Stroke

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

The European Medicines Agency continues to reassure the public about the safety of the AstraZeneca COVID-19 vaccine, although several countries have imposed new restrictions on the product, owing to its link to a rare clotting disorder.

Use of the vaccine has been suspended for individuals younger than 55 or 60 years in several European countries and in Canada after reports of a prothrombotic disorder and thrombocytopenia, mainly in younger individuals.

Now, more information on the prothrombotic disorder has become available. The vaccine appears to be linked to a condition that clinically resembles heparin-induced thrombocytopenia (HIT) and that occurs mainly in younger women.

Researchers have described clinical and laboratory details of nine patients from Germany and Austria who developed this condition 4-16 days after receiving the AstraZeneca vaccine in a preprint article published March 28, 2021, on Research Square.

They found that serum from four patients who were tested showed platelet-activating antibodies directed against platelet factor 4 (PF4), similar to what is seen in HIT.

They are proposing naming the condition “vaccine-induced prothrombotic immune thrombocytopenia (VIPIT)” to avoid confusion with HIT.

At a press conference March 31, the EMA said its ongoing review of the situation “has not identified any specific risk factors, such as age, gender, or a previous medical history of clotting disorders, for these very rare events. A causal link with the vaccine is not proven but is possible, and further analysis is continuing.”

A statement from the agency noted: “EMA is of the view that the benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects.”

But it added: “Vaccinated people should be aware of the remote possibility of these very rare types of blood clots occurring. If they have symptoms suggestive of clotting problems as described in the product information, they should seek immediate medical attention and inform health care professionals of their recent vaccination.”
 

VIPIT study

In the Research Square preprint article, a group led by Andreas Greinacher, MD, professor of transfusion medicine at the Greifswald (Germany) University Clinic, reported on clinical and laboratory features of nine patients (eight of whom were women) in Germany and Austria who developed thrombosis and thrombocytopenia after they received the AstraZeneca vaccine.

The researchers explained that they investigated whether these patients could have a prothrombotic disorder caused by platelet-activating antibodies directed against PF4, which is known to be caused by heparin and sometimes environmental triggers.

The nine patients were aged 22-49 years and presented with thrombosis beginning 4-16 days post vaccination. Seven patients had cerebral venous thrombosis (CVT), one had pulmonary embolism, and one had splanchnic vein thrombosis and CVT. Four patients died. None had received heparin prior to symptom onset.

Serum from four patients was tested for anti-PF4/heparin antibodies, and all four tested strongly positive. All four also tested strongly positive on platelet activation assay for the presence of PF4 independently of heparin.

The authors noted that it has been recognized that triggers other than heparin, including some infections, can rarely cause a disorder that strongly resembles HIT. These cases have been referred to as spontaneous HIT syndrome.

They said that their current findings have several important clinical implications.

“Clinicians should be aware that onset of (venous or arterial) thrombosis particularly at unusual sites such as in the brain or abdomen and thrombocytopenia beginning approximately 5-14 days after vaccination can represent a rare adverse effect of preceding COVID-19 vaccination,” they wrote. To date, this has only been reported with the AstraZeneca vaccine.

They pointed out that enzyme immunoassays for HIT are widely available and can be used to investigate for potential postvaccination anti-PF4 antibody–associated thrombocytopenia/thrombosis. For such patients, referral should be made to a laboratory that performs platelet-activation assays.

Although this syndrome differs from typical HIT, the researchers noted that at least one patient showed strong platelet activation in the presence of heparin. They thus recommended therapy with nonheparin anticoagulants, such as the direct oral anticoagulants.

They also wrote that high-dose intravenous immunoglobulin has been shown to be effective for treating severe HIT and could also be an important treatment adjunct for patients who develop life-threatening thrombotic events, such as cerebral vein sinus thrombosis (CVST), after being vaccinated.
 

EMA data to date

Updated data, reported at the EMA press briefing on March 31, indicate that 62 cases of CVST have been reported worldwide (44 from the European Union). These data may not yet include all the German cases.

Peter Arlett, MD, head of pharmacovigilance and epidemiology at the EMA, said there were more cases than expected in the 2-week window after vaccination among patients younger than 60 and that health care professionals should be alert to features of this condition, including headache and blurred vision.

He suggested that the higher rate of the condition among younger women may reflect the population that received this vaccine, because initially, the vaccine was not recommended for older people in many countries and was targeted toward younger health care workers, who were mainly women.

The German regulatory agency, the Paul Ehrlich Institute, reported this week that it has now registered 31 cases of CVST among nearly 2.7 million people who had received the vaccine in Germany. Of these patients, 19 also were found to have a deficiency of blood platelets or thrombocytopenia. Nine of the affected patients died. All but two of the cases occurred in women aged 20-63 years. The two men were aged 36 and 57 years.

These data have prompted the German authorities to limit use of the AstraZeneca vaccine to those aged 60 years and older. Even before this decision, senior clinicians in Germany had been urging a change in the vaccination recommendations.

For example, Bernd Salzberger, MD, head of infectious diseases, University Hospital Regensburg (Germany), told the Science Media Center: “In women, a complicated course of COVID disease is less common from the start and is so rare in younger women that the chance of avoiding a fatal course through vaccination in women without comorbidities is of the same order of magnitude as the risk of this rare side effect.”

Sandra Ciesek, MD, a virologist at Goethe University, Frankfurt, Germany, told the journal Science: “The argument I keep hearing is that the risk-benefit ratio is still positive. But we do not have just one vaccine, we have several. So, restricting the AstraZeneca vaccine to older people makes sense to me, and it does not waste any doses.”
 

Concerns put in perspective

Commenting of the latest developments, thrombosis expert Saskia Middeldorp, MD, head of internal medicine at Radboud University Medical Center, Nijmegen, the Netherlands, said it was vitally important that these concerns be put in perspective and that the vaccination program with the AstraZeneca product continue.

“There are some concerning reports about very rare blood clotting disorders and low platelet counts possibly associated with the AstraZeneca vaccine. Groups from Germany and Norway have identified a syndrome similar to HIT, which seems to explain the cause of this very rare side effect,” Dr. Middeldorp noted.

“But with such a high pressure from the virus and many countries now going into a third wave of infection, anything that might slow down vaccination rates will cause much more harm than good,” she warned.

Dr. Middeldorp believes the incidence of this HIT-type syndrome linked to the vaccine is about 1-2 per million. “These are estimates based on the number of reports of this side effect and denominators from the U.K. and EU populations,” she explained. However, Germany has restricted the vaccine on the basis of German data, which appear to show higher rates of the condition. It is not known why the rates are higher in Germany.

“The European Medicines Agency is looking at this very closely. Their statement is quite clear. There is no foundation for changing policy on vaccination,” Dr. Middeldorp stated.

She cautioned that these reports were reducing confidence in the AstraZeneca vaccine, particularly among young people, which she said was causing “a major setback” for the vaccination program.

Noting that everything must be viewed in the context of this severe pandemic, Dr. Middeldorp emphasized that the benefit of the vaccine outweighed any risk, even among young people.

“To those who may be hesitating to have the vaccine as they don’t think they are at high risk of severe COVID infection, I would say there are a lot of young people in the ICU at present with COVID, and your chance of a severe COVID illness is far higher than the 1 or 2 in a million risk of a severe reaction to the vaccine,” she stated.

Dr. Greinacher has received grants and nonfinancial support from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Bristol-Myers Squibb, Paringenix, Bayer Healthcare, Gore, Rovi, Sagent, and Biomarin/Prosensa; personal fees from Aspen, Boehringer Ingelheim, Merck Sharp & Dohme, Macopharma, Bristol-Myers Squibb, Chromatec, and Instrumentation Laboratory; and nonfinancial support from Boehringer Ingelheim, Portola, Ergomed, and GTH outside the submitted work.

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

The evidence in favor of endovascular therapy for selected stroke patients who present in the late time window, from 6 to 24 hours after stroke onset, has been strengthened by the results of a new meta-analysis of data from six clinical trials.

Results of the AURORA analysis showed that for every 100 patients treated with thrombectomy, 33 patients will have less disability, and 27 patients will achieve an independent level of functioning compared with patients who receive only standard medical care.

The benefit of mechanical removal of the clot for selected patients who may have salvageable brain tissue, as identified through the use of various imaging modalities, was maintained whether the patient had a “wake-up stroke” or the onset of symptoms was witnessed, regardless of the point in time within the late window. In fact, the benefit of intervention was greater for patients who presented in the latter part of the late time window.

Never too late for urgent medical care

“While the findings of this analysis do not contradict the mantra that the earlier treatment is instituted, the higher the chance of a good outcome, they highlight the fact that it is never too late to seek urgent medical care,” said lead investigator Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey.

“The implications of the findings from AURORA are that they could lead to a change in guidelines from endorsement of thrombectomy as level 1a recommendation in eligible patients presenting in the 6- to 16-hour time window to a 6- to 24-hour time window,” said Dr. Jovin.

