CHICAGO – Irrespective of the number of infliximab switches, multiple, successive switches from infliximab originator to biosimilars are effective and safe in patients with inflammatory bowel disease (IBD), according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).

“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.

While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.

The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.

During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)

Infliximab persistence

Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).

While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.

What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.

Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.

“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.

Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Irrespective of the number of infliximab switches, multiple, successive switches from infliximab originator to biosimilars are effective and safe in patients with inflammatory bowel disease (IBD), according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).

“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.

While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.

The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.

During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)

Infliximab persistence

Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).

While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.

What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.

Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.

“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.

Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Irrespective of the number of infliximab switches, multiple, successive switches from infliximab originator to biosimilars are effective and safe in patients with inflammatory bowel disease (IBD), according to analysis of a real world IBD cohort presented at the annual Digestive Disease Week® (DDW).

“These findings are of major socioeconomic importance, especially in low- and middle-income countries where the access to health care may be limited,” said study author Beatriz Gros, MD, an advanced clinical fellow in gastroenterology at Western General Hospital of Edinburgh.

While switching from originator infliximab to biosimilar infliximab is known observationally to be safe and effective, data on single and double switches are scarce, and are lacking on triple switches. Infliximab, the first monoclonal antibody biologic inhibiting anti–tumor necrosis factor was approved by the Food and Drug Administration and by the European Medicines Agency in 1998 and 1999, respectively. Economic pressures led to the development of biosimilars, with the first EMA approval in 2013 and FDA approval in 2016. Uptake in Europe has been broad and expanding following evidence that early therapy is associated with better outcomes. In the United States, a recent RAND Corporation study estimated savings to be $38.4 billion or 5.9% of projected total spending on biologics from 2021 to 2025, Dr. Gros reported.

The Edinburgh IBD unit has undertaken three switch programs starting with originator to CT-P13 in 2016, CT-P13 to SB2 in 2020, and SB2 to CT-P13 in 2021. Their prospective, observational cohort study assessing safety and efficacy after switching from SB2 to CT-P13 has, as a primary endpoint, CT-P13 persistence following the switch from SB2. Stratification of persistence according to the number of switches, effectiveness, immunogenicity, and safety were secondary outcomes.

During routine virtual biologic clinic care, researchers collected clinical disease activity scores (Harvey-Bradshaw Index; partial Mayo score), laboratory parameters (including C-reactive protein [CRP], IFX trough, and antibody levels), and fecal calprotectin on 297 IBD patients (median age, 37 years; 61.6% male). Among them, 67 had three switches, 138 had two switches, and 92 had one switch. Median disease duration was longer (11.4 years) for those with three switches than for two switches (6.3 years) or one switch (2.3 years) (P < .0001)

Infliximab persistence

Out of 297 patients, 269 (90.6%) remained on infliximab at week 24. Reasons for discontinuing treatment were immunogenicity (15/297; 5.1%), secondary loss of response (7/297, 2.4%), adverse events (3/297, 1%), patient’s choice (2/297, 0.7%), and primary nonresponse (1/297, 0.3%).

While infliximab persistence was 82.6%, 92.8% and 97% in patients with one, two and three infliximab switches, respectively (P = .003), after confounder adjustment, the number of switches was not independently associated with infliximab persistence, Dr. Gros said.

What factors actually did predict infliximab persistence? Multivariable analysis identified absence of biochemical remission (CRP > 5 mg/L [hazard ratio, 3.21; 95% confidence interval, 1.43-7.24]); a diagnosis of ulcerative colitis/ inflammatory bowel disease unclassified (HR, 2.69; 95% CI, 1.19-6.06), detectable antibodies against infliximab at switch (HR, 5.81; 95% CI, 2.27-12.84) and time on infliximab (HR, 0.77; 95% CI, 0.62-0.95) as independent predictors for infliximab persistence rather than number of infliximab switches.

Clinical (P = .77), biochemical (P = .75), and fecal biomarker (P = .63) remission rates, Dr. Gros reported, were comparable at baseline, week 12 and week 24, with baseline rates for clinical, biochemical and fecal biomarker remission at 79.4%, 85.2%, and 85.3%, respectively, and at 81%, 86.5%, and 84.4% at week 24.

“Immunogenicity has been a major concern regarding multiple switches, although both our study and previous literature demonstrated that this seemed to be not happening more often to patients who had multiple switches compared to those who had fewer or none. Our study found that, of the 14 (7.1%) patients who developed de novo antibodies, none of them underwent three switches,” she said.

Dr. Gros disclosed relationships with Pfizer, AbbVie, and Jansen.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Only 1%-3% of patients who have had bariatric surgery take Food and Drug Administration–approved antiobesity medications even though 25% of patients experience significant weight regain within a few years of surgery, according to a study presented at the annual Digestive Disease Week® meeting.

Obesity is a chronic, relapsing condition that must be treated as such, said the study’s author Stephen A. Firkins, MD, a fellow of gastroenterology and hepatology at the Cleveland Clinic. “Barriers to antiobesity medications must be identified.”

“If a quarter of all patients experience weight regain and another quarter experience insufficient weight loss – but only 5% are being prescribed an FDA-approved AOM – that means there’s underutilization,” Dr. Firkins said.

Data from the National Health and Nutrition Examination Survey show that 30.7% of all men and women in the United States are overweight and of these, 42.4% are obese. For the severely obese, bariatric surgery, including sleeve gastrectomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass, are viable options with differing degrees of long-term success.

And while antiobesity medications such as orlistat (Xenical, Alli), phentermine/topiramate (Qsymia), naltrexone/bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and setmelanotide (Imcivree), may be considered before bariatric surgery, there are questions about the need for its use after surgery.

“While these are often employed or considered presurgically, there is a paucity of literature describing their utilization postsurgically, particularly in regards to newer antiobesity medications such as the [glucagonlike peptide–1] receptor agonists,” Dr. Firkins said.

The aim of Dr. Firkins’ analysis of the large, publicly available IBM Explorys Electronic Health Record, which included 59,160 adult post–bariatric surgery patients, was to identify postoperative weight control medication use and trends among different populations.

He found rates of postsurgical weight control medication use at 8% for topiramate (off label), 2.9% for liraglutide, 1.03% for phentermine/topiramate, 0.95% for naltrexone/bupropion, 0.52% for semaglutide and 0.1% for orlistat. Rates of topiramate use were higher for patients in the 35- 39-year range, and for orlistat and liraglutide in the 65- to 69-year range.

The differences, Dr. Firkins said, were likely related to side-effect profiles and accumulations of comorbidities with advancing age. Black patients were more likely to be prescribed the medications. Also, further analysis showed a significantly higher use of these medications among individuals with hypertension, diabetes, and hyperlipidemia.

The analyses raised several questions for future study, Dr. Firkins said: “What is the optimal timing of antiobesity medication initiation? Is it at the plateau of peak weight loss typically seen at 1-3 years post surgery? Or, after weight is regained? What is the phenotype of patients who are going to be good responders versus poor responders to a particular medication category?”

“Upon recognition of insufficient weight loss/weight regain, a multidisciplinary strategy towards management is warranted, including behavioral and dietary counseling, and consideration of AOM early use, as well as endoscopic or surgical revision,” he said.

Dr. Firkins had no disclosures.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Only 1%-3% of patients who have had bariatric surgery take Food and Drug Administration–approved antiobesity medications even though 25% of patients experience significant weight regain within a few years of surgery, according to a study presented at the annual Digestive Disease Week® meeting.

Obesity is a chronic, relapsing condition that must be treated as such, said the study’s author Stephen A. Firkins, MD, a fellow of gastroenterology and hepatology at the Cleveland Clinic. “Barriers to antiobesity medications must be identified.”

“If a quarter of all patients experience weight regain and another quarter experience insufficient weight loss – but only 5% are being prescribed an FDA-approved AOM – that means there’s underutilization,” Dr. Firkins said.

Data from the National Health and Nutrition Examination Survey show that 30.7% of all men and women in the United States are overweight and of these, 42.4% are obese. For the severely obese, bariatric surgery, including sleeve gastrectomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass, are viable options with differing degrees of long-term success.

And while antiobesity medications such as orlistat (Xenical, Alli), phentermine/topiramate (Qsymia), naltrexone/bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and setmelanotide (Imcivree), may be considered before bariatric surgery, there are questions about the need for its use after surgery.

“While these are often employed or considered presurgically, there is a paucity of literature describing their utilization postsurgically, particularly in regards to newer antiobesity medications such as the [glucagonlike peptide–1] receptor agonists,” Dr. Firkins said.

The aim of Dr. Firkins’ analysis of the large, publicly available IBM Explorys Electronic Health Record, which included 59,160 adult post–bariatric surgery patients, was to identify postoperative weight control medication use and trends among different populations.

He found rates of postsurgical weight control medication use at 8% for topiramate (off label), 2.9% for liraglutide, 1.03% for phentermine/topiramate, 0.95% for naltrexone/bupropion, 0.52% for semaglutide and 0.1% for orlistat. Rates of topiramate use were higher for patients in the 35- 39-year range, and for orlistat and liraglutide in the 65- to 69-year range.

The differences, Dr. Firkins said, were likely related to side-effect profiles and accumulations of comorbidities with advancing age. Black patients were more likely to be prescribed the medications. Also, further analysis showed a significantly higher use of these medications among individuals with hypertension, diabetes, and hyperlipidemia.

The analyses raised several questions for future study, Dr. Firkins said: “What is the optimal timing of antiobesity medication initiation? Is it at the plateau of peak weight loss typically seen at 1-3 years post surgery? Or, after weight is regained? What is the phenotype of patients who are going to be good responders versus poor responders to a particular medication category?”

“Upon recognition of insufficient weight loss/weight regain, a multidisciplinary strategy towards management is warranted, including behavioral and dietary counseling, and consideration of AOM early use, as well as endoscopic or surgical revision,” he said.

Dr. Firkins had no disclosures.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

CHICAGO – Only 1%-3% of patients who have had bariatric surgery take Food and Drug Administration–approved antiobesity medications even though 25% of patients experience significant weight regain within a few years of surgery, according to a study presented at the annual Digestive Disease Week® meeting.

Obesity is a chronic, relapsing condition that must be treated as such, said the study’s author Stephen A. Firkins, MD, a fellow of gastroenterology and hepatology at the Cleveland Clinic. “Barriers to antiobesity medications must be identified.”

“If a quarter of all patients experience weight regain and another quarter experience insufficient weight loss – but only 5% are being prescribed an FDA-approved AOM – that means there’s underutilization,” Dr. Firkins said.

Data from the National Health and Nutrition Examination Survey show that 30.7% of all men and women in the United States are overweight and of these, 42.4% are obese. For the severely obese, bariatric surgery, including sleeve gastrectomy, Roux-en-Y gastric bypass, and one anastomosis gastric bypass, are viable options with differing degrees of long-term success.

And while antiobesity medications such as orlistat (Xenical, Alli), phentermine/topiramate (Qsymia), naltrexone/bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and setmelanotide (Imcivree), may be considered before bariatric surgery, there are questions about the need for its use after surgery.

“While these are often employed or considered presurgically, there is a paucity of literature describing their utilization postsurgically, particularly in regards to newer antiobesity medications such as the [glucagonlike peptide–1] receptor agonists,” Dr. Firkins said.

The aim of Dr. Firkins’ analysis of the large, publicly available IBM Explorys Electronic Health Record, which included 59,160 adult post–bariatric surgery patients, was to identify postoperative weight control medication use and trends among different populations.

He found rates of postsurgical weight control medication use at 8% for topiramate (off label), 2.9% for liraglutide, 1.03% for phentermine/topiramate, 0.95% for naltrexone/bupropion, 0.52% for semaglutide and 0.1% for orlistat. Rates of topiramate use were higher for patients in the 35- 39-year range, and for orlistat and liraglutide in the 65- to 69-year range.

The differences, Dr. Firkins said, were likely related to side-effect profiles and accumulations of comorbidities with advancing age. Black patients were more likely to be prescribed the medications. Also, further analysis showed a significantly higher use of these medications among individuals with hypertension, diabetes, and hyperlipidemia.

