he said.
 

Life-limiting condition

HoFH is an “ultra-rare, life-limiting condition,” with an estimated prevalence of approximately 3 per 1 million people, and a life expectancy in untreated patients of just 18 years, Dr. Masana said during his presentation.

Case series of lomitapide use in pediatric HoFH patients have shown encouraging results that are consistent with those seen in adults, he noted, with many able to achieve their LDL cholesterol target and stop or reduce apheresis.

To investigate further, a phase 3, single arm, open-label study was conducted. Following screening, 46 children and teenagers with HoFH underwent a 6- to 12-week run-in period, during which they were put on a low-fat diet with nutritional supplements.

“As you can imagine,” Dr. Masana said, “we are reducing the capacity for fat absorption with lomitapide, so the supplements and low-fat diet are necessary.”

Of these, 43 participants then entered a 24-week treatment period in which they were started on one of three doses, before undergoing dose escalation to the maximally tolerated dose. This was followed by an 80-week open-label safety phase, in which they continued on the maximally tolerated dose, then a follow-up period.

For the current presentation, Dr. Masana focused on the efficacy phase, showing that the mean age of participants was 10.7 years and that 55.8% were female. The HoFH diagnosis was confirmed genetically in 88.4% of cases.

Results showed that lomitapide was associated with a significant reduction in LDL cholesterol levels, from 435.8 mg/dL at baseline to 176.5 mg/dL at Week 24, which corresponded to a 53.5% overall reduction (P < .0001).

This meant that 41.9% of patients achieved their EAS LDL cholesterol target of less than 135 mg/dL at some point during the 24-week treatment period.

Stratifying by age, the reduction between baseline and week 24 was 538.5 mg/dL to 207.2 mg/dL, or 56.5%, in the 20 children aged 5-10 years, and 346.5 mg/dL to 149.9 mg/L, or 50.9%, in the 23 patients aged 11-17 years.

Dr. Masana explained that the results were “a little bit better in the younger group because they were receiving less treatment at this stage of the disease” than the older group.

He showed that lomitapide was associated with significant reductions in other lipid markers, including a 53.9% reduction in non–HDL cholesterol (P < .0001), a 50.1% drop in total cholesterol (P < .0001), and a 50.2% fall in very-low-density lipoprotein cholesterol (P < .0001).

Results showed 93% of patients experienced treatment-related adverse events, with 11.6% having serious events and 4.7% having events that led to study discontinuation. There was one (2.3%) major adverse cardiac event but no deaths.

He said that, despite these figures, the adverse events were “mostly mild or moderate.”

The majority (67%) of patients nevertheless had gastrointestinal adverse events, which were, “in general, associated with a lack of adherence to the low-fat diet.”

Aspartate aminotransferase levels were elevated in 23% of patients, while 28% had elevations in alanine aminotransferase, which were described by Dr. Masana as “moderate.”

The study was sponsored by Amryt Pharma. Dr. Masana declares relationships with Amarin, Amryt, Daiichi-Sankyo, Novartis, Sanofi, Servier, Servier, and Viatrix.

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

The prophylactic use of antiemetic, antipyretic, or antibiotic drugs in older patients with acute stroke did not reduce the risk of poor functional outcome in the PRECIOUS trial.

“The results of PRECIOUS do not support preventive use of antiemetic, antipyretic, or antibiotic drugs in older patients with acute stroke,” senior study author Bart van der Worp, MD, professor of acute neurology at University Medical Center, Utrecht, the Netherlands, concluded.

“This trial was all about prevention,” trial co-investigator, Philip Bath, MD, professor of stroke medicine at the University of Nottingham (England), said in an interview.

“It was trying to improve outcomes by preventing infection, fever, and aspiration pneumonia, but the message from these results is that while we should be on the lookout for these complications and treat them early when they occur, we don’t need to give these medications on a prophylactic basis.”

The PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke (PRECIOUS) trial was presented at the annual European Stroke Organisation Conference, held in Munich.

Dr. Van der Worp explained that infections, fever, and aspiration pneumonia frequently occur following stroke, particularly in older patients, and these poststroke complications are associated with an increased risk of death and poor functional outcome.

“We assessed whether a pharmacological strategy to reduce the risk of infections and fever improves outcomes of elderly patients with moderately severe or severe stroke,” he said.

Previous studies looking at this approach have been performed in broad populations of stroke patients who had a relatively low risk of poststroke complications, thereby reducing the potential for benefit from these interventions. 

The current PRECIOUS trial was therefore conducted in a more selective elderly population with more severe strokes, a group believed to be at higher risk of infection and fever.  

The trial included patients aged 66 years or older with moderately severe to severe ischemic stroke (National Institutes of Health Stroke Scale score ≥ 6) or intracerebral hemorrhage.

They were randomized in a 3 x 2 factorial design to oral, rectal, or intravenous metoclopramide (10 mg three times a day); intravenous ceftriaxone (2,000 mg once daily); oral, rectal, or intravenous paracetamol (1,000 mg four times daily); or usual care.

Medications were started within 24 hours after symptom onset and continued for 4 days or until complete recovery or discharge from hospital, if earlier.

“We assessed these three simple, safe, and inexpensive therapies – paracetamol to prevent fever; the antiemetic, metoclopramide, to prevent aspiration; and ceftriaxone, which is the preferred antibiotic for post-stroke pneumonia in the Netherlands,” Dr. van der Worp said.

The primary outcome was modified Rankin Scale (mRS) score at 90 days.

The trial was aiming to enroll 3,800 patients from 67 European sites but was stopped after 1,493 patients had been included because of lack of funding. After excluding patients who withdrew consent or were lost to follow-up, 1,471 patients were included in the intention-to-treat analysis.

Results showed no effect on the primary outcome of any of the prophylactic treatments.

“None of the medications had any effect on the functional outcome at 90 days. This was a surprise to me,” Dr. Van der Worp commented. “I had expected that at least one of the medications would have been of benefit.”

A secondary outcome was the diagnosis of pneumonia, which again was not reduced by any of the medications.

“Remarkably, neither ceftriaxone nor metoclopramide had any effect on the risk of developing pneumonia. It was all quite disappointing,” van der Worp said.

There was, however, a reduction in the incidence of urinary tract infections in the ceftriaxone group.

Trying to explain why there was a reduction in urinary tract infections but not pneumonia with the antibiotic, Dr. Van der Worp pointed out that poststroke pneumonia is to a large extent caused by a mechanical process (aspiration), and bacteria may only play a minor role in its development. 

He said he was therefore surprised that metoclopramide, which should prevent the mechanical process of aspiration, did not reduce the development of pneumonia.

He suggested that some patients may have already experienced aspiration before the metoclopramide was started, noting that many patients with acute stroke already have signs of pneumonia on CT scan in the first few hours after symptom onset.

A previous smaller study (MAPS) had shown a lower rate of pneumonia in stroke patients given metoclopramide, but in this study the drug was given for 3 weeks.

Discussing the PRECIOUS trial at the ESOC meeting, Christine Roffe, MD, professor of stroke medicine at Keele (England) University, and senior investigator of the MAPS study, suggested that a longer period of metoclopramide treatment may be needed than the 4 days given in the PRECIOUS study, as the risk of pneumonia persists for longer than just a few days.  