“Furthermore, there are strong signals of benefit of thrombectomy in patients who are not selected based on volumetric analysis of baseline infarct (core) or extent of tissue at risk (penumbra), such that when those imaging modalities are not available or contraindicated, selection based on noncontrast CT and clinical information only may be acceptable,” he added. “Finally, the possibility of benefit from thrombectomy performed beyond 24 hours from last seen well is real and should be explored in future studies.”

The AURORA findings were presented at the virtual International Stroke Conference (ISC) 2021.

The objective of the study was to provide a more precise estimate of the benefit of thrombectomy for patients with stroke when performed within 6-24 hours after the patient was last seen well, Dr. Jovin explained.

He said the 6-hour cutoff was chosen somewhat arbitrarily, but added, “It is highly consequential, as it marks the point of demarcation between the early and late time window, and virtually all guidelines recommend different approaches, dependent on whether patients present before or after 6 hours from symptom onset.”

The 6+ hour window

Dr. Jovin pointed out that for patients who present beyond 6 hours, treatment options are more restricted, because the data on thrombectomy in this later period come mainly from two North American trials (DEFUSE 3 and DAWN) that had very stringent imaging criteria for enrollment.

“We wanted to create a heterogeneous dataset with regard to geography and selection criteria by forming the AURORA collaboration,” he commented. Their study involved an individual-level pooled analysis of all patients who underwent randomization after 6 hours from the time that they were last seen well. Patients were randomly assigned to receive either best medical therapy alone or best medical therapy plus thrombectomy (either with stent retrievers or aspiration) for anterior circulation proximal large-vessel occlusion stroke.

The data came from six trials: DAWN (which enrolled patients 6-24 hours from stroke onset), DEFUSE 3 (6-16 hours), ESCAPE (0-12 hours), REVASCAT (0-8 hours), RESILIENT (0-8 hours), and POSITIVE (0-12 hours). In total, 505 patients were included in the meta-analysis, 266 in the intervention group, and 239 in the control group.

“By pooling data on patients presenting after 6 hours from all these trails, we achieve greater precision for treatment effect estimation and increased the power for subgroup analysis,” Dr. Jovin noted.

Although the majority of the patients were in the DAWN and DIFFUSE 3 trials (n = 388), “there are still a good number from the other four trials (n = 117),” Dr. Jovin reported.

Most of the trials used Modified Rankin Scale (mRS) ordinal or shift analysis as their primary endpoint, which was the also the endpoint chosen for this meta-analysis.

Imaging selection criteria ranged from fully automated software-generated quantitative volumetric analysis of baseline infarct (core) or tissue at risk to CT perfusion and plain CT/CTA. The minimum ASPECTS score was 5 or 6.

There were no imbalances in baseline characteristics. The median NIH Stroke Scale score was 16, and the median ASPECTS score was 8. The median time to randomization was 10.5 hours.

With regard to safety, there was no significant difference in rates of symptomatic intracerebral hemorrhage (5.3% in the intervention group vs. 3.3% in the control group; P = .23) or in mortality at 90 days (16.5% vs. 19.3%; P = .87). Jovin noted that these results are very similar to those from the HERMES meta-analysis of patients treated in the early time window.

The primary outcome – ordinal analysis of the mRS distribution – showed an adjusted odds ratio of 2.54 (P < .0001) for benefit in the intervention group. The number needed to treat to reduce disability was 3. “This is again very similar to the HERMES meta-analysis of patients in the early window,” Dr. Jovin said.

The P value for heterogeneity of treatment effect across the six studies was nonsignificant.

Secondary outcome analysis showed an “almost 27%” difference in good functional outcome (MRS, 0-2) between the two groups (45.9% in the intervention group vs. 19.3% in the control group), which translates into a number needed to treat of 3.8, Dr. Jovin reported.

Subgroup analysis showed a treatment effect favoring intervention across all prespecified subgroup factors, including age, sex, occlusion location, mode of presentation (wake-up vs. witnessed), and ASPECTS score, with the caveat that most of the patients were enrolled with ASPECTS scores of 7 or greater.

Early versus late

Surprisingly, although thrombectomy was found to be beneficial in both the 6- to 12-hour and 12- to 24-hour time window, the magnitude of benefit was significantly higher in the later rather than the earlier time window. The odds ratio of a better outcome with thrombectomy on the mRS shift analysis in those presenting in the 6- to 12-hour period was 1.78, compared with 5.86 in the 12- to 24-hour time window.

“This should not be interpreted as a higher chance of a good outcome if treated late. In fact, the rate of good outcomes were numerically higher in the earlier treated patients, but the difference comes from the control group, which did much worse in patients randomized in the later time period,” Dr. Jovin said.

“Aurora was the goddess of dawn [in ancient Roman mythology], so this is a very fitting name, as it reminds us that we are in the dawn of a new era where patients are selected based on physiological data rather than on time, and we certainly hope that this work has brought us closer to this reality,” Dr. Jovin concluded.

Commenting on the study, Michael Hill, MD, University of Calgary (Alta.), said: “The work provides pooled empiric data to support the concept that time to treatment is no longer the sole threshold variable to be used in treatment decision-making. Instead, time is now simply another variable to consider in the context of clinical and imaging factors.”

Dr. Hill, who headed up the ESCAPE trial and was also involved in the current meta-analysis, added: “This meta-analysis supports the concept of patient selection using the ‘good scan’ model, rather than using a time-based concept of patient eligibility for endovascular therapy. It will further push changes in care, because the implication is that all patients with more severe acute stroke presentations need emergency neurovascular imaging to decide if they are eligible for treatment.”

The AURORA meta-analysis was funded by Stryker Neurovascular. Dr. Jovin reports stock holdings in Anaconda, Route 92, VizAi, FreeOx, Blockade Medical, Methinks, and Corindus; personal fees from Cerenovus and Contego Medical; travel support from Fundacio Ictus; and grant support from Medtronic and Stryker Neurovascular.

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

The evidence in favor of endovascular therapy for selected stroke patients who present in the late time window, from 6 to 24 hours after stroke onset, has been strengthened by the results of a new meta-analysis of data from six clinical trials.

Results of the AURORA analysis showed that for every 100 patients treated with thrombectomy, 33 patients will have less disability, and 27 patients will achieve an independent level of functioning compared with patients who receive only standard medical care.

The benefit of mechanical removal of the clot for selected patients who may have salvageable brain tissue, as identified through the use of various imaging modalities, was maintained whether the patient had a “wake-up stroke” or the onset of symptoms was witnessed, regardless of the point in time within the late window. In fact, the benefit of intervention was greater for patients who presented in the latter part of the late time window.

Never too late for urgent medical care

“While the findings of this analysis do not contradict the mantra that the earlier treatment is instituted, the higher the chance of a good outcome, they highlight the fact that it is never too late to seek urgent medical care,” said lead investigator Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey.

“The implications of the findings from AURORA are that they could lead to a change in guidelines from endorsement of thrombectomy as level 1a recommendation in eligible patients presenting in the 6- to 16-hour time window to a 6- to 24-hour time window,” said Dr. Jovin.

“Furthermore, there are strong signals of benefit of thrombectomy in patients who are not selected based on volumetric analysis of baseline infarct (core) or extent of tissue at risk (penumbra), such that when those imaging modalities are not available or contraindicated, selection based on noncontrast CT and clinical information only may be acceptable,” he added. “Finally, the possibility of benefit from thrombectomy performed beyond 24 hours from last seen well is real and should be explored in future studies.”

The AURORA findings were presented at the virtual International Stroke Conference (ISC) 2021.

The objective of the study was to provide a more precise estimate of the benefit of thrombectomy for patients with stroke when performed within 6-24 hours after the patient was last seen well, Dr. Jovin explained.

He said the 6-hour cutoff was chosen somewhat arbitrarily, but added, “It is highly consequential, as it marks the point of demarcation between the early and late time window, and virtually all guidelines recommend different approaches, dependent on whether patients present before or after 6 hours from symptom onset.”

The 6+ hour window

Dr. Jovin pointed out that for patients who present beyond 6 hours, treatment options are more restricted, because the data on thrombectomy in this later period come mainly from two North American trials (DEFUSE 3 and DAWN) that had very stringent imaging criteria for enrollment.

“We wanted to create a heterogeneous dataset with regard to geography and selection criteria by forming the AURORA collaboration,” he commented. Their study involved an individual-level pooled analysis of all patients who underwent randomization after 6 hours from the time that they were last seen well. Patients were randomly assigned to receive either best medical therapy alone or best medical therapy plus thrombectomy (either with stent retrievers or aspiration) for anterior circulation proximal large-vessel occlusion stroke.

The data came from six trials: DAWN (which enrolled patients 6-24 hours from stroke onset), DEFUSE 3 (6-16 hours), ESCAPE (0-12 hours), REVASCAT (0-8 hours), RESILIENT (0-8 hours), and POSITIVE (0-12 hours). In total, 505 patients were included in the meta-analysis, 266 in the intervention group, and 239 in the control group.

“By pooling data on patients presenting after 6 hours from all these trails, we achieve greater precision for treatment effect estimation and increased the power for subgroup analysis,” Dr. Jovin noted.