The analyses raised several questions for future study, Dr. Firkins said: “What is the optimal timing of antiobesity medication initiation? Is it at the plateau of peak weight loss typically seen at 1-3 years post surgery? Or, after weight is regained? What is the phenotype of patients who are going to be good responders versus poor responders to a particular medication category?”

“Upon recognition of insufficient weight loss/weight regain, a multidisciplinary strategy towards management is warranted, including behavioral and dietary counseling, and consideration of AOM early use, as well as endoscopic or surgical revision,” he said.

Dr. Firkins had no disclosures.

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and The Society for Surgery of the Alimentary Tract.

SAN FRANCISCO – Physically violent events at an inpatient psychiatric unit in Pennsylvania dropped by 59.8% in the months after it implemented a plan to administer antipsychotic medications to patients more quickly – both in the emergency department and in the unit – and improve handoffs between providers and nurses, researchers reported.

“We were able to significantly reduce violence,” said Michael Chen, MD, Lehigh Valley Health Network psychiatry resident and lead author of an abstract presented at the annual meeting of the American Psychiatric Association. “Furthermore, the interventions were effective in reducing episodes of violence rather than redirecting it. And the overall feeling of safety on the inpatient psychiatric unit improved.”

Violence is common in psychiatric units, although it’s not clear how often it occurs. “The data has shown that patients with a psychotic disorder such as schizophrenia or a mood disorder with psychotic features such as bipolar disorder tend to account for most of the episodes of violence on the unit,” Dr. Chen said in an interview. “This inevitably results in a higher risk for violence on inpatient psychiatric units as a large portion of patients admitted to inpatient psychiatric units have these diagnoses.”
 

Enlisting the pharmacy department

For the new study, investigators tracked episodes of violence – including verbal attacks – at an Allentown, Penn.–area inpatient psychiatric unit from December 2021 to September 2022. According to Dr. Chen, unit leaders implemented the new plan in May 2022 in the wake of higher levels of violence during the COVID-19 pandemic and the concurrent staff shortages.

Clinic leaders sought to identify potentially aggressive patients in the emergency department and treat them with antipsychotics prior to admission to the psychiatric unit, ensure that the pharmacy provides access to as-needed or standing medications, and develop “standardized huddles to ensure proper handoffs between providers and nurses.”

Medical staff relied on the Dynamic Appraisal of Situational Aggression scale, risk factors, and clinical judgment to determine which patients had the potential to be violent, Dr. Chen said.

As for treatment, first-line antipsychotics are typically given orally, but they can be injected if patients must be treated over their objections, he said. “We would only consider starting standing medications against objections in patients who are involuntarily committed.”

During the 5 months before the intervention was implemented versus the following 5 months, the average monthly number of physically violent events in the psychiatric unit fell from 12.4 to 4.8 (–61.1%, P = .04), and verbal threats dipped from 7.2 to 4 (–44.4%, P = .15). The total average number of violent events per month, including violence against property, fell from an average of 25.4 to 10.2 (–59.8%, P = .03).

The total patient population didn’t vary significantly over time, Dr. Chen said. “Thus, the decrease in violence was not correlated with a decrease in patient load.”

While “there were concerns that there would just be higher episodes of violence in the ED while psychiatry patients awaited placement,” Dr. Chen said, the numbers actually showed reductions in violence in that setting. The average number of physically violent events per month in the ED fell from 49.6 to 39.4 (–20.6%, P = .03). Verbal threats dropped from 38 to 34.6 (–8.9%, P = .5) and overall violent events dipped from 87.6 to 74 (–15.6%, P = .08).

Why did the interventions seem to work? “Standing doses as well as as-needed medications started for psychiatric patients in the emergency department have been crucial to prevent delay of care,” Dr. Chen said. Enlisting the pharmacy department “helped ensure all patients had appropriate as-needed medications to prevent them from decompensating on the units,” he added, and “involvement of nursing and ancillary staff in high-risk rounds allowed the treatment team to rapidly anticipate and address concerns.”

The study authors also reported that nursing staff felt safer. Scores on a perception-of-safety scale – with 1 most unsafe and 7 most safe – improved from 3.3 to 4.2 (+27%, P < .01).

Dr. Chen said there was a “minimal” increase in cost to implement the intervention, although coordination is necessary. “The emergency department and psychiatry department have to work together to initiate treatment in the ED while awaiting beds,” he said. “The treatment team needs to communicate concerns during rounds. The pharmacist and psychiatrist need to work together to ensure that proper as-needed medications are available.”
 

‘Good clinical practice’

In an interview, psychiatrist Mark J. Russ, MD, of NewYork-Presbyterian/Westchester Behavioral Health and Weill Cornell Medical College, said violent incidents in inpatient psychiatric units are influenced by many factors, such as history of violence, substance use, history of trauma, psychosis/paranoia, and medical problems.

The units themselves can contribute to the risk of violence through power struggles and lack of attention paid to respect and dignity, he said. “Attention to these issues is important in reducing violence,” he noted. “Generalized training for staff in de-escalation techniques and trauma-informed care is imperative. There may be value in developing specialized psychiatric ICUs where staff are meticulously trained in these and other approaches.”

The new study, Dr. Russ said, suggests that “early identification of patients at risk of engaging in violent behavior on the inpatient unit, pharmacologic treatment, and good communication helps reduce violence.” The findings, he added, suggest that “interventions known to constitute good clinical practice are indeed helpful.”

However, he cautioned that “treating all at-risk patients with antipsychotics, regardless of their psychiatric diagnosis, might well be considered chemical restraint, depending on [the] circumstances.”

There was no study funding. The study authors and Dr. Russ have no disclosures.

SAN FRANCISCO – Physically violent events at an inpatient psychiatric unit in Pennsylvania dropped by 59.8% in the months after it implemented a plan to administer antipsychotic medications to patients more quickly – both in the emergency department and in the unit – and improve handoffs between providers and nurses, researchers reported.

“We were able to significantly reduce violence,” said Michael Chen, MD, Lehigh Valley Health Network psychiatry resident and lead author of an abstract presented at the annual meeting of the American Psychiatric Association. “Furthermore, the interventions were effective in reducing episodes of violence rather than redirecting it. And the overall feeling of safety on the inpatient psychiatric unit improved.”

Violence is common in psychiatric units, although it’s not clear how often it occurs. “The data has shown that patients with a psychotic disorder such as schizophrenia or a mood disorder with psychotic features such as bipolar disorder tend to account for most of the episodes of violence on the unit,” Dr. Chen said in an interview. “This inevitably results in a higher risk for violence on inpatient psychiatric units as a large portion of patients admitted to inpatient psychiatric units have these diagnoses.”
 

Enlisting the pharmacy department

For the new study, investigators tracked episodes of violence – including verbal attacks – at an Allentown, Penn.–area inpatient psychiatric unit from December 2021 to September 2022. According to Dr. Chen, unit leaders implemented the new plan in May 2022 in the wake of higher levels of violence during the COVID-19 pandemic and the concurrent staff shortages.

Clinic leaders sought to identify potentially aggressive patients in the emergency department and treat them with antipsychotics prior to admission to the psychiatric unit, ensure that the pharmacy provides access to as-needed or standing medications, and develop “standardized huddles to ensure proper handoffs between providers and nurses.”

Medical staff relied on the Dynamic Appraisal of Situational Aggression scale, risk factors, and clinical judgment to determine which patients had the potential to be violent, Dr. Chen said.

As for treatment, first-line antipsychotics are typically given orally, but they can be injected if patients must be treated over their objections, he said. “We would only consider starting standing medications against objections in patients who are involuntarily committed.”

During the 5 months before the intervention was implemented versus the following 5 months, the average monthly number of physically violent events in the psychiatric unit fell from 12.4 to 4.8 (–61.1%, P = .04), and verbal threats dipped from 7.2 to 4 (–44.4%, P = .15). The total average number of violent events per month, including violence against property, fell from an average of 25.4 to 10.2 (–59.8%, P = .03).

The total patient population didn’t vary significantly over time, Dr. Chen said. “Thus, the decrease in violence was not correlated with a decrease in patient load.”

While “there were concerns that there would just be higher episodes of violence in the ED while psychiatry patients awaited placement,” Dr. Chen said, the numbers actually showed reductions in violence in that setting. The average number of physically violent events per month in the ED fell from 49.6 to 39.4 (–20.6%, P = .03). Verbal threats dropped from 38 to 34.6 (–8.9%, P = .5) and overall violent events dipped from 87.6 to 74 (–15.6%, P = .08).

Why did the interventions seem to work? “Standing doses as well as as-needed medications started for psychiatric patients in the emergency department have been crucial to prevent delay of care,” Dr. Chen said. Enlisting the pharmacy department “helped ensure all patients had appropriate as-needed medications to prevent them from decompensating on the units,” he added, and “involvement of nursing and ancillary staff in high-risk rounds allowed the treatment team to rapidly anticipate and address concerns.”

The study authors also reported that nursing staff felt safer. Scores on a perception-of-safety scale – with 1 most unsafe and 7 most safe – improved from 3.3 to 4.2 (+27%, P < .01).

Dr. Chen said there was a “minimal” increase in cost to implement the intervention, although coordination is necessary. “The emergency department and psychiatry department have to work together to initiate treatment in the ED while awaiting beds,” he said. “The treatment team needs to communicate concerns during rounds. The pharmacist and psychiatrist need to work together to ensure that proper as-needed medications are available.”
 

‘Good clinical practice’

In an interview, psychiatrist Mark J. Russ, MD, of NewYork-Presbyterian/Westchester Behavioral Health and Weill Cornell Medical College, said violent incidents in inpatient psychiatric units are influenced by many factors, such as history of violence, substance use, history of trauma, psychosis/paranoia, and medical problems.

The units themselves can contribute to the risk of violence through power struggles and lack of attention paid to respect and dignity, he said. “Attention to these issues is important in reducing violence,” he noted. “Generalized training for staff in de-escalation techniques and trauma-informed care is imperative. There may be value in developing specialized psychiatric ICUs where staff are meticulously trained in these and other approaches.”

The new study, Dr. Russ said, suggests that “early identification of patients at risk of engaging in violent behavior on the inpatient unit, pharmacologic treatment, and good communication helps reduce violence.” The findings, he added, suggest that “interventions known to constitute good clinical practice are indeed helpful.”

However, he cautioned that “treating all at-risk patients with antipsychotics, regardless of their psychiatric diagnosis, might well be considered chemical restraint, depending on [the] circumstances.”

There was no study funding. The study authors and Dr. Russ have no disclosures.

SAN FRANCISCO – Physically violent events at an inpatient psychiatric unit in Pennsylvania dropped by 59.8% in the months after it implemented a plan to administer antipsychotic medications to patients more quickly – both in the emergency department and in the unit – and improve handoffs between providers and nurses, researchers reported.

“We were able to significantly reduce violence,” said Michael Chen, MD, Lehigh Valley Health Network psychiatry resident and lead author of an abstract presented at the annual meeting of the American Psychiatric Association. “Furthermore, the interventions were effective in reducing episodes of violence rather than redirecting it. And the overall feeling of safety on the inpatient psychiatric unit improved.”

Violence is common in psychiatric units, although it’s not clear how often it occurs. “The data has shown that patients with a psychotic disorder such as schizophrenia or a mood disorder with psychotic features such as bipolar disorder tend to account for most of the episodes of violence on the unit,” Dr. Chen said in an interview. “This inevitably results in a higher risk for violence on inpatient psychiatric units as a large portion of patients admitted to inpatient psychiatric units have these diagnoses.”
 

Enlisting the pharmacy department

For the new study, investigators tracked episodes of violence – including verbal attacks – at an Allentown, Penn.–area inpatient psychiatric unit from December 2021 to September 2022. According to Dr. Chen, unit leaders implemented the new plan in May 2022 in the wake of higher levels of violence during the COVID-19 pandemic and the concurrent staff shortages.

Clinic leaders sought to identify potentially aggressive patients in the emergency department and treat them with antipsychotics prior to admission to the psychiatric unit, ensure that the pharmacy provides access to as-needed or standing medications, and develop “standardized huddles to ensure proper handoffs between providers and nurses.”

Medical staff relied on the Dynamic Appraisal of Situational Aggression scale, risk factors, and clinical judgment to determine which patients had the potential to be violent, Dr. Chen said.