She noted that another trial (MAPS-2) is now underway in the United Kingdom to try and confirm the first MAPS result with longer duration metoclopramide.  

Dr. Van der Worp responded: “Certainly, I think that the MAPS-2 study should be continued. It is investigating a much longer duration of treatment, which may be beneficial, especially in patients with more severe strokes.” 

On the reason for the disappointing results with paracetamol, Dr. Van der Worp elaborated: “We found that only a very few of these older patients developed a fever – only about 5% in the control group. Paracetamol did reduce the risk of fever, but because the proportion of patients who developed fever was so small, this may have been why it didn’t translate into any effect on the functional outcome.” 

Dr. Roffe concluded that PRECIOUS was an important study. “There is also a positive message here. We have all been worried about using too many antibiotics. We need to make sure we use these drugs responsibly. I think this trial has told us there is little point in using antibiotics in a preventative way in these patients.”

She added that although the trial was stopped prematurely, it had produced decisive results.

“Yes, I believe that even if the trial was much larger, we still would not have shown an effect,” Dr. Van der Worp agreed.

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

The prophylactic use of antiemetic, antipyretic, or antibiotic drugs in older patients with acute stroke did not reduce the risk of poor functional outcome in the PRECIOUS trial.

“The results of PRECIOUS do not support preventive use of antiemetic, antipyretic, or antibiotic drugs in older patients with acute stroke,” senior study author Bart van der Worp, MD, professor of acute neurology at University Medical Center, Utrecht, the Netherlands, concluded.

“This trial was all about prevention,” trial co-investigator, Philip Bath, MD, professor of stroke medicine at the University of Nottingham (England), said in an interview.

“It was trying to improve outcomes by preventing infection, fever, and aspiration pneumonia, but the message from these results is that while we should be on the lookout for these complications and treat them early when they occur, we don’t need to give these medications on a prophylactic basis.”

The PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke (PRECIOUS) trial was presented at the annual European Stroke Organisation Conference, held in Munich.

Dr. Van der Worp explained that infections, fever, and aspiration pneumonia frequently occur following stroke, particularly in older patients, and these poststroke complications are associated with an increased risk of death and poor functional outcome.

“We assessed whether a pharmacological strategy to reduce the risk of infections and fever improves outcomes of elderly patients with moderately severe or severe stroke,” he said.

Previous studies looking at this approach have been performed in broad populations of stroke patients who had a relatively low risk of poststroke complications, thereby reducing the potential for benefit from these interventions. 

The current PRECIOUS trial was therefore conducted in a more selective elderly population with more severe strokes, a group believed to be at higher risk of infection and fever.  

The trial included patients aged 66 years or older with moderately severe to severe ischemic stroke (National Institutes of Health Stroke Scale score ≥ 6) or intracerebral hemorrhage.

They were randomized in a 3 x 2 factorial design to oral, rectal, or intravenous metoclopramide (10 mg three times a day); intravenous ceftriaxone (2,000 mg once daily); oral, rectal, or intravenous paracetamol (1,000 mg four times daily); or usual care.

Medications were started within 24 hours after symptom onset and continued for 4 days or until complete recovery or discharge from hospital, if earlier.

“We assessed these three simple, safe, and inexpensive therapies – paracetamol to prevent fever; the antiemetic, metoclopramide, to prevent aspiration; and ceftriaxone, which is the preferred antibiotic for post-stroke pneumonia in the Netherlands,” Dr. van der Worp said.

The primary outcome was modified Rankin Scale (mRS) score at 90 days.

The trial was aiming to enroll 3,800 patients from 67 European sites but was stopped after 1,493 patients had been included because of lack of funding. After excluding patients who withdrew consent or were lost to follow-up, 1,471 patients were included in the intention-to-treat analysis.

Results showed no effect on the primary outcome of any of the prophylactic treatments.

“None of the medications had any effect on the functional outcome at 90 days. This was a surprise to me,” Dr. Van der Worp commented. “I had expected that at least one of the medications would have been of benefit.”

A secondary outcome was the diagnosis of pneumonia, which again was not reduced by any of the medications.

“Remarkably, neither ceftriaxone nor metoclopramide had any effect on the risk of developing pneumonia. It was all quite disappointing,” van der Worp said.

There was, however, a reduction in the incidence of urinary tract infections in the ceftriaxone group.

Trying to explain why there was a reduction in urinary tract infections but not pneumonia with the antibiotic, Dr. Van der Worp pointed out that poststroke pneumonia is to a large extent caused by a mechanical process (aspiration), and bacteria may only play a minor role in its development. 

He said he was therefore surprised that metoclopramide, which should prevent the mechanical process of aspiration, did not reduce the development of pneumonia.

He suggested that some patients may have already experienced aspiration before the metoclopramide was started, noting that many patients with acute stroke already have signs of pneumonia on CT scan in the first few hours after symptom onset.

A previous smaller study (MAPS) had shown a lower rate of pneumonia in stroke patients given metoclopramide, but in this study the drug was given for 3 weeks.

Discussing the PRECIOUS trial at the ESOC meeting, Christine Roffe, MD, professor of stroke medicine at Keele (England) University, and senior investigator of the MAPS study, suggested that a longer period of metoclopramide treatment may be needed than the 4 days given in the PRECIOUS study, as the risk of pneumonia persists for longer than just a few days.  

She noted that another trial (MAPS-2) is now underway in the United Kingdom to try and confirm the first MAPS result with longer duration metoclopramide.  

Dr. Van der Worp responded: “Certainly, I think that the MAPS-2 study should be continued. It is investigating a much longer duration of treatment, which may be beneficial, especially in patients with more severe strokes.” 

On the reason for the disappointing results with paracetamol, Dr. Van der Worp elaborated: “We found that only a very few of these older patients developed a fever – only about 5% in the control group. Paracetamol did reduce the risk of fever, but because the proportion of patients who developed fever was so small, this may have been why it didn’t translate into any effect on the functional outcome.” 

Dr. Roffe concluded that PRECIOUS was an important study. “There is also a positive message here. We have all been worried about using too many antibiotics. We need to make sure we use these drugs responsibly. I think this trial has told us there is little point in using antibiotics in a preventative way in these patients.”

She added that although the trial was stopped prematurely, it had produced decisive results.

“Yes, I believe that even if the trial was much larger, we still would not have shown an effect,” Dr. Van der Worp agreed.

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

The prophylactic use of antiemetic, antipyretic, or antibiotic drugs in older patients with acute stroke did not reduce the risk of poor functional outcome in the PRECIOUS trial.

“The results of PRECIOUS do not support preventive use of antiemetic, antipyretic, or antibiotic drugs in older patients with acute stroke,” senior study author Bart van der Worp, MD, professor of acute neurology at University Medical Center, Utrecht, the Netherlands, concluded.

“This trial was all about prevention,” trial co-investigator, Philip Bath, MD, professor of stroke medicine at the University of Nottingham (England), said in an interview.

“It was trying to improve outcomes by preventing infection, fever, and aspiration pneumonia, but the message from these results is that while we should be on the lookout for these complications and treat them early when they occur, we don’t need to give these medications on a prophylactic basis.”