Although the majority of the patients were in the DAWN and DIFFUSE 3 trials (n = 388), “there are still a good number from the other four trials (n = 117),” Dr. Jovin reported.

Most of the trials used Modified Rankin Scale (mRS) ordinal or shift analysis as their primary endpoint, which was the also the endpoint chosen for this meta-analysis.

Imaging selection criteria ranged from fully automated software-generated quantitative volumetric analysis of baseline infarct (core) or tissue at risk to CT perfusion and plain CT/CTA. The minimum ASPECTS score was 5 or 6.

There were no imbalances in baseline characteristics. The median NIH Stroke Scale score was 16, and the median ASPECTS score was 8. The median time to randomization was 10.5 hours.

With regard to safety, there was no significant difference in rates of symptomatic intracerebral hemorrhage (5.3% in the intervention group vs. 3.3% in the control group; P = .23) or in mortality at 90 days (16.5% vs. 19.3%; P = .87). Jovin noted that these results are very similar to those from the HERMES meta-analysis of patients treated in the early time window.

The primary outcome – ordinal analysis of the mRS distribution – showed an adjusted odds ratio of 2.54 (P < .0001) for benefit in the intervention group. The number needed to treat to reduce disability was 3. “This is again very similar to the HERMES meta-analysis of patients in the early window,” Dr. Jovin said.

The P value for heterogeneity of treatment effect across the six studies was nonsignificant.

Secondary outcome analysis showed an “almost 27%” difference in good functional outcome (MRS, 0-2) between the two groups (45.9% in the intervention group vs. 19.3% in the control group), which translates into a number needed to treat of 3.8, Dr. Jovin reported.

Subgroup analysis showed a treatment effect favoring intervention across all prespecified subgroup factors, including age, sex, occlusion location, mode of presentation (wake-up vs. witnessed), and ASPECTS score, with the caveat that most of the patients were enrolled with ASPECTS scores of 7 or greater.

Early versus late

Surprisingly, although thrombectomy was found to be beneficial in both the 6- to 12-hour and 12- to 24-hour time window, the magnitude of benefit was significantly higher in the later rather than the earlier time window. The odds ratio of a better outcome with thrombectomy on the mRS shift analysis in those presenting in the 6- to 12-hour period was 1.78, compared with 5.86 in the 12- to 24-hour time window.

“This should not be interpreted as a higher chance of a good outcome if treated late. In fact, the rate of good outcomes were numerically higher in the earlier treated patients, but the difference comes from the control group, which did much worse in patients randomized in the later time period,” Dr. Jovin said.

“Aurora was the goddess of dawn [in ancient Roman mythology], so this is a very fitting name, as it reminds us that we are in the dawn of a new era where patients are selected based on physiological data rather than on time, and we certainly hope that this work has brought us closer to this reality,” Dr. Jovin concluded.

Commenting on the study, Michael Hill, MD, University of Calgary (Alta.), said: “The work provides pooled empiric data to support the concept that time to treatment is no longer the sole threshold variable to be used in treatment decision-making. Instead, time is now simply another variable to consider in the context of clinical and imaging factors.”

Dr. Hill, who headed up the ESCAPE trial and was also involved in the current meta-analysis, added: “This meta-analysis supports the concept of patient selection using the ‘good scan’ model, rather than using a time-based concept of patient eligibility for endovascular therapy. It will further push changes in care, because the implication is that all patients with more severe acute stroke presentations need emergency neurovascular imaging to decide if they are eligible for treatment.”

The AURORA meta-analysis was funded by Stryker Neurovascular. Dr. Jovin reports stock holdings in Anaconda, Route 92, VizAi, FreeOx, Blockade Medical, Methinks, and Corindus; personal fees from Cerenovus and Contego Medical; travel support from Fundacio Ictus; and grant support from Medtronic and Stryker Neurovascular.

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

The evidence in favor of endovascular therapy for selected stroke patients who present in the late time window, from 6 to 24 hours after stroke onset, has been strengthened by the results of a new meta-analysis of data from six clinical trials.

Results of the AURORA analysis showed that for every 100 patients treated with thrombectomy, 33 patients will have less disability, and 27 patients will achieve an independent level of functioning compared with patients who receive only standard medical care.

The benefit of mechanical removal of the clot for selected patients who may have salvageable brain tissue, as identified through the use of various imaging modalities, was maintained whether the patient had a “wake-up stroke” or the onset of symptoms was witnessed, regardless of the point in time within the late window. In fact, the benefit of intervention was greater for patients who presented in the latter part of the late time window.

Never too late for urgent medical care

“While the findings of this analysis do not contradict the mantra that the earlier treatment is instituted, the higher the chance of a good outcome, they highlight the fact that it is never too late to seek urgent medical care,” said lead investigator Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey.

“The implications of the findings from AURORA are that they could lead to a change in guidelines from endorsement of thrombectomy as level 1a recommendation in eligible patients presenting in the 6- to 16-hour time window to a 6- to 24-hour time window,” said Dr. Jovin.

“Furthermore, there are strong signals of benefit of thrombectomy in patients who are not selected based on volumetric analysis of baseline infarct (core) or extent of tissue at risk (penumbra), such that when those imaging modalities are not available or contraindicated, selection based on noncontrast CT and clinical information only may be acceptable,” he added. “Finally, the possibility of benefit from thrombectomy performed beyond 24 hours from last seen well is real and should be explored in future studies.”

The AURORA findings were presented at the virtual International Stroke Conference (ISC) 2021.

The objective of the study was to provide a more precise estimate of the benefit of thrombectomy for patients with stroke when performed within 6-24 hours after the patient was last seen well, Dr. Jovin explained.

He said the 6-hour cutoff was chosen somewhat arbitrarily, but added, “It is highly consequential, as it marks the point of demarcation between the early and late time window, and virtually all guidelines recommend different approaches, dependent on whether patients present before or after 6 hours from symptom onset.”

The 6+ hour window

Dr. Jovin pointed out that for patients who present beyond 6 hours, treatment options are more restricted, because the data on thrombectomy in this later period come mainly from two North American trials (DEFUSE 3 and DAWN) that had very stringent imaging criteria for enrollment.

“We wanted to create a heterogeneous dataset with regard to geography and selection criteria by forming the AURORA collaboration,” he commented. Their study involved an individual-level pooled analysis of all patients who underwent randomization after 6 hours from the time that they were last seen well. Patients were randomly assigned to receive either best medical therapy alone or best medical therapy plus thrombectomy (either with stent retrievers or aspiration) for anterior circulation proximal large-vessel occlusion stroke.

The data came from six trials: DAWN (which enrolled patients 6-24 hours from stroke onset), DEFUSE 3 (6-16 hours), ESCAPE (0-12 hours), REVASCAT (0-8 hours), RESILIENT (0-8 hours), and POSITIVE (0-12 hours). In total, 505 patients were included in the meta-analysis, 266 in the intervention group, and 239 in the control group.

“By pooling data on patients presenting after 6 hours from all these trails, we achieve greater precision for treatment effect estimation and increased the power for subgroup analysis,” Dr. Jovin noted.

Although the majority of the patients were in the DAWN and DIFFUSE 3 trials (n = 388), “there are still a good number from the other four trials (n = 117),” Dr. Jovin reported.

Most of the trials used Modified Rankin Scale (mRS) ordinal or shift analysis as their primary endpoint, which was the also the endpoint chosen for this meta-analysis.

Imaging selection criteria ranged from fully automated software-generated quantitative volumetric analysis of baseline infarct (core) or tissue at risk to CT perfusion and plain CT/CTA. The minimum ASPECTS score was 5 or 6.

There were no imbalances in baseline characteristics. The median NIH Stroke Scale score was 16, and the median ASPECTS score was 8. The median time to randomization was 10.5 hours.

With regard to safety, there was no significant difference in rates of symptomatic intracerebral hemorrhage (5.3% in the intervention group vs. 3.3% in the control group; P = .23) or in mortality at 90 days (16.5% vs. 19.3%; P = .87). Jovin noted that these results are very similar to those from the HERMES meta-analysis of patients treated in the early time window.

The primary outcome – ordinal analysis of the mRS distribution – showed an adjusted odds ratio of 2.54 (P < .0001) for benefit in the intervention group. The number needed to treat to reduce disability was 3. “This is again very similar to the HERMES meta-analysis of patients in the early window,” Dr. Jovin said.

The P value for heterogeneity of treatment effect across the six studies was nonsignificant.

Secondary outcome analysis showed an “almost 27%” difference in good functional outcome (MRS, 0-2) between the two groups (45.9% in the intervention group vs. 19.3% in the control group), which translates into a number needed to treat of 3.8, Dr. Jovin reported.

Subgroup analysis showed a treatment effect favoring intervention across all prespecified subgroup factors, including age, sex, occlusion location, mode of presentation (wake-up vs. witnessed), and ASPECTS score, with the caveat that most of the patients were enrolled with ASPECTS scores of 7 or greater.