As for treatment, first-line antipsychotics are typically given orally, but they can be injected if patients must be treated over their objections, he said. “We would only consider starting standing medications against objections in patients who are involuntarily committed.”

During the 5 months before the intervention was implemented versus the following 5 months, the average monthly number of physically violent events in the psychiatric unit fell from 12.4 to 4.8 (–61.1%, P = .04), and verbal threats dipped from 7.2 to 4 (–44.4%, P = .15). The total average number of violent events per month, including violence against property, fell from an average of 25.4 to 10.2 (–59.8%, P = .03).

The total patient population didn’t vary significantly over time, Dr. Chen said. “Thus, the decrease in violence was not correlated with a decrease in patient load.”

While “there were concerns that there would just be higher episodes of violence in the ED while psychiatry patients awaited placement,” Dr. Chen said, the numbers actually showed reductions in violence in that setting. The average number of physically violent events per month in the ED fell from 49.6 to 39.4 (–20.6%, P = .03). Verbal threats dropped from 38 to 34.6 (–8.9%, P = .5) and overall violent events dipped from 87.6 to 74 (–15.6%, P = .08).

Why did the interventions seem to work? “Standing doses as well as as-needed medications started for psychiatric patients in the emergency department have been crucial to prevent delay of care,” Dr. Chen said. Enlisting the pharmacy department “helped ensure all patients had appropriate as-needed medications to prevent them from decompensating on the units,” he added, and “involvement of nursing and ancillary staff in high-risk rounds allowed the treatment team to rapidly anticipate and address concerns.”

The study authors also reported that nursing staff felt safer. Scores on a perception-of-safety scale – with 1 most unsafe and 7 most safe – improved from 3.3 to 4.2 (+27%, P < .01).

Dr. Chen said there was a “minimal” increase in cost to implement the intervention, although coordination is necessary. “The emergency department and psychiatry department have to work together to initiate treatment in the ED while awaiting beds,” he said. “The treatment team needs to communicate concerns during rounds. The pharmacist and psychiatrist need to work together to ensure that proper as-needed medications are available.”
 

‘Good clinical practice’

In an interview, psychiatrist Mark J. Russ, MD, of NewYork-Presbyterian/Westchester Behavioral Health and Weill Cornell Medical College, said violent incidents in inpatient psychiatric units are influenced by many factors, such as history of violence, substance use, history of trauma, psychosis/paranoia, and medical problems.

The units themselves can contribute to the risk of violence through power struggles and lack of attention paid to respect and dignity, he said. “Attention to these issues is important in reducing violence,” he noted. “Generalized training for staff in de-escalation techniques and trauma-informed care is imperative. There may be value in developing specialized psychiatric ICUs where staff are meticulously trained in these and other approaches.”

The new study, Dr. Russ said, suggests that “early identification of patients at risk of engaging in violent behavior on the inpatient unit, pharmacologic treatment, and good communication helps reduce violence.” The findings, he added, suggest that “interventions known to constitute good clinical practice are indeed helpful.”

However, he cautioned that “treating all at-risk patients with antipsychotics, regardless of their psychiatric diagnosis, might well be considered chemical restraint, depending on [the] circumstances.”

There was no study funding. The study authors and Dr. Russ have no disclosures.

The Diagnosis: Actinic Prurigo

Actinic prurigo is an idiopathic photodermatosis triggered by UV exposure that primarily affects sun-exposed areas of the skin.^1,2 It typically presents as pruritic papules, plaques, and nodules, with most patients also experiencing oral tingling and pain.³ In more severe cases, it can progress to include conjunctival disease, scarring, and cheilitis.¹ A study of ocular findings among children with actinic pruritus reported that photophobia was one of the most important features,⁴ which was present in our patient. The face, especially over the zygomatic arches, nasal bridge, and lower lip, commonly is affected.1 Secondary lichenification or eczematization may occur.⁵ In our patient, the combination of conjunctivitis, cheilitis, and an eruption on sun-exposed skin were crucial in making the diagnosis.

Most cases present in patients younger than 10 years. It most commonly is seen in American Indians in North America, Central America, and South America.² After the diagnosis was considered in our patient, the family was asked about their ancestry and confirmed that both of the patient’s maternal and paternal grandparents were of American Indian descent. There also is a strong genetic component; the HLA-DR4 allele variant is present in 90% of cases, especially DRB1*0407, which is seen in 60% of cases.^1,6 In our patient, testing revealed HLA-DR4, DRB1*04 positivity. We further hypothesized that his mother’s photosensitive rash may have been actinic prurigo as opposed to polymorphous light eruption, which could explain the lack of response to hydroxychloroquine.

The diagnosis of actinic prurigo usually is made clinically. A skin biopsy typically is not necessary but would show hyperkeratosis, spongiosis, and acanthosis with a lymphocytic perivascular infiltrate. Biopsies of the lip classically show lymphoid germinal centers in the lamina propria, which can help distinguish actinic prurigo from polymorphous light eruption.¹

In our patient, the differential diagnosis included polymorphous light eruption, connective tissue disease such as lupus erythematosus or dermatomyositis, porphyria such as erythropoietic protoporphyria, and allergic contact dermatitis. Polymorphous light eruption was ruled out by the oral and ocular manifestations, which are not atypical for this diagnosis. The patient’s laboratory results displayed unremarkable antinuclear antibodies, creatine kinase, aldolase, and extractable nuclear antigens, which made connective tissue disease unlikely. Furthermore, a porphyria screen for total plasma porphyrins and whole blood protoporphyrin was negative, which helped rule out porphyria. Allergic contact dermatitis seemed less likely given the lack of improvement with topical steroids. Overall, the clinical presentation in a patient with relevant family ancestry and HLA-DR4 positivity supported a diagnosis of actinic prurigo.⁷

To manage the condition in our patient, strict photoprotection was recommended as well as the application of triamcinolone ointment 0.025% to the affected areas twice daily until the skin symptoms improved. For acute flares, other treatment considerations include topical tacrolimus, oral antihistamines, and oral corticosteroids. Some success has been reported with cyclosporine and azathioprine. For severe disease, thalidomide is the recommended treatment; it is effective in pediatric patients at dosages of 50 to 100 mg daily, but the dose has not yet been standardized for this age group.^8,9 Many adult patients initially are controlled with 100 to 200 mg daily, which can be tapered down to a dosage of 25 to 50 mg weekly with few adverse effects; however, the overall substantial side effects of thalidomide limit its use in both pediatric and adult populations.^1,2 Newer studies have suggested promising results with dupilumab, especially when actinic prurigo presents with high IgE levels or eosinophils on histology.^7,10 In our patient, the IgE level was normal.

The Diagnosis: Actinic Prurigo

Actinic prurigo is an idiopathic photodermatosis triggered by UV exposure that primarily affects sun-exposed areas of the skin.^1,2 It typically presents as pruritic papules, plaques, and nodules, with most patients also experiencing oral tingling and pain.³ In more severe cases, it can progress to include conjunctival disease, scarring, and cheilitis.¹ A study of ocular findings among children with actinic pruritus reported that photophobia was one of the most important features,⁴ which was present in our patient. The face, especially over the zygomatic arches, nasal bridge, and lower lip, commonly is affected.1 Secondary lichenification or eczematization may occur.⁵ In our patient, the combination of conjunctivitis, cheilitis, and an eruption on sun-exposed skin were crucial in making the diagnosis.

Most cases present in patients younger than 10 years. It most commonly is seen in American Indians in North America, Central America, and South America.² After the diagnosis was considered in our patient, the family was asked about their ancestry and confirmed that both of the patient’s maternal and paternal grandparents were of American Indian descent. There also is a strong genetic component; the HLA-DR4 allele variant is present in 90% of cases, especially DRB1*0407, which is seen in 60% of cases.^1,6 In our patient, testing revealed HLA-DR4, DRB1*04 positivity. We further hypothesized that his mother’s photosensitive rash may have been actinic prurigo as opposed to polymorphous light eruption, which could explain the lack of response to hydroxychloroquine.

The diagnosis of actinic prurigo usually is made clinically. A skin biopsy typically is not necessary but would show hyperkeratosis, spongiosis, and acanthosis with a lymphocytic perivascular infiltrate. Biopsies of the lip classically show lymphoid germinal centers in the lamina propria, which can help distinguish actinic prurigo from polymorphous light eruption.¹

In our patient, the differential diagnosis included polymorphous light eruption, connective tissue disease such as lupus erythematosus or dermatomyositis, porphyria such as erythropoietic protoporphyria, and allergic contact dermatitis. Polymorphous light eruption was ruled out by the oral and ocular manifestations, which are not atypical for this diagnosis. The patient’s laboratory results displayed unremarkable antinuclear antibodies, creatine kinase, aldolase, and extractable nuclear antigens, which made connective tissue disease unlikely. Furthermore, a porphyria screen for total plasma porphyrins and whole blood protoporphyrin was negative, which helped rule out porphyria. Allergic contact dermatitis seemed less likely given the lack of improvement with topical steroids. Overall, the clinical presentation in a patient with relevant family ancestry and HLA-DR4 positivity supported a diagnosis of actinic prurigo.⁷

To manage the condition in our patient, strict photoprotection was recommended as well as the application of triamcinolone ointment 0.025% to the affected areas twice daily until the skin symptoms improved. For acute flares, other treatment considerations include topical tacrolimus, oral antihistamines, and oral corticosteroids. Some success has been reported with cyclosporine and azathioprine. For severe disease, thalidomide is the recommended treatment; it is effective in pediatric patients at dosages of 50 to 100 mg daily, but the dose has not yet been standardized for this age group.^8,9 Many adult patients initially are controlled with 100 to 200 mg daily, which can be tapered down to a dosage of 25 to 50 mg weekly with few adverse effects; however, the overall substantial side effects of thalidomide limit its use in both pediatric and adult populations.^1,2 Newer studies have suggested promising results with dupilumab, especially when actinic prurigo presents with high IgE levels or eosinophils on histology.^7,10 In our patient, the IgE level was normal.

The Diagnosis: Actinic Prurigo

Actinic prurigo is an idiopathic photodermatosis triggered by UV exposure that primarily affects sun-exposed areas of the skin.^1,2 It typically presents as pruritic papules, plaques, and nodules, with most patients also experiencing oral tingling and pain.³ In more severe cases, it can progress to include conjunctival disease, scarring, and cheilitis.¹ A study of ocular findings among children with actinic pruritus reported that photophobia was one of the most important features,⁴ which was present in our patient. The face, especially over the zygomatic arches, nasal bridge, and lower lip, commonly is affected.1 Secondary lichenification or eczematization may occur.⁵ In our patient, the combination of conjunctivitis, cheilitis, and an eruption on sun-exposed skin were crucial in making the diagnosis.

Most cases present in patients younger than 10 years. It most commonly is seen in American Indians in North America, Central America, and South America.² After the diagnosis was considered in our patient, the family was asked about their ancestry and confirmed that both of the patient’s maternal and paternal grandparents were of American Indian descent. There also is a strong genetic component; the HLA-DR4 allele variant is present in 90% of cases, especially DRB1*0407, which is seen in 60% of cases.^1,6 In our patient, testing revealed HLA-DR4, DRB1*04 positivity. We further hypothesized that his mother’s photosensitive rash may have been actinic prurigo as opposed to polymorphous light eruption, which could explain the lack of response to hydroxychloroquine.