The PREvention of Complications to Improve OUtcome in elderly patients with acute Stroke (PRECIOUS) trial was presented at the annual European Stroke Organisation Conference, held in Munich.

Dr. Van der Worp explained that infections, fever, and aspiration pneumonia frequently occur following stroke, particularly in older patients, and these poststroke complications are associated with an increased risk of death and poor functional outcome.

“We assessed whether a pharmacological strategy to reduce the risk of infections and fever improves outcomes of elderly patients with moderately severe or severe stroke,” he said.

Previous studies looking at this approach have been performed in broad populations of stroke patients who had a relatively low risk of poststroke complications, thereby reducing the potential for benefit from these interventions. 

The current PRECIOUS trial was therefore conducted in a more selective elderly population with more severe strokes, a group believed to be at higher risk of infection and fever.  

The trial included patients aged 66 years or older with moderately severe to severe ischemic stroke (National Institutes of Health Stroke Scale score ≥ 6) or intracerebral hemorrhage.

They were randomized in a 3 x 2 factorial design to oral, rectal, or intravenous metoclopramide (10 mg three times a day); intravenous ceftriaxone (2,000 mg once daily); oral, rectal, or intravenous paracetamol (1,000 mg four times daily); or usual care.

Medications were started within 24 hours after symptom onset and continued for 4 days or until complete recovery or discharge from hospital, if earlier.

“We assessed these three simple, safe, and inexpensive therapies – paracetamol to prevent fever; the antiemetic, metoclopramide, to prevent aspiration; and ceftriaxone, which is the preferred antibiotic for post-stroke pneumonia in the Netherlands,” Dr. van der Worp said.

The primary outcome was modified Rankin Scale (mRS) score at 90 days.

The trial was aiming to enroll 3,800 patients from 67 European sites but was stopped after 1,493 patients had been included because of lack of funding. After excluding patients who withdrew consent or were lost to follow-up, 1,471 patients were included in the intention-to-treat analysis.

Results showed no effect on the primary outcome of any of the prophylactic treatments.

“None of the medications had any effect on the functional outcome at 90 days. This was a surprise to me,” Dr. Van der Worp commented. “I had expected that at least one of the medications would have been of benefit.”

A secondary outcome was the diagnosis of pneumonia, which again was not reduced by any of the medications.

“Remarkably, neither ceftriaxone nor metoclopramide had any effect on the risk of developing pneumonia. It was all quite disappointing,” van der Worp said.

There was, however, a reduction in the incidence of urinary tract infections in the ceftriaxone group.

Trying to explain why there was a reduction in urinary tract infections but not pneumonia with the antibiotic, Dr. Van der Worp pointed out that poststroke pneumonia is to a large extent caused by a mechanical process (aspiration), and bacteria may only play a minor role in its development. 

He said he was therefore surprised that metoclopramide, which should prevent the mechanical process of aspiration, did not reduce the development of pneumonia.

He suggested that some patients may have already experienced aspiration before the metoclopramide was started, noting that many patients with acute stroke already have signs of pneumonia on CT scan in the first few hours after symptom onset.

A previous smaller study (MAPS) had shown a lower rate of pneumonia in stroke patients given metoclopramide, but in this study the drug was given for 3 weeks.

Discussing the PRECIOUS trial at the ESOC meeting, Christine Roffe, MD, professor of stroke medicine at Keele (England) University, and senior investigator of the MAPS study, suggested that a longer period of metoclopramide treatment may be needed than the 4 days given in the PRECIOUS study, as the risk of pneumonia persists for longer than just a few days.  

She noted that another trial (MAPS-2) is now underway in the United Kingdom to try and confirm the first MAPS result with longer duration metoclopramide.  

Dr. Van der Worp responded: “Certainly, I think that the MAPS-2 study should be continued. It is investigating a much longer duration of treatment, which may be beneficial, especially in patients with more severe strokes.” 

On the reason for the disappointing results with paracetamol, Dr. Van der Worp elaborated: “We found that only a very few of these older patients developed a fever – only about 5% in the control group. Paracetamol did reduce the risk of fever, but because the proportion of patients who developed fever was so small, this may have been why it didn’t translate into any effect on the functional outcome.” 

Dr. Roffe concluded that PRECIOUS was an important study. “There is also a positive message here. We have all been worried about using too many antibiotics. We need to make sure we use these drugs responsibly. I think this trial has told us there is little point in using antibiotics in a preventative way in these patients.”

She added that although the trial was stopped prematurely, it had produced decisive results.

“Yes, I believe that even if the trial was much larger, we still would not have shown an effect,” Dr. Van der Worp agreed.

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

MUNICH, GERMANY – Intensive systolic blood pressure (SBP) management in the 24 hours after successful recanalization with intra-arterial thrombectomy (IAT) substantially increases the risk of a poor outcome at 3 months, suggests results from the OPTIMAL-BP trial.

The research, presented at the annual European Stroke Organisation Conference, supports the latest U.S. and European guidelines, which recommend a relatively high upper SBP limit.

For the trial, which was halted early, more than 300 patients who successfully underwent IAT for acute ischemic stroke were randomly assigned to intensive or conventional BP management within 2 hours of recanalization.

Patients in the intensive group were 44% less likely than those assigned to conventional management to have a favorable outcome of a modified Rankin Scale (mRS) score of 0-2 at 3 months, while having similar rates of adverse outcomes.

The results suggest that intensive BP lowering in the 24 hours after recanalization leads to an increased risk of disability without decreasing the risk of intracerebral hemorrhage (ICH) or death, said study presenter Hyo Suk Nam, MD, PhD, department of neurology, Yonsei (South Korea) University.

Consequently, the trial “does not support intensive blood pressure management” in that early post-IAT period, although the “optimal blood pressure range remains unclear and requires more investigation,” he said.

Dr. Nam added that the results suggest, “despite recanalization, some areas in the ischemic brain may have already been damaged,” or that surrounding areas continue to have reduced blood circulation.

He believes that these areas may have reduced capacity for autoregulation and so “may not effectively counteract sudden drops in blood pressure.

“Thus, intensive blood pressure lowering may further reduce blood flow ... and exacerbate ischemic injury.”

On the other hand, the conventional group confirmed prior studies indicating that high SBP is associated with poor outcomes.

Dr. Nam suggested that increased BP “may be a physiological response to the acute stress of stroke,” but that the adverse outcomes in some patients “might reflect stroke severity rather than being a direct effect of raised blood pressure.”

Session cochair Carlos Molina, MD, director of the stroke unit and brain hemodynamics at Vall d’Hebron Hospital, Barcelona, commented that “it’s very important to remember that the guidances are endorsed by the results of this study.

He said in an interview that “intensive blood pressure lowering harms the brain, especially just after reperfusion.

“So, the results are in line with the previous concept that we need to be careful, as intensive blood pressure lowering is associated with clinical deterioration and poor outcomes.”

He agreed with Dr. Nam that, with high BP also being harmful, the optimal range is currently unclear.

Dr. Molina underlined, however, that, in the absence of further studies, “we have to stick to the guidelines.”

Dr. Nam pointed out that, while high BP can result in reperfusion injury or ICH, “too low blood pressure can worsen cerebral ischemia.”

Yet the management of BP after successful recanalization with IAT is “largely unknown.”