Early versus late

Surprisingly, although thrombectomy was found to be beneficial in both the 6- to 12-hour and 12- to 24-hour time window, the magnitude of benefit was significantly higher in the later rather than the earlier time window. The odds ratio of a better outcome with thrombectomy on the mRS shift analysis in those presenting in the 6- to 12-hour period was 1.78, compared with 5.86 in the 12- to 24-hour time window.

“This should not be interpreted as a higher chance of a good outcome if treated late. In fact, the rate of good outcomes were numerically higher in the earlier treated patients, but the difference comes from the control group, which did much worse in patients randomized in the later time period,” Dr. Jovin said.

“Aurora was the goddess of dawn [in ancient Roman mythology], so this is a very fitting name, as it reminds us that we are in the dawn of a new era where patients are selected based on physiological data rather than on time, and we certainly hope that this work has brought us closer to this reality,” Dr. Jovin concluded.

Commenting on the study, Michael Hill, MD, University of Calgary (Alta.), said: “The work provides pooled empiric data to support the concept that time to treatment is no longer the sole threshold variable to be used in treatment decision-making. Instead, time is now simply another variable to consider in the context of clinical and imaging factors.”

Dr. Hill, who headed up the ESCAPE trial and was also involved in the current meta-analysis, added: “This meta-analysis supports the concept of patient selection using the ‘good scan’ model, rather than using a time-based concept of patient eligibility for endovascular therapy. It will further push changes in care, because the implication is that all patients with more severe acute stroke presentations need emergency neurovascular imaging to decide if they are eligible for treatment.”

The AURORA meta-analysis was funded by Stryker Neurovascular. Dr. Jovin reports stock holdings in Anaconda, Route 92, VizAi, FreeOx, Blockade Medical, Methinks, and Corindus; personal fees from Cerenovus and Contego Medical; travel support from Fundacio Ictus; and grant support from Medtronic and Stryker Neurovascular.

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

A radially adjustable stent retriever provided a high rate of substantial reperfusion and was associated with low rates of symptomatic intracranial hemorrhage and death in a new study. The novel device may increase the options for endovascular therapy, researchers say.

In this study, the Tigertriever (Rapid Medical) was noninferior to a prespecified performance goal and superior to established devices, as determined from historical rates derived from trials. The device achieved first-pass successful reperfusion in approximately 6 of 10 patients and final successful reperfusion in more than 9 of 10 patients.

“The Tigertriever is a highly effective and safe device to remove thrombus in patients with large-vessel occlusion who are eligible for mechanical thrombectomy,” Rishi Gupta, MD, a vascular neurologist at Wellstar Health System Kennestone Hospital, Marietta, Ga., said during his presentation.

Results of the TIGER trial were presented at the International Stroke Conference, sponsored by the American Heart Association, and were published online March 19, 2021, in Stroke.

Endovascular therapy significantly improves outcomes of acute ischemic stroke resulting from large-vessel occlusion. However, current devices fail to achieve successful reperfusion in approximately 27% of patients, the researchers noted. In addition, the devices are associated with complications such as embolization to a new territory and symptomatic intracranial hemorrhage.

The Tigertriever is a radially adjustable, fully visible stent retriever. The operator controls the device’s radial expansion and force, enabling the operator to minimize vessel tension. The Tigertriever is available in Europe.

Effective revascularization

Dr. Gupta and colleagues conducted the prospective, single-arm TIGER study to evaluate the safety and efficacy of the Tigertriever in restoring blood flow by removing clots for patients with ischemic stroke resulting from large-vessel occlusion. The investigators compared the performance of the Tigertriever with a composite performance goal criterion derived from six pivotal trials of the Solitaire and Trevo devices.

The researchers enrolled patients at 16 U.S. sites and one site in Israel. Eligible participants had acute ischemic stroke resulting from large-vessel occlusion and moderate to severe neurologic deficits within 8 hours of symptom onset.

The study’s primary efficacy endpoint was successful revascularization within three Tigertriever passes. The investigators defined successful revascularization as achieving a modified Thrombolysis in Cerebral Ischemia score of 2b-3. Secondary efficacy endpoints were first-pass successful revascularization and good clinical outcome, which was defined as a Modified Rankin Scale score of 0-2.

The primary safety endpoint was the composite of symptomatic intracranial hemorrhage at 24 hours and all-cause mortality at 3 months.

The researchers enrolled 160 patients between May 2018 and March 2020. The mean age of the patients was 65 years, and 61.5% were men. The median National Institutes of Health Stroke Scale score was 17. Approximately 66% of patients received tissue plasminogen activator, and the median time to tPA administration was 95 minutes.

Most occlusions were in the M1 segment of the middle cerebral artery (57.3%) or the M2 segment of the MCA (19.7%). Approximately 21% of occlusions were in the internal carotid artery.

Successful revascularization was achieved in 84.6% of participants within three passes of the Tigertriever device. This rate surpassed the 63.4% performance goal and the 73.4% historical rate.

Successful revascularization was achieved in 57.8% of cases on first pass. After three passes, the rate was 84.6%. The rate of good clinical outcome at 90 days was 58% with the Tigertriever and 43% with the historical control.

The rate of symptomatic intracranial hemorrhage at 24 hours and mortality at 90 days was 18.1% with the Tigertriever and 20.4% with the historical control.

The rates of symptomatic hemorrhage and of embolization to a new territory with the Tigertriever were lower than with other devices, despite the relatively infrequent use of balloon guide catheters in the study, said Dr. Gupta.

Unmeasured confounding

“I congratulate the TIGER investigators for an interesting study that looked at a novel stentriever with adjustable radial size and force,” said Adam de Havenon, MD, assistant professor of neurology at the University of Utah, Salt Lake City, who was asked to comment on the study. “This intuitive concept shows promise in comparison to historical controls, and I look forward to hearing more about this exciting technology.”

The major advantage of the use of a composite historical control in the study is that fewer patients are needed for a trial, said Dr. de Havenon. This design makes the trial more economical and enables it to be completed more quickly.

“The impact is that a real-world patient could receive a beneficial treatment even sooner if it was shown to be beneficial with this study design,” he added. “The disadvantage is that there is unmeasured confounding because the historical controls come from trials during different time periods and at different centers and countries, with unique demographics that may not match well with your cohort.”

Statistical methodology helps mitigate this unmeasured confounding, but it remains a concern in the quest for a high level of evidence, Dr. de Havenon added.

The data suggest that the Tigertriever is a viable alternative to other stent retrievers, but they do not support its preferential use. “If the goal is to have the Tigertriever be considered a viable treatment option for large-vessel occlusion stroke, then [the researchers] have accomplished that with this study, which provides the needed data for FDA approval of the device,” said Dr. de Havenon.

“However, these data introduce the possibility of superiority but do not definitely show that,” he concluded. “To do so, they would need a randomized trial with a comparator device or devices and, as a result, a larger sample size.”

The study was funded by Rapid Medical. Dr. Gupta was one of the principal investigators for this study and for studies sponsored by Stryker Neurovascular, Zoll, and Vesalio. He served on the clinical events committee of a trial sponsored by Penumbra and has acted as a consultant for Cerenovous. Dr de Havenon disclosed no relevant financial relationships.

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

A radially adjustable stent retriever provided a high rate of substantial reperfusion and was associated with low rates of symptomatic intracranial hemorrhage and death in a new study. The novel device may increase the options for endovascular therapy, researchers say.

In this study, the Tigertriever (Rapid Medical) was noninferior to a prespecified performance goal and superior to established devices, as determined from historical rates derived from trials. The device achieved first-pass successful reperfusion in approximately 6 of 10 patients and final successful reperfusion in more than 9 of 10 patients.

“The Tigertriever is a highly effective and safe device to remove thrombus in patients with large-vessel occlusion who are eligible for mechanical thrombectomy,” Rishi Gupta, MD, a vascular neurologist at Wellstar Health System Kennestone Hospital, Marietta, Ga., said during his presentation.

Results of the TIGER trial were presented at the International Stroke Conference, sponsored by the American Heart Association, and were published online March 19, 2021, in Stroke.

Endovascular therapy significantly improves outcomes of acute ischemic stroke resulting from large-vessel occlusion. However, current devices fail to achieve successful reperfusion in approximately 27% of patients, the researchers noted. In addition, the devices are associated with complications such as embolization to a new territory and symptomatic intracranial hemorrhage.

The Tigertriever is a radially adjustable, fully visible stent retriever. The operator controls the device’s radial expansion and force, enabling the operator to minimize vessel tension. The Tigertriever is available in Europe.

Effective revascularization

Dr. Gupta and colleagues conducted the prospective, single-arm TIGER study to evaluate the safety and efficacy of the Tigertriever in restoring blood flow by removing clots for patients with ischemic stroke resulting from large-vessel occlusion. The investigators compared the performance of the Tigertriever with a composite performance goal criterion derived from six pivotal trials of the Solitaire and Trevo devices.

The researchers enrolled patients at 16 U.S. sites and one site in Israel. Eligible participants had acute ischemic stroke resulting from large-vessel occlusion and moderate to severe neurologic deficits within 8 hours of symptom onset.