The diagnosis of actinic prurigo usually is made clinically. A skin biopsy typically is not necessary but would show hyperkeratosis, spongiosis, and acanthosis with a lymphocytic perivascular infiltrate. Biopsies of the lip classically show lymphoid germinal centers in the lamina propria, which can help distinguish actinic prurigo from polymorphous light eruption.¹

In our patient, the differential diagnosis included polymorphous light eruption, connective tissue disease such as lupus erythematosus or dermatomyositis, porphyria such as erythropoietic protoporphyria, and allergic contact dermatitis. Polymorphous light eruption was ruled out by the oral and ocular manifestations, which are not atypical for this diagnosis. The patient’s laboratory results displayed unremarkable antinuclear antibodies, creatine kinase, aldolase, and extractable nuclear antigens, which made connective tissue disease unlikely. Furthermore, a porphyria screen for total plasma porphyrins and whole blood protoporphyrin was negative, which helped rule out porphyria. Allergic contact dermatitis seemed less likely given the lack of improvement with topical steroids. Overall, the clinical presentation in a patient with relevant family ancestry and HLA-DR4 positivity supported a diagnosis of actinic prurigo.⁷

To manage the condition in our patient, strict photoprotection was recommended as well as the application of triamcinolone ointment 0.025% to the affected areas twice daily until the skin symptoms improved. For acute flares, other treatment considerations include topical tacrolimus, oral antihistamines, and oral corticosteroids. Some success has been reported with cyclosporine and azathioprine. For severe disease, thalidomide is the recommended treatment; it is effective in pediatric patients at dosages of 50 to 100 mg daily, but the dose has not yet been standardized for this age group.^8,9 Many adult patients initially are controlled with 100 to 200 mg daily, which can be tapered down to a dosage of 25 to 50 mg weekly with few adverse effects; however, the overall substantial side effects of thalidomide limit its use in both pediatric and adult populations.^1,2 Newer studies have suggested promising results with dupilumab, especially when actinic prurigo presents with high IgE levels or eosinophils on histology.^7,10 In our patient, the IgE level was normal.

MANNHEIM, GERMANY – Contrary to expectations, individuals with familial hypercholesterolemia (FH) have rates of overweight and obesity that mirror the general population – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.

Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.

Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.

Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.

She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”

The research was presented at the annual meeting of the European Atherosclerosis Society.
 

Tended to be thin

Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.

However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.

In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.

As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”

Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).

Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”

In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”

Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”

Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”

The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.

Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.

Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”

Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
 

More with than without

Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”

Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.

Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.

They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.

Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.

For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.

Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.

Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.

In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.

Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.

Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.

Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).

Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.

Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).

The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.

No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.

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

MANNHEIM, GERMANY – Contrary to expectations, individuals with familial hypercholesterolemia (FH) have rates of overweight and obesity that mirror the general population – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.

Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.

Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.

Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.

She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”

The research was presented at the annual meeting of the European Atherosclerosis Society.
 

Tended to be thin

Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.

However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.

In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.

As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”

Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).

Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”

In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”

Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”

Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”

The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.

Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.

Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”

Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
 

More with than without

Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”

Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.

Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.

They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.

Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.

For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.

Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.

Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.

In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.

Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.

Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.

Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).

Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.

Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).

The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.

No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.

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

MANNHEIM, GERMANY – Contrary to expectations, individuals with familial hypercholesterolemia (FH) have rates of overweight and obesity that mirror the general population – rates that appear to have a substantial impact on these patients’ already increased risk of coronary artery disease, a registry analysis suggests.

Data on almost 36,000 individuals with FH were collated from an international registry, revealing that 55% of adults and 25% of children and adolescents with the homozygous form of FH had overweight or obesity. The figures for heterozygous FH were 52% and 27%, respectively.

Crucially, overweight or obesity was associated with substantially increased rates of coronary artery disease, particularly in persons with heterozygous FH, among whom adults with obesity faced a twofold increased risk, rising to more than sixfold in children and adolescents.

Moreover, “obesity is associated with a worse lipid profile, even from childhood, regardless of whether a patient is on medication,” said study presenter Amany Elshorbagy, DPhil, Cardiovascular Epidemiologist, department of primary care and public health, Imperial College London.

She added that, with the increased risk of coronary artery disease associated with heterozygous FH, the results showed that “together with lipid-lowering medication, weight management is needed.”

The research was presented at the annual meeting of the European Atherosclerosis Society.
 

Tended to be thin

Alberico L. Catapano, MD, PhD, director of cardiovascular research and of the Lipoproteins and Atherosclerosis Laboratory of IRCCS Multimedica, Milan, and past president of the EAS, said in an interview that, historically, few FH patients were overweight or obese; rather, they tended to be thin.

However, there is now “a trend for people with FH to show more diabetes and obesity,” with the “bottom line” being that, as they are already at increased risk of coronary artery disease, it pushes their risk up even further.

In other words, if a risk factor such as obesity is added “on top of the strongest risk factor, that is LDL cholesterol, it is not one plus one makes two, it is one plus one makes three,” he said.

As such, Dr. Catapano believes that the study is “very interesting,” because it further underlines the importance of weight management for individuals with increased LDL cholesterol, “especially when you have genetic forms, like FH.”

Dr. Catapano’s comments were echoed by session co-chair Ulrike Schatz, MD, leader of the lipidology specialty department at the University Hospital Carl Gustav Carus, Technical University of Dresden (Germany).

Indeed, she told Dr. Elshorbagy before her presentation that she finds “a lot of my FH patients have a tendency towards anorexia.”

In an interview, Dr. Elshorbagy said that that reaction was typical of “most of the clinicians” she had spoken to. Upon seeing her data, especially for homozygous FH patients, they say, “They are on the lean side.”

Consequently, the research team went into the study “with the expectation that they might have a lower prevalence of obesity and overweight than the general population,” but “that’s not what we’re seeing.”

Dr. Elshorbagy noted that it would be helpful to have longitudinal data to determine whether, 50 years ago, patients with HF “were leaner, along with the rest of the population.”

The registry data are cross-sectional, and the team is now reaching out to the respective national lead investigators to submit follow-up data on their patients, with the aim of looking at changes in body weight and the impact on outcomes over time.

Another key question for the researchers is in regard to fat distribution, as body mass index “is not the best predictor of heart disease,” Dr. Elshorbagy said, but is rather central obesity.

Although they have also asked investigators to share waist circumference data, she conceded that it is a measurement that “is a lot harder to standardize across centers and countries; it’s not like putting patients on a scale.”

Overall, Dr. Elshorbagy believes that her findings indicate that clinicians should take a broader, more holistic approach toward their patients – in other words, an approach in which lipid lowering medication is “key but is just one of several things we need to do to make sure the coronary event rate goes down.”
 

More with than without

Dr. Elshorbagy began her presentation by highlighting that the prevalence of overweight and obesity ranges from 50% to 70% and that it is “the only health condition where you’ve got more people worldwide with the condition than without.”

Crucially, overweight increases the risk of coronary artery disease by approximately 20%. Among patients with obesity, the risk rises to 50%.

Given that FH patients “already have a very high risk of cardiovascular disease from their high cholesterol levels,” the team set out to determine rates of obesity and overweight in this population and their impact on coronary artery disease risk.

They used cross-sectional data from the EAS FH Studies Collaboration Global Registry, which involves 29,262 adults aged greater than or equal to 18 years and 6,275 children and adolescents aged 5 to 17 years with heterozygous FH, and 325 adults and 57 children with homozygous FH.

Dividing the adults into standard BMI categories, they found that 16% of heterozygous and 23% of homozygous FH patients had obesity, while 52% and 55%, respectively, had overweight or obesity.

For children, the team used World Health Organization z score cutoffs, which indicated that 9% of patients with heterozygous FH and 7% of patients with homozygous FH had obesity. Rates of overweight or obesity were 27% and 25%, respectively.

Among patients with heterozygous FH, rates of overweight or obesity among adults were 50% in high-income countries and 63% in other countries; among children, the rates were and 27% and 29%, respectively.

Stratified by region, the team found that the lowest rate of overweight or obesity among adult patients with heterozygous FH was in Eastern Asia, at 27%, while the highest was in Northern Africa/Western Asia (the Middle East), at 82%.

In North America, 56% of adult patients had overweight or obesity. The prevalence of coronary artery disease rose with increasing BMI.

Among adult patients with heterozygous FH, 11.3% of those with normal weight had coronary artery disease; the percentage rose to 22.9% among those with overweight, and 30.9% among those with obesity. Among children, the corresponding figures were 0.1%, 0.2%, and 0.7%.

Putting adults and children with homozygous FH together, the researchers found that 29.0% of patients with normal weight had coronary artery disease, compared with 31.3% of those with overweight and 49.3% of those with obesity.

Moreover, the results showed that levels of LDL and remnant cholesterol were significantly associated with BMI in adults and children with heterozygous FH, even after adjusting for age, sex, and lipid-lowering medication (P < .001 for all).

Multivariate analysis that took into account age, sex, lipid-lowering medication, and LDL cholesterol revealed that having obesity, compared with not having obesity, was associated with a substantial increase in the risk of coronary artery disease among patients with heterozygous FH.

Among adults with the condition, the odds ratio was 2.16 (95% confidence interval, 1.97-2.36), while among children and adolescents, it was 6.87 (95% CI, 1.55-30.46).

The results remained similar after further adjustment for the presence of diabetes and when considering peripheral artery disease and stroke.

No funding for the study was declared. Dr. Elshorbagy has relationships with Amgen, Daiichi Sankyo, and Regeneron.

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

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

An analysis of 61 cities in the United States where employers allow paid work absences for preventive medical services, such as breast and colon cancer screenings, shows that having the option of paid leave does in fact influence one’s decision to have preventive cancer screenings.

“Our results provide evidence for policymakers considering legislative or regulatory solutions to address insufficient screening adherence and highlight an understudied benefit of expanding paid sick leave coverage,” wrote authors who were led by Kevin Callison, PhD, of the Tulane University School of Public Health and Tropical Medicine, New Orleans.

The findings were published earlier this year in the New England Journal of Medicine.

Despite an Affordable Care Act provision eliminating most cost-sharing for cancer screening, the rate for recommended breast and colorectal cancer screening among U.S. adults is lower than 70%. Work commitments, time constraints, and the prospect of lost wages are frequently cited as contributing factors to this underuse of preventive care. Researchers hypothesized that having paid sick leave coverage for the use of preventive services could improve adherence to cancer screening guidelines. With continued failure to pass a bill mandating federal paid sick leave legislation, nearly 30% of the nation’s workforce lacks this coverage. Rates are lower for low-income workers, women, and underserved racial and ethnic groups, the authors write.

Coverage mandates have become politically contentious, as evidenced by the fact that their passage by some states (n = 17), counties (n = 4) and cities (n = 18) has been met by many states (n = 18) passing preemption laws banning municipalities from adopting the laws.

In this study, researchers examined the rate of colorectal and breast cancer screening at 12- and 24-month intervals among people living in one of 61 cities. Before paid sick leave mandates were put in place, cancer screening rates were similar across the board. But once mandates were put in place, cancer screening rates were higher among workers affected by the mandate by 1.31% (95% confidence interval, 0.28-2.34) for 12-month colorectal cancer screening, 1.56% (95% CI, 0.33-2.79) for 24-month colorectal cancer screening, 1.22% (95% CI, −0.20 to 2.64) for 12-month mammography, and 2.07% (95% CI, 0.15-3.99) for 24-month mammography.

“Although these appear to be modest effects, spread across a large population, these indicate a fairly substantial gain in cancer screenings,” Dr. Callison said.

Prior studies showing positive associations between having paid sick leave coverage and whether someone receives cancer screenings are likely confounded by selection bias because they compare workers who have such coverage to those who do not, Dr. Callison and colleagues state in their paper.

“Although the lack of paid sick leave coverage may hinder access to preventive care, current evidence is insufficient to draw meaningful conclusions about its relationship to cancer screening,” the authors write, citing that particularly health conscious workers may take jobs offering sick leave coverage.

Through quasi-experimental design, the present study aimed to overcome such confounding issues. Its analytic sample, using administrative data from the Merative MarketScan Research Databases, encompassed approximately 2.5 million person-specific records per year for the colorectal cancer screening sample. The researchers’ mammography sample included 1.3 million person-specific records per year of the period examined.

The associations cited above translate into relative colorectal cancer screening increases of 8.1% in the 12-month adjusted model and a 5.9% relative increase from the premandate rate in the 24-month adjusted model. The rate was 1.56 percentage points (95% CI, 0.33-2.79) higher in the cities subject to the paid sick leave mandates (a 5.9% relative increase from the premandate rate). For screening mammography in the cities subject to the mandates, the 12-month adjusted 1.22% increase (95% CI, –0.20 to 2.64) represented a 2.5% relative increase from the premandate level. The adjusted 24-month rate increase of 2.07% (95% CI, 0.15-4.00) represented a 3.3% relative increase from premandate rates.