He noted that, while both the European Stroke Organisation and American Heart Association/American Stroke Association guidelines recommend that BP should be kept below 180/105 mm Hg in patients who have undergone successful recanalization, the evidence class for this recommendation is “weak.”

Furthermore, observational studies have indicated that higher maximum or average SBP is associated with poor outcomes, but two multicenter clinical trials of intensive BP lowering after IAT, BP-TARGET and ENCHANTED2/MT, had conflicting results.

The researchers therefore investigated whether intensive BP management would result in better clinical outcomes in the 24 hours after successful recanalization with IAT.

They conducted a multicenter, open-label trial in which patients aged 20 years and older who underwent IAT for acute ischemic stroke with large cerebrovascular occlusion and had an SBP of at least 140 mm Hg were recruited from 19 centers in South Korea between June 2020 and November 2022.

The patients were randomly assigned within 2 hours of successful recanalization to intensive BP management, targeting an SBP less than 140 mm Hg, or conventional management, targeting an SBP of 140-180 mm Hg.

Clinicians could use local treatment protocols based on available intravenous BP-lowering drugs. BP was measured every 15 minutes for the first hour after randomization and then hourly for 24 hours.

The trial was terminated early because of safety concerns after the ENCHANTED2/MT trial revealed a negative impact on mRS scores at 3 months with intensive BP management.

Of 1,606 potentially eligible patients with acute ischemic stroke treated with IAT, 306 were randomly assigned, with 155 in the intensive group and 150 in the conventional group included in the primary analysis.

The mean age was 73.1 years, and 40.3% were women. The average National Institutes of Health Stroke Scale (NIHSS) score prior to IAT was 13. The mean time from stroke onset to randomization was 480 minutes (interquartile range, 320-820 minutes).

At 24 hours, the mean SBP in the intensive group was 129.2 mm Hg versus 138.0 mm Hg in the conventional group, for a between-group difference of 9.6 mm Hg (95% confidence interval, –12.2 to –6.9, P < .001).

Patients in the intensive group spent 80.3% of the first 24 hours with SBP less than 140 mm Hg versus 54.2% in the conventional group (P < .001). In contrast, conventional group patients spent 42.1% of the first 24 hours with SBP 140-180 mm Hg versus 14.2% in the intensive group.

Crucially, Dr. Nam showed that patients in the intensive BP-lowering group were significantly less likely than those in the conventional group to have a favorable outcome, defined as an mRS score of 0-2, at 3 months, at 39.4% versus 54.4%, or an adjusted odds ratio of 0.56 (95% CI, 0.33-0.96, P = .034).

Moreover, a poor outcome was 1.84 (95% CI, 1.17-2.91) times more common in the intervention group than the conventional group, Dr. Nam reported, with a number needed to harm of 6.6.

In terms of safety, there was no significant difference in rates of symptomatic ICH between the groups, at 9% in the intensive versus 8.1% in the conventional groups, or an aOR of 1.10 (95% CI, 0.48-2.53, P = .816).

There was also no difference in the rate of death related to the index stroke within 90 days, at 7.7% versus 5.4% (AOR, 1.73; 95% CI, 0.61-4.92, P = .307).

There were also no significant differences between the groups in key secondary outcomes, such as NIHSS score at 24 hours, recanalization at 24 hours, favorable outcome on the mRS at 1 month, and the EQ-5D-3L quality of life score.

However, patients in the intensive group were substantially more likely to experience malignant brain edema, at 7.7% versus 1.3% in the conventional group (aOR, 7.88; 95% CI, 1.57-39.39, P = .012).

Restricted cubic spline regression analysis indicated that there was a U-shaped relationship between mean SBP during the 24 hours following IAT and the odds ratio of a poor outcome, in which both a low and a high BPe were unfavorable.

Dr. Nam cautioned that, when interpreting the results, the early termination of the study may have reduced its statistical power and increased the likelihood of random and exaggerated treatment effects.

He also noted that the study was conducted in South Korea, and so the results may not be generalizable to other populations.

The study received a grant from the Patient-Centered Clinical Research Coordinating Center, funded by the Ministry of Health and Welfare. No relevant financial relationships were declared.

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

MUNICH, GERMANY – Intensive systolic blood pressure (SBP) management in the 24 hours after successful recanalization with intra-arterial thrombectomy (IAT) substantially increases the risk of a poor outcome at 3 months, suggests results from the OPTIMAL-BP trial.

The research, presented at the annual European Stroke Organisation Conference, supports the latest U.S. and European guidelines, which recommend a relatively high upper SBP limit.

For the trial, which was halted early, more than 300 patients who successfully underwent IAT for acute ischemic stroke were randomly assigned to intensive or conventional BP management within 2 hours of recanalization.

Patients in the intensive group were 44% less likely than those assigned to conventional management to have a favorable outcome of a modified Rankin Scale (mRS) score of 0-2 at 3 months, while having similar rates of adverse outcomes.

The results suggest that intensive BP lowering in the 24 hours after recanalization leads to an increased risk of disability without decreasing the risk of intracerebral hemorrhage (ICH) or death, said study presenter Hyo Suk Nam, MD, PhD, department of neurology, Yonsei (South Korea) University.

Consequently, the trial “does not support intensive blood pressure management” in that early post-IAT period, although the “optimal blood pressure range remains unclear and requires more investigation,” he said.

Dr. Nam added that the results suggest, “despite recanalization, some areas in the ischemic brain may have already been damaged,” or that surrounding areas continue to have reduced blood circulation.

He believes that these areas may have reduced capacity for autoregulation and so “may not effectively counteract sudden drops in blood pressure.

“Thus, intensive blood pressure lowering may further reduce blood flow ... and exacerbate ischemic injury.”

On the other hand, the conventional group confirmed prior studies indicating that high SBP is associated with poor outcomes.

Dr. Nam suggested that increased BP “may be a physiological response to the acute stress of stroke,” but that the adverse outcomes in some patients “might reflect stroke severity rather than being a direct effect of raised blood pressure.”

Session cochair Carlos Molina, MD, director of the stroke unit and brain hemodynamics at Vall d’Hebron Hospital, Barcelona, commented that “it’s very important to remember that the guidances are endorsed by the results of this study.

He said in an interview that “intensive blood pressure lowering harms the brain, especially just after reperfusion.

“So, the results are in line with the previous concept that we need to be careful, as intensive blood pressure lowering is associated with clinical deterioration and poor outcomes.”

He agreed with Dr. Nam that, with high BP also being harmful, the optimal range is currently unclear.

Dr. Molina underlined, however, that, in the absence of further studies, “we have to stick to the guidelines.”

Dr. Nam pointed out that, while high BP can result in reperfusion injury or ICH, “too low blood pressure can worsen cerebral ischemia.”

Yet the management of BP after successful recanalization with IAT is “largely unknown.”

He noted that, while both the European Stroke Organisation and American Heart Association/American Stroke Association guidelines recommend that BP should be kept below 180/105 mm Hg in patients who have undergone successful recanalization, the evidence class for this recommendation is “weak.”

Furthermore, observational studies have indicated that higher maximum or average SBP is associated with poor outcomes, but two multicenter clinical trials of intensive BP lowering after IAT, BP-TARGET and ENCHANTED2/MT, had conflicting results.