The study’s primary efficacy endpoint was successful revascularization within three Tigertriever passes. The investigators defined successful revascularization as achieving a modified Thrombolysis in Cerebral Ischemia score of 2b-3. Secondary efficacy endpoints were first-pass successful revascularization and good clinical outcome, which was defined as a Modified Rankin Scale score of 0-2.

The primary safety endpoint was the composite of symptomatic intracranial hemorrhage at 24 hours and all-cause mortality at 3 months.

The researchers enrolled 160 patients between May 2018 and March 2020. The mean age of the patients was 65 years, and 61.5% were men. The median National Institutes of Health Stroke Scale score was 17. Approximately 66% of patients received tissue plasminogen activator, and the median time to tPA administration was 95 minutes.

Most occlusions were in the M1 segment of the middle cerebral artery (57.3%) or the M2 segment of the MCA (19.7%). Approximately 21% of occlusions were in the internal carotid artery.

Successful revascularization was achieved in 84.6% of participants within three passes of the Tigertriever device. This rate surpassed the 63.4% performance goal and the 73.4% historical rate.

Successful revascularization was achieved in 57.8% of cases on first pass. After three passes, the rate was 84.6%. The rate of good clinical outcome at 90 days was 58% with the Tigertriever and 43% with the historical control.

The rate of symptomatic intracranial hemorrhage at 24 hours and mortality at 90 days was 18.1% with the Tigertriever and 20.4% with the historical control.

The rates of symptomatic hemorrhage and of embolization to a new territory with the Tigertriever were lower than with other devices, despite the relatively infrequent use of balloon guide catheters in the study, said Dr. Gupta.

Unmeasured confounding

“I congratulate the TIGER investigators for an interesting study that looked at a novel stentriever with adjustable radial size and force,” said Adam de Havenon, MD, assistant professor of neurology at the University of Utah, Salt Lake City, who was asked to comment on the study. “This intuitive concept shows promise in comparison to historical controls, and I look forward to hearing more about this exciting technology.”

The major advantage of the use of a composite historical control in the study is that fewer patients are needed for a trial, said Dr. de Havenon. This design makes the trial more economical and enables it to be completed more quickly.

“The impact is that a real-world patient could receive a beneficial treatment even sooner if it was shown to be beneficial with this study design,” he added. “The disadvantage is that there is unmeasured confounding because the historical controls come from trials during different time periods and at different centers and countries, with unique demographics that may not match well with your cohort.”

Statistical methodology helps mitigate this unmeasured confounding, but it remains a concern in the quest for a high level of evidence, Dr. de Havenon added.

The data suggest that the Tigertriever is a viable alternative to other stent retrievers, but they do not support its preferential use. “If the goal is to have the Tigertriever be considered a viable treatment option for large-vessel occlusion stroke, then [the researchers] have accomplished that with this study, which provides the needed data for FDA approval of the device,” said Dr. de Havenon.

“However, these data introduce the possibility of superiority but do not definitely show that,” he concluded. “To do so, they would need a randomized trial with a comparator device or devices and, as a result, a larger sample size.”

The study was funded by Rapid Medical. Dr. Gupta was one of the principal investigators for this study and for studies sponsored by Stryker Neurovascular, Zoll, and Vesalio. He served on the clinical events committee of a trial sponsored by Penumbra and has acted as a consultant for Cerenovous. Dr de Havenon disclosed no relevant financial relationships.

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

A radially adjustable stent retriever provided a high rate of substantial reperfusion and was associated with low rates of symptomatic intracranial hemorrhage and death in a new study. The novel device may increase the options for endovascular therapy, researchers say.

In this study, the Tigertriever (Rapid Medical) was noninferior to a prespecified performance goal and superior to established devices, as determined from historical rates derived from trials. The device achieved first-pass successful reperfusion in approximately 6 of 10 patients and final successful reperfusion in more than 9 of 10 patients.

“The Tigertriever is a highly effective and safe device to remove thrombus in patients with large-vessel occlusion who are eligible for mechanical thrombectomy,” Rishi Gupta, MD, a vascular neurologist at Wellstar Health System Kennestone Hospital, Marietta, Ga., said during his presentation.

Results of the TIGER trial were presented at the International Stroke Conference, sponsored by the American Heart Association, and were published online March 19, 2021, in Stroke.

Endovascular therapy significantly improves outcomes of acute ischemic stroke resulting from large-vessel occlusion. However, current devices fail to achieve successful reperfusion in approximately 27% of patients, the researchers noted. In addition, the devices are associated with complications such as embolization to a new territory and symptomatic intracranial hemorrhage.

The Tigertriever is a radially adjustable, fully visible stent retriever. The operator controls the device’s radial expansion and force, enabling the operator to minimize vessel tension. The Tigertriever is available in Europe.

Effective revascularization

Dr. Gupta and colleagues conducted the prospective, single-arm TIGER study to evaluate the safety and efficacy of the Tigertriever in restoring blood flow by removing clots for patients with ischemic stroke resulting from large-vessel occlusion. The investigators compared the performance of the Tigertriever with a composite performance goal criterion derived from six pivotal trials of the Solitaire and Trevo devices.

The researchers enrolled patients at 16 U.S. sites and one site in Israel. Eligible participants had acute ischemic stroke resulting from large-vessel occlusion and moderate to severe neurologic deficits within 8 hours of symptom onset.

The study’s primary efficacy endpoint was successful revascularization within three Tigertriever passes. The investigators defined successful revascularization as achieving a modified Thrombolysis in Cerebral Ischemia score of 2b-3. Secondary efficacy endpoints were first-pass successful revascularization and good clinical outcome, which was defined as a Modified Rankin Scale score of 0-2.

The primary safety endpoint was the composite of symptomatic intracranial hemorrhage at 24 hours and all-cause mortality at 3 months.

The researchers enrolled 160 patients between May 2018 and March 2020. The mean age of the patients was 65 years, and 61.5% were men. The median National Institutes of Health Stroke Scale score was 17. Approximately 66% of patients received tissue plasminogen activator, and the median time to tPA administration was 95 minutes.

Most occlusions were in the M1 segment of the middle cerebral artery (57.3%) or the M2 segment of the MCA (19.7%). Approximately 21% of occlusions were in the internal carotid artery.

Successful revascularization was achieved in 84.6% of participants within three passes of the Tigertriever device. This rate surpassed the 63.4% performance goal and the 73.4% historical rate.

Successful revascularization was achieved in 57.8% of cases on first pass. After three passes, the rate was 84.6%. The rate of good clinical outcome at 90 days was 58% with the Tigertriever and 43% with the historical control.

The rate of symptomatic intracranial hemorrhage at 24 hours and mortality at 90 days was 18.1% with the Tigertriever and 20.4% with the historical control.

The rates of symptomatic hemorrhage and of embolization to a new territory with the Tigertriever were lower than with other devices, despite the relatively infrequent use of balloon guide catheters in the study, said Dr. Gupta.

Unmeasured confounding

“I congratulate the TIGER investigators for an interesting study that looked at a novel stentriever with adjustable radial size and force,” said Adam de Havenon, MD, assistant professor of neurology at the University of Utah, Salt Lake City, who was asked to comment on the study. “This intuitive concept shows promise in comparison to historical controls, and I look forward to hearing more about this exciting technology.”

The major advantage of the use of a composite historical control in the study is that fewer patients are needed for a trial, said Dr. de Havenon. This design makes the trial more economical and enables it to be completed more quickly.

“The impact is that a real-world patient could receive a beneficial treatment even sooner if it was shown to be beneficial with this study design,” he added. “The disadvantage is that there is unmeasured confounding because the historical controls come from trials during different time periods and at different centers and countries, with unique demographics that may not match well with your cohort.”

Statistical methodology helps mitigate this unmeasured confounding, but it remains a concern in the quest for a high level of evidence, Dr. de Havenon added.

The data suggest that the Tigertriever is a viable alternative to other stent retrievers, but they do not support its preferential use. “If the goal is to have the Tigertriever be considered a viable treatment option for large-vessel occlusion stroke, then [the researchers] have accomplished that with this study, which provides the needed data for FDA approval of the device,” said Dr. de Havenon.

“However, these data introduce the possibility of superiority but do not definitely show that,” he concluded. “To do so, they would need a randomized trial with a comparator device or devices and, as a result, a larger sample size.”

The study was funded by Rapid Medical. Dr. Gupta was one of the principal investigators for this study and for studies sponsored by Stryker Neurovascular, Zoll, and Vesalio. He served on the clinical events committee of a trial sponsored by Penumbra and has acted as a consultant for Cerenovous. Dr de Havenon disclosed no relevant financial relationships.

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

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.

Recommendations for prescribing exercise to control high blood pressure have been put forward by various medical organizations and expert panels, but finding the bandwidth to craft personalized exercise training for their patients poses a challenge for clinicians.

Now, European cardiology societies have issued a consensus statement that offers an algorithm of sorts for developing personalized exercise programs as part of overall management approach for patients with or at risk of high BP.