“However, these estimates are averages across all workers in our sample, many of whom likely already had paid sick leave coverage prior to the enactment of a mandate,” Dr. Callison said in the interview. “In fact, in other work related to this project, we estimated that about 28% of private sector workers gain paid sick leave when a mandate is enacted. So then, if we scale our findings by the share of workers actually gaining paid sick leave coverage, our estimates are much larger – a 9%-12% increase in screening mammography and a 21%-29% increase in colorectal cancer screening.”

Dr. Callison and his team are in the process of developing a follow-up proposal that would examine the effects of paid sick leave on downstream outcomes of the cancer care continuum, such as timing from diagnosis to treatment initiation. “We also hope to examine who benefits from these additional screens and what they mean for health equity. Data limitations prevented us from exploring that issue in the current study,” he said.

Dr. Callison had no conflicts associated with this study.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

CHICAGO – The regular use of aspirin or other nonsteroidal anti-inflammatory drugs was found to be associated with a lower risk of early-onset conventional and advanced adenomas. The authors say that aspirin could prove to be an effective strategy in preventing early-onset colorectal cancer cases.

“What we have here is a 15% reduction for all adenomas and 33% for those with advanced histology, which to us is quite substantial. We have not seen that much [33%] in previous studies so I would think it definitely needs more study,” said Cassandra D. Fritz, MD, MPHS, a gastroenterologist with Washington University, St. Louis, in an oral presentation given at the annual Digestive Disease Week^®.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts,” Dr. Fritz said. Early-onset colorectal cancer cases have doubled since 1995, she said.

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk. In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years follow-up.

While emerging data have suggested that aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use are associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer. An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma. The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32,058 women who had at least one colonoscopy before age 50 (1991-2015). High-risk adenomas included those that were at least 1 cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1,247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions, was lower than in those who did not take aspirin and/or NSAIDs regularly. While the association was similar for high-risk vs. low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Dr. Cao said.

The U.S. Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start 5 years sooner at age 45. “As we know,” Dr. Yin said, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

DDW is sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Dr. Fritz had no disclosures and Dr. Cao listed consulting for Geneoscopy.

MUNICH, GERMANY – Anticoagulation using apixaban (Eliquis) offers no benefit over aspirin in patients with embolic stroke of undetermined source (ESUS) who have atrial cardiopathy but no overt atrial fibrillation, suggest findings from the ARCADIA trial.

The trial, which was halted early, randomized more than 1,000 ESUS patients with atrial cardiomyopathy to apixaban or placebo. Results showed that apixaban did not improve rates of recurrent stroke of any kind nor safety outcomes such as major hemorrhage and all-cause mortality.

The results were presented at the annual meeting of the European Stroke Organisation Conference.

“We found no benefit of apixaban over aspirin in patients with ESUS who had evidence of atrial cardiopathy, at least based on the criteria in our trial,” said study presenter Hooman Kamel, MD, MS, vice chair for research and chief of neurocritical care in the department of neurology, Weill Cornell Medicine, New York.

“It could be that this concept of thrombogenic atrial cardiopathy really isn’t present unless there is also atrial fibrillation,” he continued, suggesting alternatively that results may be caused by the “incorrect choice of atrial cardiopathy biomarkers or thresholds.”

“We chose these because they were clinically scalable and usable in a multicenter design,” Dr. Kamel explained, adding that there are a number of different proposed biomarkers that could be used in a future study.

The team will now perform secondary analyses over the coming months to “try to help sort out some of these potential explanations.”

Dr. Kamel concluded, however, that, “as of now, no strategy of anticoagulation has been found to be better than antiplatelet therapy for secondary stroke prevention after ESUS.”
 

Similar results

Approached for comment, session cochair Robin Lemmens, MD, PhD, a neurologist in the department of neurosciences, UZ Leuven (Belgium), noted that this is the third ESUS trial, after the NAVIGATE and RE-SPECT trials, and they have all showed “similar results.”

He said, however, that there “could be various reasons for that, and it’s good that they mentioned looking into the subgroups,” as has been done for those other studies.

“Most of these trials were initiated under the concept that most of these patients would have had underlying atrial fibrillation, and then of course there would have been a benefit for anticoagulation.”

“It turns out that that’s not the case,” Dr. Lemmens said, “probably because there’s a lot of heterogeneity in these patients,” with different reasons for developing stroke, “not just only potentially underlying atrial fibrillation.”

Session cochair Arthur Liesz, MD, PhD, Institute for Stroke and Dementia Research, University Hospital, LMU Munich, added that it is important to consider the definition of atrial cardiopathy in this context.

If this was limited only to structural cardiopathy, then this “was a rather small subpopulation in this study,” he said in an interview.

Dr. Liesz said that it could instead have been conducted with “more stringent cutoffs,” and could have considered blood biomarkers, “which then would have delivered more overlap with structural cardiopathy,” and allowed those patients to be analyzed separately.
 

Heterogeneous etiologies?

Dr. Kamel began by noting that the failure of NAVIGATE and RESPECT to show a benefit from anticoagulation in the prevention of recurrent stroke in patients with ESUS led to the hypothesis that this is “perhaps due to heterogeneous underlying etiologies.”

Moreover, these etiologies “may require different types of antithrombotic therapy to best prevent recurrence, and one such underlying etiology may be atrial cardiopathy.”

He explained that several observational studies have found, in the absence of atrial fibrillation, associations between stroke and different markers of atrial cardiopathy and, “given the proven benefit of anticoagulation in preventing strokes in patients with atrial fibrillation, it seems plausible” that they may also benefit.

To investigate further, the team conducted ARCADIA, an investigator-initiated, multicenter, randomized trial involving patients aged 45 years and older from 185 sites in the United States and Canada with a clinical diagnosis of stroke that met the consensus criteria for ESUS.

They also were required to have undergone brain imaging to rule out hemorrhagic stroke, and to have a modified Rankin Scale score of 4 or less, indicating up to a moderately severe degree of disability.

They also had atrial cardiopathy, as determined by P-wave terminal force in V1 greater than 5,000mcV*ms on electrocardiography, serum N-terminal prohormone of brain natriuretic peptide levels greater than 250 pg/mL, or a left atrium diameter of at least 3 cm/m².

The patients were randomly assigned to apixaban 5 mg or 2.5 mg twice daily plus aspirin placebo, or apixaban placebo plus aspirin 81 mg daily. Those diagnosed with atrial fibrillation after randomization crossed over to open-label anticoagulant therapy at physician discretion.

Dr. Kamel reported that, in 2022, after enrollment of 1015 patients with a mean follow-up of 1.8 years, the trial was halted at the planned interim efficacy/futility analysis, adding that there were “no safety concerns.”

The apixaban and aspirin groups were well balanced in terms of their baseline characteristics. The mean age was 68 years, and 54% were female. Three-quarters of the participants were White; 21.1% were Black.

Prior stroke was reported in 19% of patients. Hypertension was common, in about 77%, and type 2 diabetes was seen in 31%. There were relatively few cases of ischemic heart disease, heart failure, and peripheral arterial disease.

The primary efficacy outcome of recurrent stroke of any type occurred in 4.4% of both patients treated with apixaban and those given aspirin, at a hazard ratio of 1.00 (95% confidence interval, 0.64-1.55). Similar findings were seen when looking individually at ischemic and hemorrhagic stroke, and stroke of undetermined type.

There was also no significant difference in the secondary outcomes of recurrent ischemic stroke or systemic embolism, at 4.1% versus 4.4% (HR, 0.92; 95% CI, 0.59-1.44), and recurrent stroke of any type or death from any cause, at 7.3% versus 6.8% (HR, 1.08; 95% CI, 0.76-1.52).

In terms of safety, rates of major hemorrhage were low and almost identical between the groups, at 0.7% with apixaban and 0.8% for aspirin (HR, 1.02; 95% CI, 0.29-3.51), and were similar for all-cause mortality, at 1.8% versus 1.2% (HR, 1.53; 95% CI, 0.63-3.74).

Proportionately more patients treated with aspirin experienced symptomatic intracranial hemorrhage, at 1.1% versus 0%.

The trial results generated a flurry of interest on Twitter.

Thomas Ford, MD, a vascular neurology fellow from Boston Medical Center, described the results as “disappointing,” although he was “curious to see if there was any signal of benefit in subgroup analyses.”

Shadi Yaghi, codirector of the Comprehensive Stroke Center at Brown University, Providence, R.I., added that the trial “begs the question [as to] whether all device-detected atrial fibrillation warrants anticoagulation.”

Replying, Mitchell Elkind, MD, MPhil, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said that he agrees with this interpretation.

“Maybe the issue is not with the concept of atrial cardiopathy but with the need to [anticoagulate] all patients with low [atrial fibrillation] burden or incidental [atrial fibrillation] after stroke.”

The study was funded by the National Institutes of Health and the National Institute of Neurological Disorders and Stroke. The study drug was provided in kind by BMS-Pfizer, and ancillary funding for the NTproBNP assays was provided by Roche. No relevant financial relationships were reported.

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

MUNICH, GERMANY – Anticoagulation using apixaban (Eliquis) offers no benefit over aspirin in patients with embolic stroke of undetermined source (ESUS) who have atrial cardiopathy but no overt atrial fibrillation, suggest findings from the ARCADIA trial.

The trial, which was halted early, randomized more than 1,000 ESUS patients with atrial cardiomyopathy to apixaban or placebo. Results showed that apixaban did not improve rates of recurrent stroke of any kind nor safety outcomes such as major hemorrhage and all-cause mortality.

The results were presented at the annual meeting of the European Stroke Organisation Conference.

“We found no benefit of apixaban over aspirin in patients with ESUS who had evidence of atrial cardiopathy, at least based on the criteria in our trial,” said study presenter Hooman Kamel, MD, MS, vice chair for research and chief of neurocritical care in the department of neurology, Weill Cornell Medicine, New York.

“It could be that this concept of thrombogenic atrial cardiopathy really isn’t present unless there is also atrial fibrillation,” he continued, suggesting alternatively that results may be caused by the “incorrect choice of atrial cardiopathy biomarkers or thresholds.”

“We chose these because they were clinically scalable and usable in a multicenter design,” Dr. Kamel explained, adding that there are a number of different proposed biomarkers that could be used in a future study.

The team will now perform secondary analyses over the coming months to “try to help sort out some of these potential explanations.”

Dr. Kamel concluded, however, that, “as of now, no strategy of anticoagulation has been found to be better than antiplatelet therapy for secondary stroke prevention after ESUS.”
 

Similar results

Approached for comment, session cochair Robin Lemmens, MD, PhD, a neurologist in the department of neurosciences, UZ Leuven (Belgium), noted that this is the third ESUS trial, after the NAVIGATE and RE-SPECT trials, and they have all showed “similar results.”

He said, however, that there “could be various reasons for that, and it’s good that they mentioned looking into the subgroups,” as has been done for those other studies.

“Most of these trials were initiated under the concept that most of these patients would have had underlying atrial fibrillation, and then of course there would have been a benefit for anticoagulation.”

“It turns out that that’s not the case,” Dr. Lemmens said, “probably because there’s a lot of heterogeneity in these patients,” with different reasons for developing stroke, “not just only potentially underlying atrial fibrillation.”

Session cochair Arthur Liesz, MD, PhD, Institute for Stroke and Dementia Research, University Hospital, LMU Munich, added that it is important to consider the definition of atrial cardiopathy in this context.

If this was limited only to structural cardiopathy, then this “was a rather small subpopulation in this study,” he said in an interview.

Dr. Liesz said that it could instead have been conducted with “more stringent cutoffs,” and could have considered blood biomarkers, “which then would have delivered more overlap with structural cardiopathy,” and allowed those patients to be analyzed separately.
 

Heterogeneous etiologies?

Dr. Kamel began by noting that the failure of NAVIGATE and RESPECT to show a benefit from anticoagulation in the prevention of recurrent stroke in patients with ESUS led to the hypothesis that this is “perhaps due to heterogeneous underlying etiologies.”

Moreover, these etiologies “may require different types of antithrombotic therapy to best prevent recurrence, and one such underlying etiology may be atrial cardiopathy.”