The researchers therefore investigated whether intensive BP management would result in better clinical outcomes in the 24 hours after successful recanalization with IAT.

They conducted a multicenter, open-label trial in which patients aged 20 years and older who underwent IAT for acute ischemic stroke with large cerebrovascular occlusion and had an SBP of at least 140 mm Hg were recruited from 19 centers in South Korea between June 2020 and November 2022.

The patients were randomly assigned within 2 hours of successful recanalization to intensive BP management, targeting an SBP less than 140 mm Hg, or conventional management, targeting an SBP of 140-180 mm Hg.

Clinicians could use local treatment protocols based on available intravenous BP-lowering drugs. BP was measured every 15 minutes for the first hour after randomization and then hourly for 24 hours.

The trial was terminated early because of safety concerns after the ENCHANTED2/MT trial revealed a negative impact on mRS scores at 3 months with intensive BP management.

Of 1,606 potentially eligible patients with acute ischemic stroke treated with IAT, 306 were randomly assigned, with 155 in the intensive group and 150 in the conventional group included in the primary analysis.

The mean age was 73.1 years, and 40.3% were women. The average National Institutes of Health Stroke Scale (NIHSS) score prior to IAT was 13. The mean time from stroke onset to randomization was 480 minutes (interquartile range, 320-820 minutes).

At 24 hours, the mean SBP in the intensive group was 129.2 mm Hg versus 138.0 mm Hg in the conventional group, for a between-group difference of 9.6 mm Hg (95% confidence interval, –12.2 to –6.9, P < .001).

Patients in the intensive group spent 80.3% of the first 24 hours with SBP less than 140 mm Hg versus 54.2% in the conventional group (P < .001). In contrast, conventional group patients spent 42.1% of the first 24 hours with SBP 140-180 mm Hg versus 14.2% in the intensive group.

Crucially, Dr. Nam showed that patients in the intensive BP-lowering group were significantly less likely than those in the conventional group to have a favorable outcome, defined as an mRS score of 0-2, at 3 months, at 39.4% versus 54.4%, or an adjusted odds ratio of 0.56 (95% CI, 0.33-0.96, P = .034).

Moreover, a poor outcome was 1.84 (95% CI, 1.17-2.91) times more common in the intervention group than the conventional group, Dr. Nam reported, with a number needed to harm of 6.6.

In terms of safety, there was no significant difference in rates of symptomatic ICH between the groups, at 9% in the intensive versus 8.1% in the conventional groups, or an aOR of 1.10 (95% CI, 0.48-2.53, P = .816).

There was also no difference in the rate of death related to the index stroke within 90 days, at 7.7% versus 5.4% (AOR, 1.73; 95% CI, 0.61-4.92, P = .307).

There were also no significant differences between the groups in key secondary outcomes, such as NIHSS score at 24 hours, recanalization at 24 hours, favorable outcome on the mRS at 1 month, and the EQ-5D-3L quality of life score.

However, patients in the intensive group were substantially more likely to experience malignant brain edema, at 7.7% versus 1.3% in the conventional group (aOR, 7.88; 95% CI, 1.57-39.39, P = .012).

Restricted cubic spline regression analysis indicated that there was a U-shaped relationship between mean SBP during the 24 hours following IAT and the odds ratio of a poor outcome, in which both a low and a high BPe were unfavorable.

Dr. Nam cautioned that, when interpreting the results, the early termination of the study may have reduced its statistical power and increased the likelihood of random and exaggerated treatment effects.

He also noted that the study was conducted in South Korea, and so the results may not be generalizable to other populations.

The study received a grant from the Patient-Centered Clinical Research Coordinating Center, funded by the Ministry of Health and Welfare. No relevant financial relationships were declared.

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

MUNICH, GERMANY – Intensive systolic blood pressure (SBP) management in the 24 hours after successful recanalization with intra-arterial thrombectomy (IAT) substantially increases the risk of a poor outcome at 3 months, suggests results from the OPTIMAL-BP trial.

The research, presented at the annual European Stroke Organisation Conference, supports the latest U.S. and European guidelines, which recommend a relatively high upper SBP limit.

For the trial, which was halted early, more than 300 patients who successfully underwent IAT for acute ischemic stroke were randomly assigned to intensive or conventional BP management within 2 hours of recanalization.

Patients in the intensive group were 44% less likely than those assigned to conventional management to have a favorable outcome of a modified Rankin Scale (mRS) score of 0-2 at 3 months, while having similar rates of adverse outcomes.

The results suggest that intensive BP lowering in the 24 hours after recanalization leads to an increased risk of disability without decreasing the risk of intracerebral hemorrhage (ICH) or death, said study presenter Hyo Suk Nam, MD, PhD, department of neurology, Yonsei (South Korea) University.

Consequently, the trial “does not support intensive blood pressure management” in that early post-IAT period, although the “optimal blood pressure range remains unclear and requires more investigation,” he said.

Dr. Nam added that the results suggest, “despite recanalization, some areas in the ischemic brain may have already been damaged,” or that surrounding areas continue to have reduced blood circulation.

He believes that these areas may have reduced capacity for autoregulation and so “may not effectively counteract sudden drops in blood pressure.

“Thus, intensive blood pressure lowering may further reduce blood flow ... and exacerbate ischemic injury.”

On the other hand, the conventional group confirmed prior studies indicating that high SBP is associated with poor outcomes.

Dr. Nam suggested that increased BP “may be a physiological response to the acute stress of stroke,” but that the adverse outcomes in some patients “might reflect stroke severity rather than being a direct effect of raised blood pressure.”

Session cochair Carlos Molina, MD, director of the stroke unit and brain hemodynamics at Vall d’Hebron Hospital, Barcelona, commented that “it’s very important to remember that the guidances are endorsed by the results of this study.

He said in an interview that “intensive blood pressure lowering harms the brain, especially just after reperfusion.

“So, the results are in line with the previous concept that we need to be careful, as intensive blood pressure lowering is associated with clinical deterioration and poor outcomes.”

He agreed with Dr. Nam that, with high BP also being harmful, the optimal range is currently unclear.

Dr. Molina underlined, however, that, in the absence of further studies, “we have to stick to the guidelines.”

Dr. Nam pointed out that, while high BP can result in reperfusion injury or ICH, “too low blood pressure can worsen cerebral ischemia.”

Yet the management of BP after successful recanalization with IAT is “largely unknown.”

He noted that, while both the European Stroke Organisation and American Heart Association/American Stroke Association guidelines recommend that BP should be kept below 180/105 mm Hg in patients who have undergone successful recanalization, the evidence class for this recommendation is “weak.”

Furthermore, observational studies have indicated that higher maximum or average SBP is associated with poor outcomes, but two multicenter clinical trials of intensive BP lowering after IAT, BP-TARGET and ENCHANTED2/MT, had conflicting results.

The researchers therefore investigated whether intensive BP management would result in better clinical outcomes in the 24 hours after successful recanalization with IAT.

They conducted a multicenter, open-label trial in which patients aged 20 years and older who underwent IAT for acute ischemic stroke with large cerebrovascular occlusion and had an SBP of at least 140 mm Hg were recruited from 19 centers in South Korea between June 2020 and November 2022.