The statement, published in the European Journal of Preventive Cardiology and issued by the European Association of Preventive Cardiology and the European Society of Cardiology Council on Hypertension, claims to be the first document to focus on personalized exercise for BP.

The statement draws on a systematic review, including meta-analyses, to produce guidance on how to lower BP in three specific types of patients: Those with hypertension (>140/90 mm Hg), high-normal blood pressure (130-139/85-89 mm Hg), and normal blood pressure (<130/84 mm Hg).

By making recommendations for these three specific groups, along with providing guidance for combined exercise – that is, blending aerobic exercise with resistance training (RT) – the consensus statement goes one step further than recommendations other organizations have issued, Matthew W. Martinez, MD, said in an interview.

“What it adds is an algorithmic approach, if you will,” said Dr. Martinez, a sports medicine cardiologist at Morristown (N.J.) Medical Center. “There are some recommendations to help the clinicians to decide what they’re going to offer individuals, but what’s a challenge for us when seeing patients is finding the time to deliver the message and explain how valuable nutrition and exercise are.”

Guidelines, updates, and statements that include the role of exercise in BP control have been issued by the European Society of Cardiology, American Heart Association, and American College of Sports Medicine (Med Sci Sports Exercise. 2019;51:1314-23).

The European consensus statement includes the expected range of BP lowering for each activity. For example, aerobic exercise for patients with hypertension should lead to a reduction from –4.9 to –12 mm Hg systolic and –3.4 to –5.8 mm Hg diastolic.

The consensus statement recommends the following exercise priorities based on a patient’s blood pressure:

• Hypertension: Aerobic training (AT) as a first-line exercise therapy; and low- to moderate-intensity RT – equally using dynamic and isometric RT – as second-line therapy. In non-White patients, dynamic RT should be considered as a first-line therapy. RT can be combined with aerobic exercise on an individual basis if the clinician determines either form of RT would provide a metabolic benefit.
• High-to-normal BP: Dynamic RT as a first-line exercise, which the systematic review determined led to greater BP reduction than that of aerobic training. “Isometric RT is likely to elicit similar if not superior BP-lowering effects as [dynamic RT], but the level of evidence is low and the available data are scarce,” wrote first author Henner Hanssen, MD, of the University of Basel, Switzerland, and coauthors. Combining dynamic resistance training with aerobic training “may be preferable” to dynamic RT alone in patients with a combination of cardiovascular risk factors.
• Normal BP: Isometric RT may be indicated as a first-line intervention in individuals with a family or gestational history or obese or overweight people currently with normal BP. This advice includes a caveat: “The number of studies is limited and the 95% confidence intervals are large,” Dr. Hanssen and coauthors noted. AT is also an option in these patients, with more high-quality meta-analyses than the recommendation for isometric RT. “Hence, the BP-lowering effects of [isometric RT] as compared to AT may be overestimated and both exercise modalities may have similar BP-lowering effects in individuals with normotension,” wrote the consensus statement authors.

They note that more research is needed to validate the BP-lowering effects of combined exercise.

The statement acknowledges the difficulty clinicians face in managing patients with high blood pressure. “From a socioeconomic health perspective, it is a major challenge to develop, promote, and implement individually tailored exercise programs for patients with hypertension under consideration of sustainable costs,” wrote Dr. Hanssen and coauthors.

Dr. Martinez noted that one strength of the consensus statement is that it addresses the impact exercise can have on vascular health and metabolic function. And, it points out existing knowledge gaps.

“Are we going to see greater applicability of this as we use IT health technology?” he asked. “Are wearables and telehealth going to help deliver this message more easily, more frequently? Is there work to be done in terms of differences in gender? Do men and women respond differently, and is there a different exercise prescription based on that as well as ethnicity? We well know there’s a different treatment for African Americans compared to other ethnic groups.”

The statement also raises the stakes for using exercise as part of a multifaceted, integrated approach to hypertension management, he said.

“It’s not enough to talk just about exercise or nutrition, or to just give an antihypertension medicine,” Dr. Martinez said. “Perhaps the sweet spot is in integrating an approach that includes all three.”

Consensus statement coauthor Antonio Coca, MD, reported financial relationships with Abbott, Berlin-Chemie, Biolab, Boehringer-Ingelheim, Ferrer, Menarini, Merck, Novartis and Sanofi-Aventis. Coauthor Maria Simonenko, MD, reported financial relationships with Novartis and Sanofi-Aventis. Linda Pescatello, PhD, is lead author of the American College of Sports Medicine 2019 statement. Dr. Hanssen and all other authors have no disclosures. Dr. Martinez has no relevant relationships to disclose.

Patients with suspected large-vessel occlusion stroke who were taken directly to the angiography suite, bypassing the emergency department, received endovascular treatment faster and had better 90-day functional outcomes in a new study.

Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.

The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.

In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.

If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
 

Bypassing the emergency department

Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.

If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.

Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.

After CT scanning, patients received thrombolysis as recommended in the guidelines.

The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.

Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).

The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).

There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)

Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.

“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”

Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”

A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.

He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
 

The cost of speed

Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.

He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.

“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”

The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.

Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”

Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”

The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.

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

Patients with suspected large-vessel occlusion stroke who were taken directly to the angiography suite, bypassing the emergency department, received endovascular treatment faster and had better 90-day functional outcomes in a new study.

Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.

The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.

In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.

If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
 

Bypassing the emergency department

Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.

If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.

Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.

After CT scanning, patients received thrombolysis as recommended in the guidelines.

The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.

Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).

The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).

There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)

Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.

“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”

Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”

A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.

He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
 

The cost of speed

Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.

He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.

“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”

The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.

Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”

Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”

The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.

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

Patients with suspected large-vessel occlusion stroke who were taken directly to the angiography suite, bypassing the emergency department, received endovascular treatment faster and had better 90-day functional outcomes in a new study.

Results of the ANGIO-CAT trial were presented at the International Stroke Conference sponsored by the American Heart Association.

The study involved patients suspected of having a large-vessel occlusion, as assessed in the prehospital setting by paramedics using the Rapid Arterial Occlusion Evaluation (RACE) score.

In his presentation, Manuel Requena, PhD, a neurologist and neurointerventionalist fellow at Vall d’Hebron Hospital, Barcelona, explained that, if patients were within 6 hours of symptom onset with a RACE scale score greater than 4, paramedics called ahead to a stroke neurologist, who met the patient directly at the hospital.

If on clinical examination the National Institutes of Health Stroke Scale (NIHSS) score was greater than 10, patients could be enrolled into the study. Upon enrollment, they were randomly assigned either to be taken directly to the angiography suite or to receive standard care.
 

Bypassing the emergency department

Dr. Requena noted that, at his center, patients who receive standard care are transferred to the CT imaging suite, where they are evaluated with noncontrast CT and CT angiography. CT perfusion is also performed if the treating physician deems it necessary.

If a large-vessel occlusion is confirmed, patients are then transferred to the angiography suite for endovascular treatment. He added that in many centers, patients are evaluated in the ED before undergoing CT scanning.

Patients in the direct angiography group received a “flat-panel” noncontrast CT in the angiography suite to rule out intracranial hemorrhage or a large, established infarct. The large-vessel occlusion would be confirmed by arteriography before the endovascular procedure was performed.

After CT scanning, patients received thrombolysis as recommended in the guidelines.

The current interim analysis includes the 174 patients who have been enrolled so far in the study. The median RACE score for these patients was 7, and the median NIHSS score was 17. Large-vessel occlusion was confirmed in 84% of patients, and 8% had an intracerebral hemorrhage.

Results showed that of the 147 patients who received endovascular therapy, puncture time was shorter for those who were taken directly to angiography (median, 18 min vs. 42 min), as was time to reperfusion (median, 57 min vs. 84 min).

The primary outcome was a shift analysis of the Modified Rankin Scale functional outcome scale at 90 days (odds of 1-point improvement or more). In the direct angiography group, the adjusted odds ratio for an improved functional outcome was 2.2 (95% confidence interval, 1.2-.1).

There were no significant differences in safety endpoints. There was a trend toward more procedural complications in those receiving endovascular therapy in the direct angiography group (8.1% vs. 2.7%; P = .6), but there was also a trend toward lower 90-day mortality in this group (20.2% vs. 32.9%; P = .07)

Dr. Requena reported no significant difference in safety outcomes among those with a hemorrhagic stroke.

“Our study is the first clinical trial that shows the superiority of direct transfer to an angiography suite,” said Dr. Requena. “Our findings were close to what we expected, and we were surprised that they occurred so early in the study. We trust that they will be confirmed in ongoing, multicenter, international trials.”

Stroke patients who were transferred directly to an angiography suite were also less likely to be dependent on assistance with daily activities than were those who received the current standard of care, Dr. Requena said. “More frequent and more rapid treatment can help improve outcomes for our stroke patients.”

A limitation of this study is that the hospital had extensive experience with immediate angiography, so findings may differ at hospitals or care centers with less angiography expertise or experience, Dr. Requena said.

He added that retrospective studies conducted in hospitals in the United States, Germany, and Switzerland show that this kind of protocol can be developed in any high-volume stroke center, although multicenter, international trials are needed.
 