He explained that several observational studies have found, in the absence of atrial fibrillation, associations between stroke and different markers of atrial cardiopathy and, “given the proven benefit of anticoagulation in preventing strokes in patients with atrial fibrillation, it seems plausible” that they may also benefit.

To investigate further, the team conducted ARCADIA, an investigator-initiated, multicenter, randomized trial involving patients aged 45 years and older from 185 sites in the United States and Canada with a clinical diagnosis of stroke that met the consensus criteria for ESUS.

They also were required to have undergone brain imaging to rule out hemorrhagic stroke, and to have a modified Rankin Scale score of 4 or less, indicating up to a moderately severe degree of disability.

They also had atrial cardiopathy, as determined by P-wave terminal force in V1 greater than 5,000mcV*ms on electrocardiography, serum N-terminal prohormone of brain natriuretic peptide levels greater than 250 pg/mL, or a left atrium diameter of at least 3 cm/m².

The patients were randomly assigned to apixaban 5 mg or 2.5 mg twice daily plus aspirin placebo, or apixaban placebo plus aspirin 81 mg daily. Those diagnosed with atrial fibrillation after randomization crossed over to open-label anticoagulant therapy at physician discretion.

Dr. Kamel reported that, in 2022, after enrollment of 1015 patients with a mean follow-up of 1.8 years, the trial was halted at the planned interim efficacy/futility analysis, adding that there were “no safety concerns.”

The apixaban and aspirin groups were well balanced in terms of their baseline characteristics. The mean age was 68 years, and 54% were female. Three-quarters of the participants were White; 21.1% were Black.

Prior stroke was reported in 19% of patients. Hypertension was common, in about 77%, and type 2 diabetes was seen in 31%. There were relatively few cases of ischemic heart disease, heart failure, and peripheral arterial disease.

The primary efficacy outcome of recurrent stroke of any type occurred in 4.4% of both patients treated with apixaban and those given aspirin, at a hazard ratio of 1.00 (95% confidence interval, 0.64-1.55). Similar findings were seen when looking individually at ischemic and hemorrhagic stroke, and stroke of undetermined type.

There was also no significant difference in the secondary outcomes of recurrent ischemic stroke or systemic embolism, at 4.1% versus 4.4% (HR, 0.92; 95% CI, 0.59-1.44), and recurrent stroke of any type or death from any cause, at 7.3% versus 6.8% (HR, 1.08; 95% CI, 0.76-1.52).

In terms of safety, rates of major hemorrhage were low and almost identical between the groups, at 0.7% with apixaban and 0.8% for aspirin (HR, 1.02; 95% CI, 0.29-3.51), and were similar for all-cause mortality, at 1.8% versus 1.2% (HR, 1.53; 95% CI, 0.63-3.74).

Proportionately more patients treated with aspirin experienced symptomatic intracranial hemorrhage, at 1.1% versus 0%.

The trial results generated a flurry of interest on Twitter.

Thomas Ford, MD, a vascular neurology fellow from Boston Medical Center, described the results as “disappointing,” although he was “curious to see if there was any signal of benefit in subgroup analyses.”

Shadi Yaghi, codirector of the Comprehensive Stroke Center at Brown University, Providence, R.I., added that the trial “begs the question [as to] whether all device-detected atrial fibrillation warrants anticoagulation.”

Replying, Mitchell Elkind, MD, MPhil, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said that he agrees with this interpretation.

“Maybe the issue is not with the concept of atrial cardiopathy but with the need to [anticoagulate] all patients with low [atrial fibrillation] burden or incidental [atrial fibrillation] after stroke.”

The study was funded by the National Institutes of Health and the National Institute of Neurological Disorders and Stroke. The study drug was provided in kind by BMS-Pfizer, and ancillary funding for the NTproBNP assays was provided by Roche. No relevant financial relationships were reported.

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

MUNICH, GERMANY – Anticoagulation using apixaban (Eliquis) offers no benefit over aspirin in patients with embolic stroke of undetermined source (ESUS) who have atrial cardiopathy but no overt atrial fibrillation, suggest findings from the ARCADIA trial.

The trial, which was halted early, randomized more than 1,000 ESUS patients with atrial cardiomyopathy to apixaban or placebo. Results showed that apixaban did not improve rates of recurrent stroke of any kind nor safety outcomes such as major hemorrhage and all-cause mortality.

The results were presented at the annual meeting of the European Stroke Organisation Conference.

“We found no benefit of apixaban over aspirin in patients with ESUS who had evidence of atrial cardiopathy, at least based on the criteria in our trial,” said study presenter Hooman Kamel, MD, MS, vice chair for research and chief of neurocritical care in the department of neurology, Weill Cornell Medicine, New York.

“It could be that this concept of thrombogenic atrial cardiopathy really isn’t present unless there is also atrial fibrillation,” he continued, suggesting alternatively that results may be caused by the “incorrect choice of atrial cardiopathy biomarkers or thresholds.”

“We chose these because they were clinically scalable and usable in a multicenter design,” Dr. Kamel explained, adding that there are a number of different proposed biomarkers that could be used in a future study.

The team will now perform secondary analyses over the coming months to “try to help sort out some of these potential explanations.”

Dr. Kamel concluded, however, that, “as of now, no strategy of anticoagulation has been found to be better than antiplatelet therapy for secondary stroke prevention after ESUS.”
 

Similar results

Approached for comment, session cochair Robin Lemmens, MD, PhD, a neurologist in the department of neurosciences, UZ Leuven (Belgium), noted that this is the third ESUS trial, after the NAVIGATE and RE-SPECT trials, and they have all showed “similar results.”

He said, however, that there “could be various reasons for that, and it’s good that they mentioned looking into the subgroups,” as has been done for those other studies.

“Most of these trials were initiated under the concept that most of these patients would have had underlying atrial fibrillation, and then of course there would have been a benefit for anticoagulation.”

“It turns out that that’s not the case,” Dr. Lemmens said, “probably because there’s a lot of heterogeneity in these patients,” with different reasons for developing stroke, “not just only potentially underlying atrial fibrillation.”

Session cochair Arthur Liesz, MD, PhD, Institute for Stroke and Dementia Research, University Hospital, LMU Munich, added that it is important to consider the definition of atrial cardiopathy in this context.

If this was limited only to structural cardiopathy, then this “was a rather small subpopulation in this study,” he said in an interview.

Dr. Liesz said that it could instead have been conducted with “more stringent cutoffs,” and could have considered blood biomarkers, “which then would have delivered more overlap with structural cardiopathy,” and allowed those patients to be analyzed separately.
 

Heterogeneous etiologies?

Dr. Kamel began by noting that the failure of NAVIGATE and RESPECT to show a benefit from anticoagulation in the prevention of recurrent stroke in patients with ESUS led to the hypothesis that this is “perhaps due to heterogeneous underlying etiologies.”

Moreover, these etiologies “may require different types of antithrombotic therapy to best prevent recurrence, and one such underlying etiology may be atrial cardiopathy.”

He explained that several observational studies have found, in the absence of atrial fibrillation, associations between stroke and different markers of atrial cardiopathy and, “given the proven benefit of anticoagulation in preventing strokes in patients with atrial fibrillation, it seems plausible” that they may also benefit.

To investigate further, the team conducted ARCADIA, an investigator-initiated, multicenter, randomized trial involving patients aged 45 years and older from 185 sites in the United States and Canada with a clinical diagnosis of stroke that met the consensus criteria for ESUS.

They also were required to have undergone brain imaging to rule out hemorrhagic stroke, and to have a modified Rankin Scale score of 4 or less, indicating up to a moderately severe degree of disability.

They also had atrial cardiopathy, as determined by P-wave terminal force in V1 greater than 5,000mcV*ms on electrocardiography, serum N-terminal prohormone of brain natriuretic peptide levels greater than 250 pg/mL, or a left atrium diameter of at least 3 cm/m².

The patients were randomly assigned to apixaban 5 mg or 2.5 mg twice daily plus aspirin placebo, or apixaban placebo plus aspirin 81 mg daily. Those diagnosed with atrial fibrillation after randomization crossed over to open-label anticoagulant therapy at physician discretion.

Dr. Kamel reported that, in 2022, after enrollment of 1015 patients with a mean follow-up of 1.8 years, the trial was halted at the planned interim efficacy/futility analysis, adding that there were “no safety concerns.”

The apixaban and aspirin groups were well balanced in terms of their baseline characteristics. The mean age was 68 years, and 54% were female. Three-quarters of the participants were White; 21.1% were Black.

Prior stroke was reported in 19% of patients. Hypertension was common, in about 77%, and type 2 diabetes was seen in 31%. There were relatively few cases of ischemic heart disease, heart failure, and peripheral arterial disease.

The primary efficacy outcome of recurrent stroke of any type occurred in 4.4% of both patients treated with apixaban and those given aspirin, at a hazard ratio of 1.00 (95% confidence interval, 0.64-1.55). Similar findings were seen when looking individually at ischemic and hemorrhagic stroke, and stroke of undetermined type.

There was also no significant difference in the secondary outcomes of recurrent ischemic stroke or systemic embolism, at 4.1% versus 4.4% (HR, 0.92; 95% CI, 0.59-1.44), and recurrent stroke of any type or death from any cause, at 7.3% versus 6.8% (HR, 1.08; 95% CI, 0.76-1.52).

In terms of safety, rates of major hemorrhage were low and almost identical between the groups, at 0.7% with apixaban and 0.8% for aspirin (HR, 1.02; 95% CI, 0.29-3.51), and were similar for all-cause mortality, at 1.8% versus 1.2% (HR, 1.53; 95% CI, 0.63-3.74).

Proportionately more patients treated with aspirin experienced symptomatic intracranial hemorrhage, at 1.1% versus 0%.

The trial results generated a flurry of interest on Twitter.

Thomas Ford, MD, a vascular neurology fellow from Boston Medical Center, described the results as “disappointing,” although he was “curious to see if there was any signal of benefit in subgroup analyses.”

Shadi Yaghi, codirector of the Comprehensive Stroke Center at Brown University, Providence, R.I., added that the trial “begs the question [as to] whether all device-detected atrial fibrillation warrants anticoagulation.”

Replying, Mitchell Elkind, MD, MPhil, professor of neurology and epidemiology at Columbia University Irving Medical Center, New York, said that he agrees with this interpretation.

“Maybe the issue is not with the concept of atrial cardiopathy but with the need to [anticoagulate] all patients with low [atrial fibrillation] burden or incidental [atrial fibrillation] after stroke.”

The study was funded by the National Institutes of Health and the National Institute of Neurological Disorders and Stroke. The study drug was provided in kind by BMS-Pfizer, and ancillary funding for the NTproBNP assays was provided by Roche. No relevant financial relationships were reported.

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

The most common adverse events were acne, headache, upper respiratory tract infection, creatine phosphokinase (CPK) level elevations, and nasopharyngitis. I'm confident that none of my patients will have CPK elevations detected, because I won't be testing for it. I suspect that CPK elevations come from people being more physically active when their skin clears up.

I have the sense that our comfort with Janus kinase (JAK) inhibition will grow rapidly as we use the drug for patients with vitiligo, alopecia areata, resistant atopic dermatitis, and other diseases. Many of us are comfortable with methotrexate, dapsone, cyclosporine, and mycophenolate; our comfort with JAK inhibitors for our patients who need it will almost surely follow.

Williams and colleagues did a meta-analysis looking at the relationship between AD and rheumatoid arthritis (RA). They claim that “patients with AD had significantly increased odds of comorbid RA.” This claim should not be taken at face value. What they found was that the observed rate of RA was higher in patients with AD than in controls, and the difference was not something you would see by chance very often. But that does not make something significant. To truly be significant, you'd expect it to be clinically meaningful. The relationship they found — even if not due to chance or to some unmeasured bias — wasn't clinically relevant, in my opinion. RA is a relatively rare phenomenon. If it is barely more common in patients with AD than in controls, it is still rare in AD patients. We don't need to screen for RA in AD patients. We don't need to do anything with this apparent association.

The bottom line is to be wary when you see an article that reports a “significant” finding, especially when it is based on a higher relative risk, like an odds ratio. What we need to know is what the absolute magnitude of the risk is. We need to know how many patients with AD you'd have to see before you'd see one more case of RA due to AD. Williams and colleagues' study doesn't report the information we need as clinicians.