The patients were randomly assigned within 2 hours of successful recanalization to intensive BP management, targeting an SBP less than 140 mm Hg, or conventional management, targeting an SBP of 140-180 mm Hg.

Clinicians could use local treatment protocols based on available intravenous BP-lowering drugs. BP was measured every 15 minutes for the first hour after randomization and then hourly for 24 hours.

The trial was terminated early because of safety concerns after the ENCHANTED2/MT trial revealed a negative impact on mRS scores at 3 months with intensive BP management.

Of 1,606 potentially eligible patients with acute ischemic stroke treated with IAT, 306 were randomly assigned, with 155 in the intensive group and 150 in the conventional group included in the primary analysis.

The mean age was 73.1 years, and 40.3% were women. The average National Institutes of Health Stroke Scale (NIHSS) score prior to IAT was 13. The mean time from stroke onset to randomization was 480 minutes (interquartile range, 320-820 minutes).

At 24 hours, the mean SBP in the intensive group was 129.2 mm Hg versus 138.0 mm Hg in the conventional group, for a between-group difference of 9.6 mm Hg (95% confidence interval, –12.2 to –6.9, P < .001).

Patients in the intensive group spent 80.3% of the first 24 hours with SBP less than 140 mm Hg versus 54.2% in the conventional group (P < .001). In contrast, conventional group patients spent 42.1% of the first 24 hours with SBP 140-180 mm Hg versus 14.2% in the intensive group.

Crucially, Dr. Nam showed that patients in the intensive BP-lowering group were significantly less likely than those in the conventional group to have a favorable outcome, defined as an mRS score of 0-2, at 3 months, at 39.4% versus 54.4%, or an adjusted odds ratio of 0.56 (95% CI, 0.33-0.96, P = .034).

Moreover, a poor outcome was 1.84 (95% CI, 1.17-2.91) times more common in the intervention group than the conventional group, Dr. Nam reported, with a number needed to harm of 6.6.

In terms of safety, there was no significant difference in rates of symptomatic ICH between the groups, at 9% in the intensive versus 8.1% in the conventional groups, or an aOR of 1.10 (95% CI, 0.48-2.53, P = .816).

There was also no difference in the rate of death related to the index stroke within 90 days, at 7.7% versus 5.4% (AOR, 1.73; 95% CI, 0.61-4.92, P = .307).

There were also no significant differences between the groups in key secondary outcomes, such as NIHSS score at 24 hours, recanalization at 24 hours, favorable outcome on the mRS at 1 month, and the EQ-5D-3L quality of life score.

However, patients in the intensive group were substantially more likely to experience malignant brain edema, at 7.7% versus 1.3% in the conventional group (aOR, 7.88; 95% CI, 1.57-39.39, P = .012).

Restricted cubic spline regression analysis indicated that there was a U-shaped relationship between mean SBP during the 24 hours following IAT and the odds ratio of a poor outcome, in which both a low and a high BPe were unfavorable.

Dr. Nam cautioned that, when interpreting the results, the early termination of the study may have reduced its statistical power and increased the likelihood of random and exaggerated treatment effects.

He also noted that the study was conducted in South Korea, and so the results may not be generalizable to other populations.

The study received a grant from the Patient-Centered Clinical Research Coordinating Center, funded by the Ministry of Health and Welfare. No relevant financial relationships were declared.

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

Giving very late thrombolysis to patients with large-vessel occlusion small core strokes did not show a significant benefit in the TIMELESS trial.

However, there were some encouraging trends, and there did not appear to be an increase in intracranial hemorrhage (ICH), leading to hope that the option of late thrombolysis in this group of patients may still have potential.

The TIMELESS study tested the approach of giving thrombolysis with tenecteplase (TNK) to patients with a large-vessel occlusion stroke up to 24 hours after symptom onset. Patients were selected by perfusion imaging, and those who had a stroke with a small core and large amount of salvageable brain tissue were included in the placebo-controlled study.

“This is first trial to try giving a thrombolytic so late – up to 24 hours after last known well. While we did not meet the primary outcome, there were some promising findings,” lead author, Gregory Albers, MD, director of the Stanford (Calif.) Stroke Center and professor of neurology at Stanford University, said in an interview.

“The most encouraging observation was that we did not show any safety issues with giving TNK to this population at such a late time. Many people thought this would be too high risk but there was no increase in ICH, which was very low and the same in both groups,” Dr. Albers said.

“And we saw some evidence of drug effect. There appeared to be a benefit in patients with M1 occlusions, the most common type of large-vessel occlusion, who represented half the patients in the study,” he added.

The researchers also gained information on the logistics and timing of TNK administration in this late period which they hope can guide the design of a future trial.

Dr. Albers presented the TIMELESS trial at the annual European Stroke Organisation Conference.

He explained that there is increasing evidence that intravenous thrombolysis can improve outcome in selected patients even beyond the traditional 4.5-hour time window.

The phase 3, double-blind, randomized, placebo-controlled TIMELESS study sought to investigate whether tenecteplase administered to patients with ischemic stroke with large-vessel occlusion presenting between 4.5 and 24 hours after last known well would improve clinical outcome as measured by modified Rankin Scale (mRS) at day 90.

The trial included 458 patients with an internal carotid artery occlusion or middle cerebral artery segment 1 or 2 occlusion and presenting with salvageable tissue on imaging. They were randomly assigned 1:1 to either intravenous tenecteplase (0.25 mg/kg; maximum, 25 mg) or placebo.

The proportion of patients treated with mechanical thrombectomy were similar between the two treatment arms (around 77%). The study completion rate was higher than 96% in both treatment arms.

The primary endpoint analyses showed no significant difference in the odds of a lower mRS score at day 90, but there was a slight trend toward benefit in the TNK group in the shift analysis, with a common odds ratio of 1.13 (95% confidence interval, 0.81-1.56; P = .48).

The percentage of patients achieving a favorable outcome, defined as an mRS of 0-2, was not significantly different between the treatment groups: 46% in the TNK group versus 42% in the placebo group (nominal P = .41).


 

Promising safety data

There were no significant safety issues, and the risk for bleeding was not significantly increased in the tenecteplase group. Symptomatic ICH occurred in 3.2% of the TNK group versus 2.3% of the placebo group, a nonsignificant difference.

“The low rate of ICH with TNK at this late time point is very reassuring,” Dr. Albers said. “We believe the reason for the low ICH rate is probably because these patients were selected for small core strokes. We also found that there was a trend towards the most benefit from TNK in patients with the smallest cores, supporting the use of imaging to select patients.”

The secondary endpoint of complete recanalization at 24-hours post randomization was higher in the TNK group at 76.7%, compared with 63.9% in the placebo group (P = .006).
 

Benefit in M1 occlusions?

Subgroup analysis showed that there appeared to be a benefit of TNK in the 227 patients included who had an M1 occlusion. In this group, the common odds ratio for a more favorable outcome in the mRS shift analysis with TNK was 1.59 (95% CI, 1.00-2.52; adjusted nominal P = .051).

The percentage of patients with a favorable outcome (mRS, 0-2) at 90 days in the M1 occlusion subgroup was 45.9% for TNK versus 31.4% for placebo, giving an adjusted odds ratio of 2.03 (95% CI, 1.14-3.66; nominal P = .017).