The cost of speed

Commenting on the ANGIO-CAT study, Michael Hill, MD, a professor at the University of Calgary (Alta.), said the 27-minute improvement in door-to-reperfusion time achieved in the study was meaningful and correlates with the degree of improved outcomes observed. “So, the improvement in speed of treatment resulting in better outcomes makes sense,” he added.

He cautioned that this strategy would only be feasible in certain centers with selected patients and that cost will be a fundamental issue.

“If you identify patients at angiography, you risk having some patients with no target large-vessel occlusion,” Dr. Hill added. “The real question is, how many of these patients without a large-vessel occlusion can the system tolerate before it becomes uneconomical and not fruitful or harmful, given that groin puncture is not totally harmless?”

The moderator of the ISC news conference on the study, Mitchell Elkind, MD, professor of neurology at Columbia University, New York, who is also president of the American Stroke Association, said the study reflects the growing recognition of the importance of speed when treating stroke. “If we can shorten time to treatment using rapid evaluation and imaging protocols, this will help save brain,” he said.

Also commenting on the study, Louisa McCullough, MD, PhD, chief of neurology at Memorial Hermann Hospital–Texas Medical Center, Houston, who is the ISC meeting chair, said she thought the study would be relevant to the United States. “Speed is really of the essence. Whenever we can reduce delays, that will make a big difference to patients.”

Referring to this study on improving hospital systems, as well as a second study that was presented at the meeting that showed benefits from delivery of prehospital thrombolysis via a mobile stroke unit, Dr. McCullough added that “we need to set up models so we can get the best of both these worlds. These studies are really leading the way on how we can change the stroke systems of care.”

The study was funded by Vall d’Hebron Research Institute. Dr. Requena disclosed no relevant financial relationships.

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

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

Eating ultraprocessed foods poses a significant risk to cardiovascular and coronary heart health, according to prospective data from about 3,000 people in the Framingham Offspring Cohort, the second generation of participants in the Framingham Heart Study.

©Ingram Publishing/Thinkstock.com

Each regular, daily serving of ultraprocessed food was linked with significant elevations of 5%-9% in the relative rates of “hard” cardiovascular disease (CVD) events, hard coronary heart disease (CHD) events, overall CVD events, and CVD death, after adjustments for numerous potential confounders including energy intake, body mass index, waist circumference, and blood pressure, Filippa Juul, PhD, and associates wrote in a report published in the Journal of the American College of Cardiology.

“Consumption of ultraprocessed foods makes up over half of the daily calories in the average American diet and are increasingly consumed worldwide. As poor diet is a major modifiable risk factor for heart disease, it represents a critical target in prevention efforts,” said Dr. Juul, a nutritional epidemiologist at New York University, in a statement released by the American College of Cardiology.

“Our findings add to a growing body of evidence suggesting cardiovascular benefits of limiting ultraprocessed foods. Ultraprocessed foods are ubiquitous and include many foods that are marketed as healthy, such as protein bars, breakfast cereals, and most industrially produced breads,” she added. Other commonplace members of the ultraprocessed food group include carbonated soft drinks, packaged snacks, candies, sausages, margarines, and energy drinks. The concept of ultraprocessed foods as a distinct, wide-ranging, and dangerous food category first appeared in 2010, and then received an update from a United Nations panel in 2019 as what’s now called the NOVA classification system.
 

Ultraprocessed foods fly under the radar

“Although cardiovascular guidelines emphasize consuming minimally processed foods, such as fruits, vegetables, whole grains, and nuts, they give less attention to the importance of minimizing ultraprocessed food,” wrote Robert J. Ostfeld, MD, and Kathleen E. Allen, MS, in an editorial that accompanied the new report. This reduced attention may be because of a “paucity of studies examining the association cardiovascular outcomes and ultraprocessed foods.”

The new evidence demands new policies, educational efforts, and labeling changes, suggested Dr. Ostfeld, director of preventive cardiology at Montefiore Health System in New York, and Ms. Allen, a dietitian at the Geisel School of Medicine at Dartmouth, Hanover, N.H. “The goal should be to make the unhealthy choice the hard choice and the healthy choice the easy choice.”

The new analysis used data collected from people enrolled the Framingham Offspring Cohort, with their clinical metrics and diet information collected during 1991-1995 serving as their baseline. After excluding participants with prevalent CVD at baseline and those with incomplete follow-up of CVD events, the researchers had a cohort of 3,003 adults with an average follow-up of 18 years. At baseline, the cohort averaged 54 years of age; 55% were women, their average body mass index was 27.3 kg/m², and about 6% had diabetes. They reported eating, on average, 7.5 servings of ultraprocessed food daily.

During follow-up, the cohort tallied 648 incident CVD events, including 251 hard CVD events (coronary death, MI, or stroke) and 163 hard CHD events (coronary death or MI), and 713 total deaths including 108 CVD deaths. Other CVD events recorded but not considered hard included heart failure, intermittent claudication, and transient ischemic attack.

In a multivariate-adjusted analysis, each average daily portion of ultraprocessed food was linked with an significant 7% relative increase in the incidence of a hard CVD event, compared with participants who ate fewer ultraprocessed food portions, and a 9% relative increase in the rate of hard CHD events, the study’s two prespecified primary outcomes. The researchers also found that each ultraprocessed serving significantly was associated with a 5% relative increased rate of total CVD events, and a 9% relative rise in CVD deaths. The analysis showed no significant association between total mortality and ultraprocessed food intake. (Average follow-up for the mortality analyses was 20 years.)

The authors also reported endpoint associations with intake of specific types of ultraprocessed foods, and found significantly increased associations specifically for portions of bread, ultraprocessed meat, salty snacks, and low-calorie soft drinks.

Convenient, omnipresent, and affordable

The authors acknowledged that the associations they found need examination in ethnically diverse populations, but nonetheless the findings “suggest the need for increased efforts to implement population-wide strategies” to lower consumption of ultraprocessed foods. “Given the convenience, omnipresence, and affordability of ultraprocessed foods, careful nutrition counseling is needed to design individualized, patient-centered, heart-healthy diets,” they concluded.

“Population-wide strategies such as taxation on sugar-sweetened beverages and other ultraprocessed foods and recommendations regarding processing levels in national dietary guidelines are needed to reduce the intake of ultraprocessed foods,” added Dr. Juul in her statement. “Of course, we must also implement policies that increase the availability, accessibility, and affordability of nutritious, minimally processed foods, especially in disadvantaged populations. At the clinical level, there is a need for increased commitment to individualized nutrition counseling for adopting sustainable heart-healthy diets.”

The study had no commercial funding. Dr. Juul and coauthors, Dr. Ostfeld, and Ms. Allen had no disclosures.

[email protected]

More than one-third of adults aged 18-64 years in the United States delayed or went without medical care because of efforts by patients or providers to reduce the spread of COVID-19, according to a new report from the Urban Institute.

Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.

The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.

Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.

Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.

“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.

Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.

In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.

Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.

“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
 

Lost lives

Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.

“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.

During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.

“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”

Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.

In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
 

Care most often skipped

The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.

Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).

Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).

The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.

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

More than one-third of adults aged 18-64 years in the United States delayed or went without medical care because of efforts by patients or providers to reduce the spread of COVID-19, according to a new report from the Urban Institute.

Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.

The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.

Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.

Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.

“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.

Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.

In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.

Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.

“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
 

Lost lives

Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.

“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.

During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.

“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”

Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.

In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
 

Care most often skipped

The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.

Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).

Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).

The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.

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

More than one-third of adults aged 18-64 years in the United States delayed or went without medical care because of efforts by patients or providers to reduce the spread of COVID-19, according to a new report from the Urban Institute.

Among the adults who postponed or missed care, 32.6% said the gap worsened one or more health conditions or limited their ability to work or perform daily activities. The findings highlight “the detrimental ripple effects of delaying or forgoing care on overall health, functioning, and well-being,” researchers write.

The survey, conducted among 4,007 U.S. adults aged 18-64 in September 2020, found that adults with one or more chronic conditions were more likely than adults without chronic conditions to have delayed or missed care (40.7% vs. 26.4%). Adults with a mental health condition were particularly likely to have delayed or gone without care, write Dulce Gonzalez, MPP, a research associate in the Health Policy Center at the Urban Institute, and colleagues.

Doctors are already seeing the consequences of the missed visits, says Jacqueline W. Fincher, MD, president of the American College of Physicians.

Two of her patients with chronic conditions missed appointments last year. By the time they resumed care in 2021, their previsit lab tests showed significant kidney deterioration.

“Lo and behold, their kidneys were in failure. … One was in the hospital for 3 days and the other one was in for 5 days,” said Dr. Fincher, who practices general internal medicine in Georgia.

Dr. Fincher’s office has been proactive about calling patients with chronic diseases who missed follow-up visits or laboratory testing or who may have run out of medication, she said.

In her experience, delays mainly have been because of patients postponing visits. “We have stayed open the whole time now,” Dr. Fincher said. Her office offers telemedicine visits and in-person visits with safety precautions.