Fijan and colleagues did a meta-analysis to assess the effects of single-strain probiotic lactobacilli on atopic dermatitis. The found a “significant” (meaning, statistically significant) reduction with the lactobacilli treatment compared with placebo. They used the SCORing Atopic Dermatitis (SCORAD) index as the outcome. There was a mean 4.5-unit improvement.

For comparison, Wollenberg and colleagues¹ reported the SCORAD improvement seen with dupilumab: 49- and 46-unit improvements in children and adolescents, respectively.

While I'm sure that patients would love a safe, effective, “all natural” probiotic option for atopic dermatitis, I'm not optimistic that this gut magic is going to work.

Additional Reference

1. Wollenberg A, Marcoux D, Silverberg JI, et al. Dupilumab provides rapid and sustained improvement in SCORing Atopic Dermatitis outcomes in paediatric patients with atopic dermatitis. Acta Derm Venereol. 2022;102:adv00726. doi: 10.2340/actadv.v102.854

The most common adverse events were acne, headache, upper respiratory tract infection, creatine phosphokinase (CPK) level elevations, and nasopharyngitis. I'm confident that none of my patients will have CPK elevations detected, because I won't be testing for it. I suspect that CPK elevations come from people being more physically active when their skin clears up.

I have the sense that our comfort with Janus kinase (JAK) inhibition will grow rapidly as we use the drug for patients with vitiligo, alopecia areata, resistant atopic dermatitis, and other diseases. Many of us are comfortable with methotrexate, dapsone, cyclosporine, and mycophenolate; our comfort with JAK inhibitors for our patients who need it will almost surely follow.

Williams and colleagues did a meta-analysis looking at the relationship between AD and rheumatoid arthritis (RA). They claim that “patients with AD had significantly increased odds of comorbid RA.” This claim should not be taken at face value. What they found was that the observed rate of RA was higher in patients with AD than in controls, and the difference was not something you would see by chance very often. But that does not make something significant. To truly be significant, you'd expect it to be clinically meaningful. The relationship they found — even if not due to chance or to some unmeasured bias — wasn't clinically relevant, in my opinion. RA is a relatively rare phenomenon. If it is barely more common in patients with AD than in controls, it is still rare in AD patients. We don't need to screen for RA in AD patients. We don't need to do anything with this apparent association.

The bottom line is to be wary when you see an article that reports a “significant” finding, especially when it is based on a higher relative risk, like an odds ratio. What we need to know is what the absolute magnitude of the risk is. We need to know how many patients with AD you'd have to see before you'd see one more case of RA due to AD. Williams and colleagues' study doesn't report the information we need as clinicians.

Fijan and colleagues did a meta-analysis to assess the effects of single-strain probiotic lactobacilli on atopic dermatitis. The found a “significant” (meaning, statistically significant) reduction with the lactobacilli treatment compared with placebo. They used the SCORing Atopic Dermatitis (SCORAD) index as the outcome. There was a mean 4.5-unit improvement.

For comparison, Wollenberg and colleagues¹ reported the SCORAD improvement seen with dupilumab: 49- and 46-unit improvements in children and adolescents, respectively.

While I'm sure that patients would love a safe, effective, “all natural” probiotic option for atopic dermatitis, I'm not optimistic that this gut magic is going to work.

Additional Reference

1. Wollenberg A, Marcoux D, Silverberg JI, et al. Dupilumab provides rapid and sustained improvement in SCORing Atopic Dermatitis outcomes in paediatric patients with atopic dermatitis. Acta Derm Venereol. 2022;102:adv00726. doi: 10.2340/actadv.v102.854

The most common adverse events were acne, headache, upper respiratory tract infection, creatine phosphokinase (CPK) level elevations, and nasopharyngitis. I'm confident that none of my patients will have CPK elevations detected, because I won't be testing for it. I suspect that CPK elevations come from people being more physically active when their skin clears up.

I have the sense that our comfort with Janus kinase (JAK) inhibition will grow rapidly as we use the drug for patients with vitiligo, alopecia areata, resistant atopic dermatitis, and other diseases. Many of us are comfortable with methotrexate, dapsone, cyclosporine, and mycophenolate; our comfort with JAK inhibitors for our patients who need it will almost surely follow.

Williams and colleagues did a meta-analysis looking at the relationship between AD and rheumatoid arthritis (RA). They claim that “patients with AD had significantly increased odds of comorbid RA.” This claim should not be taken at face value. What they found was that the observed rate of RA was higher in patients with AD than in controls, and the difference was not something you would see by chance very often. But that does not make something significant. To truly be significant, you'd expect it to be clinically meaningful. The relationship they found — even if not due to chance or to some unmeasured bias — wasn't clinically relevant, in my opinion. RA is a relatively rare phenomenon. If it is barely more common in patients with AD than in controls, it is still rare in AD patients. We don't need to screen for RA in AD patients. We don't need to do anything with this apparent association.

The bottom line is to be wary when you see an article that reports a “significant” finding, especially when it is based on a higher relative risk, like an odds ratio. What we need to know is what the absolute magnitude of the risk is. We need to know how many patients with AD you'd have to see before you'd see one more case of RA due to AD. Williams and colleagues' study doesn't report the information we need as clinicians.

Fijan and colleagues did a meta-analysis to assess the effects of single-strain probiotic lactobacilli on atopic dermatitis. The found a “significant” (meaning, statistically significant) reduction with the lactobacilli treatment compared with placebo. They used the SCORing Atopic Dermatitis (SCORAD) index as the outcome. There was a mean 4.5-unit improvement.

For comparison, Wollenberg and colleagues¹ reported the SCORAD improvement seen with dupilumab: 49- and 46-unit improvements in children and adolescents, respectively.

While I'm sure that patients would love a safe, effective, “all natural” probiotic option for atopic dermatitis, I'm not optimistic that this gut magic is going to work.

Additional Reference

1. Wollenberg A, Marcoux D, Silverberg JI, et al. Dupilumab provides rapid and sustained improvement in SCORing Atopic Dermatitis outcomes in paediatric patients with atopic dermatitis. Acta Derm Venereol. 2022;102:adv00726. doi: 10.2340/actadv.v102.854

MUNICH – Adding carotid revascularization to optimized medical therapy (OMT) does not appear to offer a clinical benefit in patients with significant carotid stenosis and a low to intermediate 5-year risk of stroke, suggests a planned interim analysis of ECST-2.

Almost 430 patients with symptomatic and asymptomatic atherosclerotic carotid stenosis greater than or equal to 50% and a Carotid Artery Risk (CAR) score less than 20% were randomly assigned to OMT alone or OMT plus revascularization with carotid endarterectomy (CEA) or carotid artery stenting.

The study, which was presented at the annual European Stroke Organisation Conference, was stopped early because of slow recruitment.

Nevertheless, the current results showed that there was no significant difference at 2 years between the treatment groups in the rate of a composite endpoint, as well as the occurrence of any stroke, myocardial infarction, and periprocedural death.

In other words, “there was no evidence of benefit at 2 years from additional carotid revascularization” in patients with carotid stenosis who had a low to intermediate predicted stroke risk, said study presenter Paul Nederkoorn, MD, PhD, department of neurology, Amsterdam UMC, University of Amsterdam.

He added, however, that the complete 2 years will include additional analyses, including an analysis of silent infarcts on MRI, which may affect the results, and that longer clinical follow-up is required.

Future work will include the design and validation of a novel stroke risk prediction tool that will include MRI plaque imaging and will allow individualized patient selection for revascularization, as well as a cost-effectiveness analysis, he noted.
 

Conclusions ‘difficult’

Session co-chair Peter Kelly, MD, professor of neurology at Mater University Hospital/University College Dublin, and president-elect of the European Stroke Association, described the findings as “interesting” and that it was “great to see them.”

“I’m sure we’ll be discussing these results for a while,” he added.

But co-chair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the Stroke Unit, department of neurology, Oslo University Hospital, said that it’s “difficult to draw firm conclusions from the trial.”

The patients were highly selected, recruitment was “perhaps a bit too slow,” and the study was probably conducted over too many sites, she said in an interview.

Dr. Sandset also noted that the options available for OMT have changed over the course of the study, as well as the overall approach to management.

“We are more aware of how we should treat” these patients, and “we’re probably a bit more aggressive,” which will have shifted the outcomes in the comparator arm as the study progressed.

“That is the challenge of doing these trials that take many years to run – our practice changes.”
 

‘Old evidence’

In his presentation, Dr. Nederkoorn pointed out that, while the current guidelines for CEA are “robust,” they are based on “old evidence” from trials conducted 20-30 years ago.

During that time, he said, medical treatment has improved significantly, and the risk for stroke has approximately halved. Yet the decision to perform CEA is still largely based on the degree of stenosis and the patient’s symptom status.

Dr. Nederkoorn suggested, however, that factors such as plaque ulceration and patient characteristics and comorbidities might influence the risk-benefit ratio for revascularization.

The current trial was therefore established to test the hypothesis that patients with carotid stenosis greater than or equal to 50% and a low to intermediate risk of stroke will not benefit from additional carotid revascularization on top of optimized medical therapy.

The team conducted a prospective, multicenter, open clinical trial in which patients with both symptomatic and asymptomatic atherosclerotic carotid stenosis were randomly assigned to revascularization plus OMT or OMT alone.

Dr. Nederkoorn explained that a low to intermediate 5-year risk for stroke was established using the CAR score less than 20%.

This is based on a range of parameters, including the sex and age of the patient, degree of stenosis, the type of and time since the event, and the presence of comorbidities, among other factors.

He said that the data was originally derived from the NASCET trial, which was published in 1998, and the first ECST trial, published in the same year.

Since then, the risk of ipsilateral stroke has “strongly declined,” Dr. Nederkoorn said, and so the CAR score was recalibrated to reflect the likely benefit of current OMT.

For the trial, OMT included antihypertensive and cholesterol-lowering medications, and dietary changes, alongside antiplatelet agents and anticoagulation, if indicated, to achieve predefined, guideline-led lipid and blood pressure targets.

Revascularization included CEA and coronary artery stenting in selected patients and was recommended to be performed within 2 weeks of randomization in symptomatic patients and within 4 weeks in asymptomatic patients.

When the trial started in 2012, the intention was to recruit 2,000 patients, with a planned interim analysis after enrollment of 320 patients.

However, recruitment was suspended in 2019, with 429 patients having been enrolled, as it was clear that achieving a cohort of 2,000 patients was “not practical without a change in the trial design” to include MRI plaque imaging and without further funding.

Dr. Nederkoorn showed that the baseline characteristics of the OMT and revascularization plus OMT groups were comparable. The average age of the patients in the groups was 71-72 years, and 31% were female.

Symptomatic disease was present in about 40% of patients, and about 76% had hypertension. Type 2 diabetes was reported in roughly one-quarter of the patients.

There was no difference in the time from randomization to the revascularization procedure between patients with asymptomatic and symptomatic disease.

Moving to the primary outcome, which was a composite of periprocedural death within 90 days of randomization and clinically manifest stroke or myocardial infarction at 2 years, Dr. Nederkoorn showed that there was no significant difference between the treatment groups.

Despite a suggestion that patients undergoing revascularization experienced “more harm” in the initial follow-up period, particularly in patients with a CAR score greater than 10%, the event curves met at around 18 months.

Overall, the hazard ratio between revascularization plus OMT versus OMT alone was 0.96 (95% confidence interval, 0.53-1.76, P = .90).

Breaking down the composite endpoint, there was a numerically lower rate of any stroke with OMT alone, compared with revascularization plus OMT over the study period, but again the difference was not significant at 2 years, at a hazard ratio of 0.68 (95% CI, 0.32-1.42, P = .30).

There was only one case of periprocedural death, in the revascularization arm. Although myocardial infarction was numerically twice as likely with OMT alone, compared with the combined intervention arm, the difference was not significant, at a hazard ratio of 2.00 (95% CI, 0.68-5.84, P = .21).

The study was funded by the National Institute for Health and Care Research, the Swiss National Science Foundation, The Netherlands Organisation of Scientific Research, and the Leeds Neurology Foundation. No relevant financial relationships were declared.