But Dr. Albers cautioned that this was an exploratory analysis, and no formal conclusions should be drawn from these data.

“We saw very strong results in favor of giving thrombolysis in the patients with M1 occlusions. We had preliminary pilot data suggesting this approach may work in these patients,” he commented.

“But we included the smaller M2 occlusions as well, because we thought that as there should be less clot in an M2 occlusion it might be easier to dissolve with thrombolysis,” he added. “But surprisingly, the M2 occlusion patients seemed to do worse with TNK than placebo, and the M1 patients did better.”
 

Timing of TNK

Dr. Albers said that there was also information from in the study on the timing of TNK administration.

In patients who also received thrombectomy, who made up of the majority of those in the study, the average time of TNK administration was only 20 minutes before the thrombectomy procedure.

“We had hoped to have a longer time between thrombolysis and thrombectomy so the drug would have more time to work. The idea was that patients would be given TNK at the primary stroke center before being transferred for thrombectomy, but actually only a few patients received TNK at the primary stroke center,” Dr. Albers explained.

“But, again surprisingly, we found that patients given TNK right at the time of the thrombectomy procedure seemed to show a trend toward benefit over placebo,” he reported.

He suggested that this may be caused by the thrombolytic dissolving the small fragments that can sometimes break off and cause further occlusions when the clot is removed by thrombectomy.

“We have learned a lot from this study, and we are planning to go forward with the information gained to plan a second study, in which we will focus on patients with M1 occlusions and try to get the drug on board at primary stroke centers, so it has more time to work before thrombectomy,” he added.

Commenting on the TIMELESS study at the ESOC meeting, Georgios Tsivgoulis, MD, professor of neurology, University of Athens, said that he thought the trial had shown three important results: “Firstly, TNK appeared to be safe in this late window in these selected patients – that is a very important observation. Secondly, reperfusion rates at 24 hours were increased with TNK and we know that this translates into clinical benefit. And thirdly, there was a neutral effect on primary outcomes, but I think the sample size of 438 patients was not large enough to show efficacy.”

Dr. Tsivgoulis concluded that these points need to be addressed in future trials.

The TIMELESS trial was funded by Genentech.

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

Giving very late thrombolysis to patients with large-vessel occlusion small core strokes did not show a significant benefit in the TIMELESS trial.

However, there were some encouraging trends, and there did not appear to be an increase in intracranial hemorrhage (ICH), leading to hope that the option of late thrombolysis in this group of patients may still have potential.

The TIMELESS study tested the approach of giving thrombolysis with tenecteplase (TNK) to patients with a large-vessel occlusion stroke up to 24 hours after symptom onset. Patients were selected by perfusion imaging, and those who had a stroke with a small core and large amount of salvageable brain tissue were included in the placebo-controlled study.

“This is first trial to try giving a thrombolytic so late – up to 24 hours after last known well. While we did not meet the primary outcome, there were some promising findings,” lead author, Gregory Albers, MD, director of the Stanford (Calif.) Stroke Center and professor of neurology at Stanford University, said in an interview.

“The most encouraging observation was that we did not show any safety issues with giving TNK to this population at such a late time. Many people thought this would be too high risk but there was no increase in ICH, which was very low and the same in both groups,” Dr. Albers said.

“And we saw some evidence of drug effect. There appeared to be a benefit in patients with M1 occlusions, the most common type of large-vessel occlusion, who represented half the patients in the study,” he added.

The researchers also gained information on the logistics and timing of TNK administration in this late period which they hope can guide the design of a future trial.

Dr. Albers presented the TIMELESS trial at the annual European Stroke Organisation Conference.

He explained that there is increasing evidence that intravenous thrombolysis can improve outcome in selected patients even beyond the traditional 4.5-hour time window.

The phase 3, double-blind, randomized, placebo-controlled TIMELESS study sought to investigate whether tenecteplase administered to patients with ischemic stroke with large-vessel occlusion presenting between 4.5 and 24 hours after last known well would improve clinical outcome as measured by modified Rankin Scale (mRS) at day 90.

The trial included 458 patients with an internal carotid artery occlusion or middle cerebral artery segment 1 or 2 occlusion and presenting with salvageable tissue on imaging. They were randomly assigned 1:1 to either intravenous tenecteplase (0.25 mg/kg; maximum, 25 mg) or placebo.

The proportion of patients treated with mechanical thrombectomy were similar between the two treatment arms (around 77%). The study completion rate was higher than 96% in both treatment arms.

The primary endpoint analyses showed no significant difference in the odds of a lower mRS score at day 90, but there was a slight trend toward benefit in the TNK group in the shift analysis, with a common odds ratio of 1.13 (95% confidence interval, 0.81-1.56; P = .48).

The percentage of patients achieving a favorable outcome, defined as an mRS of 0-2, was not significantly different between the treatment groups: 46% in the TNK group versus 42% in the placebo group (nominal P = .41).


 

Promising safety data

There were no significant safety issues, and the risk for bleeding was not significantly increased in the tenecteplase group. Symptomatic ICH occurred in 3.2% of the TNK group versus 2.3% of the placebo group, a nonsignificant difference.

“The low rate of ICH with TNK at this late time point is very reassuring,” Dr. Albers said. “We believe the reason for the low ICH rate is probably because these patients were selected for small core strokes. We also found that there was a trend towards the most benefit from TNK in patients with the smallest cores, supporting the use of imaging to select patients.”

The secondary endpoint of complete recanalization at 24-hours post randomization was higher in the TNK group at 76.7%, compared with 63.9% in the placebo group (P = .006).
 

Benefit in M1 occlusions?

Subgroup analysis showed that there appeared to be a benefit of TNK in the 227 patients included who had an M1 occlusion. In this group, the common odds ratio for a more favorable outcome in the mRS shift analysis with TNK was 1.59 (95% CI, 1.00-2.52; adjusted nominal P = .051).

The percentage of patients with a favorable outcome (mRS, 0-2) at 90 days in the M1 occlusion subgroup was 45.9% for TNK versus 31.4% for placebo, giving an adjusted odds ratio of 2.03 (95% CI, 1.14-3.66; nominal P = .017).

But Dr. Albers cautioned that this was an exploratory analysis, and no formal conclusions should be drawn from these data.

“We saw very strong results in favor of giving thrombolysis in the patients with M1 occlusions. We had preliminary pilot data suggesting this approach may work in these patients,” he commented.

“But we included the smaller M2 occlusions as well, because we thought that as there should be less clot in an M2 occlusion it might be easier to dissolve with thrombolysis,” he added. “But surprisingly, the M2 occlusion patients seemed to do worse with TNK than placebo, and the M1 patients did better.”
 

Timing of TNK

Dr. Albers said that there was also information from in the study on the timing of TNK administration.

In patients who also received thrombectomy, who made up of the majority of those in the study, the average time of TNK administration was only 20 minutes before the thrombectomy procedure.

“We had hoped to have a longer time between thrombolysis and thrombectomy so the drug would have more time to work. The idea was that patients would be given TNK at the primary stroke center before being transferred for thrombectomy, but actually only a few patients received TNK at the primary stroke center,” Dr. Albers explained.