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

MUNICH – Adding carotid revascularization to optimized medical therapy (OMT) does not appear to offer a clinical benefit in patients with significant carotid stenosis and a low to intermediate 5-year risk of stroke, suggests a planned interim analysis of ECST-2.

Almost 430 patients with symptomatic and asymptomatic atherosclerotic carotid stenosis greater than or equal to 50% and a Carotid Artery Risk (CAR) score less than 20% were randomly assigned to OMT alone or OMT plus revascularization with carotid endarterectomy (CEA) or carotid artery stenting.

The study, which was presented at the annual European Stroke Organisation Conference, was stopped early because of slow recruitment.

Nevertheless, the current results showed that there was no significant difference at 2 years between the treatment groups in the rate of a composite endpoint, as well as the occurrence of any stroke, myocardial infarction, and periprocedural death.

In other words, “there was no evidence of benefit at 2 years from additional carotid revascularization” in patients with carotid stenosis who had a low to intermediate predicted stroke risk, said study presenter Paul Nederkoorn, MD, PhD, department of neurology, Amsterdam UMC, University of Amsterdam.

He added, however, that the complete 2 years will include additional analyses, including an analysis of silent infarcts on MRI, which may affect the results, and that longer clinical follow-up is required.

Future work will include the design and validation of a novel stroke risk prediction tool that will include MRI plaque imaging and will allow individualized patient selection for revascularization, as well as a cost-effectiveness analysis, he noted.
 

Conclusions ‘difficult’

Session co-chair Peter Kelly, MD, professor of neurology at Mater University Hospital/University College Dublin, and president-elect of the European Stroke Association, described the findings as “interesting” and that it was “great to see them.”

“I’m sure we’ll be discussing these results for a while,” he added.

But co-chair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the Stroke Unit, department of neurology, Oslo University Hospital, said that it’s “difficult to draw firm conclusions from the trial.”

The patients were highly selected, recruitment was “perhaps a bit too slow,” and the study was probably conducted over too many sites, she said in an interview.

Dr. Sandset also noted that the options available for OMT have changed over the course of the study, as well as the overall approach to management.

“We are more aware of how we should treat” these patients, and “we’re probably a bit more aggressive,” which will have shifted the outcomes in the comparator arm as the study progressed.

“That is the challenge of doing these trials that take many years to run – our practice changes.”
 

‘Old evidence’

In his presentation, Dr. Nederkoorn pointed out that, while the current guidelines for CEA are “robust,” they are based on “old evidence” from trials conducted 20-30 years ago.

During that time, he said, medical treatment has improved significantly, and the risk for stroke has approximately halved. Yet the decision to perform CEA is still largely based on the degree of stenosis and the patient’s symptom status.

Dr. Nederkoorn suggested, however, that factors such as plaque ulceration and patient characteristics and comorbidities might influence the risk-benefit ratio for revascularization.

The current trial was therefore established to test the hypothesis that patients with carotid stenosis greater than or equal to 50% and a low to intermediate risk of stroke will not benefit from additional carotid revascularization on top of optimized medical therapy.

The team conducted a prospective, multicenter, open clinical trial in which patients with both symptomatic and asymptomatic atherosclerotic carotid stenosis were randomly assigned to revascularization plus OMT or OMT alone.

Dr. Nederkoorn explained that a low to intermediate 5-year risk for stroke was established using the CAR score less than 20%.

This is based on a range of parameters, including the sex and age of the patient, degree of stenosis, the type of and time since the event, and the presence of comorbidities, among other factors.

He said that the data was originally derived from the NASCET trial, which was published in 1998, and the first ECST trial, published in the same year.

Since then, the risk of ipsilateral stroke has “strongly declined,” Dr. Nederkoorn said, and so the CAR score was recalibrated to reflect the likely benefit of current OMT.

For the trial, OMT included antihypertensive and cholesterol-lowering medications, and dietary changes, alongside antiplatelet agents and anticoagulation, if indicated, to achieve predefined, guideline-led lipid and blood pressure targets.

Revascularization included CEA and coronary artery stenting in selected patients and was recommended to be performed within 2 weeks of randomization in symptomatic patients and within 4 weeks in asymptomatic patients.

When the trial started in 2012, the intention was to recruit 2,000 patients, with a planned interim analysis after enrollment of 320 patients.

However, recruitment was suspended in 2019, with 429 patients having been enrolled, as it was clear that achieving a cohort of 2,000 patients was “not practical without a change in the trial design” to include MRI plaque imaging and without further funding.

Dr. Nederkoorn showed that the baseline characteristics of the OMT and revascularization plus OMT groups were comparable. The average age of the patients in the groups was 71-72 years, and 31% were female.

Symptomatic disease was present in about 40% of patients, and about 76% had hypertension. Type 2 diabetes was reported in roughly one-quarter of the patients.

There was no difference in the time from randomization to the revascularization procedure between patients with asymptomatic and symptomatic disease.

Moving to the primary outcome, which was a composite of periprocedural death within 90 days of randomization and clinically manifest stroke or myocardial infarction at 2 years, Dr. Nederkoorn showed that there was no significant difference between the treatment groups.

Despite a suggestion that patients undergoing revascularization experienced “more harm” in the initial follow-up period, particularly in patients with a CAR score greater than 10%, the event curves met at around 18 months.

Overall, the hazard ratio between revascularization plus OMT versus OMT alone was 0.96 (95% confidence interval, 0.53-1.76, P = .90).

Breaking down the composite endpoint, there was a numerically lower rate of any stroke with OMT alone, compared with revascularization plus OMT over the study period, but again the difference was not significant at 2 years, at a hazard ratio of 0.68 (95% CI, 0.32-1.42, P = .30).

There was only one case of periprocedural death, in the revascularization arm. Although myocardial infarction was numerically twice as likely with OMT alone, compared with the combined intervention arm, the difference was not significant, at a hazard ratio of 2.00 (95% CI, 0.68-5.84, P = .21).

The study was funded by the National Institute for Health and Care Research, the Swiss National Science Foundation, The Netherlands Organisation of Scientific Research, and the Leeds Neurology Foundation. No relevant financial relationships were declared.

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

MUNICH – Adding carotid revascularization to optimized medical therapy (OMT) does not appear to offer a clinical benefit in patients with significant carotid stenosis and a low to intermediate 5-year risk of stroke, suggests a planned interim analysis of ECST-2.

Almost 430 patients with symptomatic and asymptomatic atherosclerotic carotid stenosis greater than or equal to 50% and a Carotid Artery Risk (CAR) score less than 20% were randomly assigned to OMT alone or OMT plus revascularization with carotid endarterectomy (CEA) or carotid artery stenting.

The study, which was presented at the annual European Stroke Organisation Conference, was stopped early because of slow recruitment.

Nevertheless, the current results showed that there was no significant difference at 2 years between the treatment groups in the rate of a composite endpoint, as well as the occurrence of any stroke, myocardial infarction, and periprocedural death.

In other words, “there was no evidence of benefit at 2 years from additional carotid revascularization” in patients with carotid stenosis who had a low to intermediate predicted stroke risk, said study presenter Paul Nederkoorn, MD, PhD, department of neurology, Amsterdam UMC, University of Amsterdam.

He added, however, that the complete 2 years will include additional analyses, including an analysis of silent infarcts on MRI, which may affect the results, and that longer clinical follow-up is required.

Future work will include the design and validation of a novel stroke risk prediction tool that will include MRI plaque imaging and will allow individualized patient selection for revascularization, as well as a cost-effectiveness analysis, he noted.
 

Conclusions ‘difficult’

Session co-chair Peter Kelly, MD, professor of neurology at Mater University Hospital/University College Dublin, and president-elect of the European Stroke Association, described the findings as “interesting” and that it was “great to see them.”

“I’m sure we’ll be discussing these results for a while,” he added.

But co-chair Else Charlotte Sandset, MD, PhD, a consultant neurologist in the Stroke Unit, department of neurology, Oslo University Hospital, said that it’s “difficult to draw firm conclusions from the trial.”

The patients were highly selected, recruitment was “perhaps a bit too slow,” and the study was probably conducted over too many sites, she said in an interview.

Dr. Sandset also noted that the options available for OMT have changed over the course of the study, as well as the overall approach to management.

“We are more aware of how we should treat” these patients, and “we’re probably a bit more aggressive,” which will have shifted the outcomes in the comparator arm as the study progressed.

“That is the challenge of doing these trials that take many years to run – our practice changes.”
 

‘Old evidence’

In his presentation, Dr. Nederkoorn pointed out that, while the current guidelines for CEA are “robust,” they are based on “old evidence” from trials conducted 20-30 years ago.

During that time, he said, medical treatment has improved significantly, and the risk for stroke has approximately halved. Yet the decision to perform CEA is still largely based on the degree of stenosis and the patient’s symptom status.

Dr. Nederkoorn suggested, however, that factors such as plaque ulceration and patient characteristics and comorbidities might influence the risk-benefit ratio for revascularization.

The current trial was therefore established to test the hypothesis that patients with carotid stenosis greater than or equal to 50% and a low to intermediate risk of stroke will not benefit from additional carotid revascularization on top of optimized medical therapy.

The team conducted a prospective, multicenter, open clinical trial in which patients with both symptomatic and asymptomatic atherosclerotic carotid stenosis were randomly assigned to revascularization plus OMT or OMT alone.

Dr. Nederkoorn explained that a low to intermediate 5-year risk for stroke was established using the CAR score less than 20%.

This is based on a range of parameters, including the sex and age of the patient, degree of stenosis, the type of and time since the event, and the presence of comorbidities, among other factors.

He said that the data was originally derived from the NASCET trial, which was published in 1998, and the first ECST trial, published in the same year.

Since then, the risk of ipsilateral stroke has “strongly declined,” Dr. Nederkoorn said, and so the CAR score was recalibrated to reflect the likely benefit of current OMT.

For the trial, OMT included antihypertensive and cholesterol-lowering medications, and dietary changes, alongside antiplatelet agents and anticoagulation, if indicated, to achieve predefined, guideline-led lipid and blood pressure targets.

Revascularization included CEA and coronary artery stenting in selected patients and was recommended to be performed within 2 weeks of randomization in symptomatic patients and within 4 weeks in asymptomatic patients.

When the trial started in 2012, the intention was to recruit 2,000 patients, with a planned interim analysis after enrollment of 320 patients.

However, recruitment was suspended in 2019, with 429 patients having been enrolled, as it was clear that achieving a cohort of 2,000 patients was “not practical without a change in the trial design” to include MRI plaque imaging and without further funding.

Dr. Nederkoorn showed that the baseline characteristics of the OMT and revascularization plus OMT groups were comparable. The average age of the patients in the groups was 71-72 years, and 31% were female.

Symptomatic disease was present in about 40% of patients, and about 76% had hypertension. Type 2 diabetes was reported in roughly one-quarter of the patients.

There was no difference in the time from randomization to the revascularization procedure between patients with asymptomatic and symptomatic disease.

Moving to the primary outcome, which was a composite of periprocedural death within 90 days of randomization and clinically manifest stroke or myocardial infarction at 2 years, Dr. Nederkoorn showed that there was no significant difference between the treatment groups.

Despite a suggestion that patients undergoing revascularization experienced “more harm” in the initial follow-up period, particularly in patients with a CAR score greater than 10%, the event curves met at around 18 months.

Overall, the hazard ratio between revascularization plus OMT versus OMT alone was 0.96 (95% confidence interval, 0.53-1.76, P = .90).

Breaking down the composite endpoint, there was a numerically lower rate of any stroke with OMT alone, compared with revascularization plus OMT over the study period, but again the difference was not significant at 2 years, at a hazard ratio of 0.68 (95% CI, 0.32-1.42, P = .30).

There was only one case of periprocedural death, in the revascularization arm. Although myocardial infarction was numerically twice as likely with OMT alone, compared with the combined intervention arm, the difference was not significant, at a hazard ratio of 2.00 (95% CI, 0.68-5.84, P = .21).

The study was funded by the National Institute for Health and Care Research, the Swiss National Science Foundation, The Netherlands Organisation of Scientific Research, and the Leeds Neurology Foundation. No relevant financial relationships were declared.

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