“But, again surprisingly, we found that patients given TNK right at the time of the thrombectomy procedure seemed to show a trend toward benefit over placebo,” he reported.

He suggested that this may be caused by the thrombolytic dissolving the small fragments that can sometimes break off and cause further occlusions when the clot is removed by thrombectomy.

“We have learned a lot from this study, and we are planning to go forward with the information gained to plan a second study, in which we will focus on patients with M1 occlusions and try to get the drug on board at primary stroke centers, so it has more time to work before thrombectomy,” he added.

Commenting on the TIMELESS study at the ESOC meeting, Georgios Tsivgoulis, MD, professor of neurology, University of Athens, said that he thought the trial had shown three important results: “Firstly, TNK appeared to be safe in this late window in these selected patients – that is a very important observation. Secondly, reperfusion rates at 24 hours were increased with TNK and we know that this translates into clinical benefit. And thirdly, there was a neutral effect on primary outcomes, but I think the sample size of 438 patients was not large enough to show efficacy.”

Dr. Tsivgoulis concluded that these points need to be addressed in future trials.

The TIMELESS trial was funded by Genentech.

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

Giving very late thrombolysis to patients with large-vessel occlusion small core strokes did not show a significant benefit in the TIMELESS trial.

However, there were some encouraging trends, and there did not appear to be an increase in intracranial hemorrhage (ICH), leading to hope that the option of late thrombolysis in this group of patients may still have potential.

The TIMELESS study tested the approach of giving thrombolysis with tenecteplase (TNK) to patients with a large-vessel occlusion stroke up to 24 hours after symptom onset. Patients were selected by perfusion imaging, and those who had a stroke with a small core and large amount of salvageable brain tissue were included in the placebo-controlled study.

“This is first trial to try giving a thrombolytic so late – up to 24 hours after last known well. While we did not meet the primary outcome, there were some promising findings,” lead author, Gregory Albers, MD, director of the Stanford (Calif.) Stroke Center and professor of neurology at Stanford University, said in an interview.

“The most encouraging observation was that we did not show any safety issues with giving TNK to this population at such a late time. Many people thought this would be too high risk but there was no increase in ICH, which was very low and the same in both groups,” Dr. Albers said.

“And we saw some evidence of drug effect. There appeared to be a benefit in patients with M1 occlusions, the most common type of large-vessel occlusion, who represented half the patients in the study,” he added.

The researchers also gained information on the logistics and timing of TNK administration in this late period which they hope can guide the design of a future trial.

Dr. Albers presented the TIMELESS trial at the annual European Stroke Organisation Conference.

He explained that there is increasing evidence that intravenous thrombolysis can improve outcome in selected patients even beyond the traditional 4.5-hour time window.

The phase 3, double-blind, randomized, placebo-controlled TIMELESS study sought to investigate whether tenecteplase administered to patients with ischemic stroke with large-vessel occlusion presenting between 4.5 and 24 hours after last known well would improve clinical outcome as measured by modified Rankin Scale (mRS) at day 90.

The trial included 458 patients with an internal carotid artery occlusion or middle cerebral artery segment 1 or 2 occlusion and presenting with salvageable tissue on imaging. They were randomly assigned 1:1 to either intravenous tenecteplase (0.25 mg/kg; maximum, 25 mg) or placebo.

The proportion of patients treated with mechanical thrombectomy were similar between the two treatment arms (around 77%). The study completion rate was higher than 96% in both treatment arms.

The primary endpoint analyses showed no significant difference in the odds of a lower mRS score at day 90, but there was a slight trend toward benefit in the TNK group in the shift analysis, with a common odds ratio of 1.13 (95% confidence interval, 0.81-1.56; P = .48).

The percentage of patients achieving a favorable outcome, defined as an mRS of 0-2, was not significantly different between the treatment groups: 46% in the TNK group versus 42% in the placebo group (nominal P = .41).


 

Promising safety data

There were no significant safety issues, and the risk for bleeding was not significantly increased in the tenecteplase group. Symptomatic ICH occurred in 3.2% of the TNK group versus 2.3% of the placebo group, a nonsignificant difference.

“The low rate of ICH with TNK at this late time point is very reassuring,” Dr. Albers said. “We believe the reason for the low ICH rate is probably because these patients were selected for small core strokes. We also found that there was a trend towards the most benefit from TNK in patients with the smallest cores, supporting the use of imaging to select patients.”

The secondary endpoint of complete recanalization at 24-hours post randomization was higher in the TNK group at 76.7%, compared with 63.9% in the placebo group (P = .006).
 

Benefit in M1 occlusions?

Subgroup analysis showed that there appeared to be a benefit of TNK in the 227 patients included who had an M1 occlusion. In this group, the common odds ratio for a more favorable outcome in the mRS shift analysis with TNK was 1.59 (95% CI, 1.00-2.52; adjusted nominal P = .051).

The percentage of patients with a favorable outcome (mRS, 0-2) at 90 days in the M1 occlusion subgroup was 45.9% for TNK versus 31.4% for placebo, giving an adjusted odds ratio of 2.03 (95% CI, 1.14-3.66; nominal P = .017).

But Dr. Albers cautioned that this was an exploratory analysis, and no formal conclusions should be drawn from these data.

“We saw very strong results in favor of giving thrombolysis in the patients with M1 occlusions. We had preliminary pilot data suggesting this approach may work in these patients,” he commented.

“But we included the smaller M2 occlusions as well, because we thought that as there should be less clot in an M2 occlusion it might be easier to dissolve with thrombolysis,” he added. “But surprisingly, the M2 occlusion patients seemed to do worse with TNK than placebo, and the M1 patients did better.”
 

Timing of TNK

Dr. Albers said that there was also information from in the study on the timing of TNK administration.

In patients who also received thrombectomy, who made up of the majority of those in the study, the average time of TNK administration was only 20 minutes before the thrombectomy procedure.

“We had hoped to have a longer time between thrombolysis and thrombectomy so the drug would have more time to work. The idea was that patients would be given TNK at the primary stroke center before being transferred for thrombectomy, but actually only a few patients received TNK at the primary stroke center,” Dr. Albers explained.

“But, again surprisingly, we found that patients given TNK right at the time of the thrombectomy procedure seemed to show a trend toward benefit over placebo,” he reported.

He suggested that this may be caused by the thrombolytic dissolving the small fragments that can sometimes break off and cause further occlusions when the clot is removed by thrombectomy.

“We have learned a lot from this study, and we are planning to go forward with the information gained to plan a second study, in which we will focus on patients with M1 occlusions and try to get the drug on board at primary stroke centers, so it has more time to work before thrombectomy,” he added.

Commenting on the TIMELESS study at the ESOC meeting, Georgios Tsivgoulis, MD, professor of neurology, University of Athens, said that he thought the trial had shown three important results: “Firstly, TNK appeared to be safe in this late window in these selected patients – that is a very important observation. Secondly, reperfusion rates at 24 hours were increased with TNK and we know that this translates into clinical benefit. And thirdly, there was a neutral effect on primary outcomes, but I think the sample size of 438 patients was not large enough to show efficacy.”

Dr. Tsivgoulis concluded that these points need to be addressed in future trials.

The TIMELESS trial was funded by Genentech.

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