Still, some patients have decided to postpone care during the pandemic instead of asking their primary care doctor what they should do.

“We do know that chronic problems left without appropriate follow-up can create worse problems for them in terms of stroke, heart attack, and end organ damage,” Dr. Fincher said.
 

Lost lives

Future studies may help researchers understand the effects of delayed and missed care during the pandemic, said Russell S. Phillips, MD, director of the Center for Primary Care at Harvard Medical School, Boston.

“Although it is still early, and more data on patient outcomes will need to be collected, I anticipate that the ... delays in diagnosis, in cancer screening, and in management of chronic illness will result in lost lives and will emphasize the important role that primary care plays in saving lives,” Dr. Phillips said.

During the first several months of the pandemic, there were fewer diagnoses of hypertension, diabetes, and depression, Dr. Phillips said.

“In addition, and most importantly, the mortality rate for non-COVID conditions increased, suggesting that patients were not seeking care for symptoms of stroke or heart attack, which can be fatal if untreated,” he said. “We have also seen substantial decreases in cancer screening tests such as colonoscopy, and modeling studies suggest this will cost more lives based on delayed diagnoses of cancer.”

Vaccinating patients against COVID-19 may help primary care practices and patients get back on track, Dr. Phillips suggested.

In the meantime, some patients remain reluctant to come in. “Volumes are still lower than prepandemic, so it is challenging to overcome what is likely to be pent-up demand,” he told this news organization in an email. “Additionally, the continued burden of evaluating, testing, and monitoring patients with COVID or COVID-like symptoms makes it difficult to focus on chronic illness.”
 

Care most often skipped

The Urban Institute survey asked respondents about delays in prescription drugs, general doctor and specialist visits, going to a hospital, preventive health screenings or medical tests, treatment or follow-up care, dental care, mental health care or counseling, treatment or counseling for alcohol or drug use, and other types of medical care.

Dental care was the most common type of care that adults delayed or did not receive because of the pandemic (25.3%), followed by general doctor or specialist visits (20.6%) and preventive health screenings or medical tests (15.5%).

Black adults were more likely than White or Hispanic/Latinx adults to have delayed or forgone care (39.7% vs. 34.3% and 35.5%), the researchers found. Compared with adults with higher incomes, adults with lower incomes were more likely to have missed multiple types of care (26.6% vs. 20.3%).

The report by the Urban Institute researchers was supported by the Robert Wood Johnson Foundation. Dr. Phillips is an adviser to two telemedicine companies, Bicycle Health and Grow Health. Dr. Fincher has disclosed no relevant financial disclosures.

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

Contrary to previous findings, selective serotonin reuptake inhibitors are not associated with an increased risk of intracerebral hemorrhage (ICH), results of a large observational study show. However, at least one expert urged caution in interpreting the finding.

“These findings are important, especially since depression is common after stroke and SSRIs are some of the first drugs considered for people,” Mithilesh Siddu, MD, of the University of Miami/Jackson Memorial Hospital, also in Miami, said in a statement.

However, Dr. Siddu said “more research is needed to confirm our findings and to also examine if SSRIs prescribed after a stroke may be linked to risk of a second stroke.”

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Widely prescribed

SSRIs, the most widely prescribed antidepressant in the United States, have previously been linked to an increased risk of ICH, possibly as a result of impaired platelet function.

To investigate further, the researchers analyzed data from the Florida Stroke Registry (FSR). They identified 127,915 patients who suffered ICH from January 2010 to December 2019 and for whom information on antidepressant use was available.

They analyzed the proportion of cases presenting with ICH among antidepressant users and the rate of SSRI prescription among stroke patients discharged on antidepressant therapy.

The researchers found that 11% of those who had been prescribed antidepressants had an ICH, compared with 14% of those who had not.

Antidepressant users were more likely to be female; non-Hispanic White; have hypertension; have diabetes; and use oral anticoagulants, antiplatelets, and statins prior to hospital presentation for ICH.

In multivariable analyses adjusting for age, race, prior history of hypertension, diabetes and prior oral anticoagulant, antiplatelet and statin use, antidepressant users were just as likely to present with spontaneous ICH as nonantidepressant users (odds ratio, 0.92; 95% confidence interval, 0.85-1.01).

A total of 3.4% of all ICH patients and 9% of those in whom specific antidepressant information was available were discharged home on an antidepressant, most commonly an SSRI (74%).

The authors noted a key limitation of the study: Some details regarding the length, dosage, and type of antidepressants were not available.
 

Interpret with caution

In a comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of the Global Neuroscience Initiative Foundation, urged caution in making any firm conclusions based on this study.

“We have two questions here: One, is SSRI use a risk factor for first-time intracerebral hemorrhage, and two, is SSRI use after an ICH a risk factor for additional hemorrhages,” said Dr. Lakhan, who was not involved with the study.

“This study incompletely addresses the first because it is known that SSRIs have a variety of potencies. For instance, paroxetine is a strong inhibitor of serotonin reuptake, whereas bupropion is weak. Hypothetically, the former has a greater risk of ICH. Because this study did not stratify by type of antidepressant, it is not possible to tease these out,” Dr. Lakhan said.

“The second question is completely unaddressed by this study and is the real concern in clinical practice, because the chance of rebleed is much higher than the risk of first-time ICH in the general population,” he added.

The study had no specific funding. Dr. Siddu and Dr. Lakhan disclosed no relevant financial relationships.

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

Contrary to previous findings, selective serotonin reuptake inhibitors are not associated with an increased risk of intracerebral hemorrhage (ICH), results of a large observational study show. However, at least one expert urged caution in interpreting the finding.

“These findings are important, especially since depression is common after stroke and SSRIs are some of the first drugs considered for people,” Mithilesh Siddu, MD, of the University of Miami/Jackson Memorial Hospital, also in Miami, said in a statement.

However, Dr. Siddu said “more research is needed to confirm our findings and to also examine if SSRIs prescribed after a stroke may be linked to risk of a second stroke.”

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Widely prescribed

SSRIs, the most widely prescribed antidepressant in the United States, have previously been linked to an increased risk of ICH, possibly as a result of impaired platelet function.

To investigate further, the researchers analyzed data from the Florida Stroke Registry (FSR). They identified 127,915 patients who suffered ICH from January 2010 to December 2019 and for whom information on antidepressant use was available.

They analyzed the proportion of cases presenting with ICH among antidepressant users and the rate of SSRI prescription among stroke patients discharged on antidepressant therapy.

The researchers found that 11% of those who had been prescribed antidepressants had an ICH, compared with 14% of those who had not.

Antidepressant users were more likely to be female; non-Hispanic White; have hypertension; have diabetes; and use oral anticoagulants, antiplatelets, and statins prior to hospital presentation for ICH.

In multivariable analyses adjusting for age, race, prior history of hypertension, diabetes and prior oral anticoagulant, antiplatelet and statin use, antidepressant users were just as likely to present with spontaneous ICH as nonantidepressant users (odds ratio, 0.92; 95% confidence interval, 0.85-1.01).

A total of 3.4% of all ICH patients and 9% of those in whom specific antidepressant information was available were discharged home on an antidepressant, most commonly an SSRI (74%).

The authors noted a key limitation of the study: Some details regarding the length, dosage, and type of antidepressants were not available.
 

Interpret with caution

In a comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of the Global Neuroscience Initiative Foundation, urged caution in making any firm conclusions based on this study.

“We have two questions here: One, is SSRI use a risk factor for first-time intracerebral hemorrhage, and two, is SSRI use after an ICH a risk factor for additional hemorrhages,” said Dr. Lakhan, who was not involved with the study.

“This study incompletely addresses the first because it is known that SSRIs have a variety of potencies. For instance, paroxetine is a strong inhibitor of serotonin reuptake, whereas bupropion is weak. Hypothetically, the former has a greater risk of ICH. Because this study did not stratify by type of antidepressant, it is not possible to tease these out,” Dr. Lakhan said.

“The second question is completely unaddressed by this study and is the real concern in clinical practice, because the chance of rebleed is much higher than the risk of first-time ICH in the general population,” he added.

The study had no specific funding. Dr. Siddu and Dr. Lakhan disclosed no relevant financial relationships.

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

Contrary to previous findings, selective serotonin reuptake inhibitors are not associated with an increased risk of intracerebral hemorrhage (ICH), results of a large observational study show. However, at least one expert urged caution in interpreting the finding.

“These findings are important, especially since depression is common after stroke and SSRIs are some of the first drugs considered for people,” Mithilesh Siddu, MD, of the University of Miami/Jackson Memorial Hospital, also in Miami, said in a statement.

However, Dr. Siddu said “more research is needed to confirm our findings and to also examine if SSRIs prescribed after a stroke may be linked to risk of a second stroke.”

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Widely prescribed

SSRIs, the most widely prescribed antidepressant in the United States, have previously been linked to an increased risk of ICH, possibly as a result of impaired platelet function.

To investigate further, the researchers analyzed data from the Florida Stroke Registry (FSR). They identified 127,915 patients who suffered ICH from January 2010 to December 2019 and for whom information on antidepressant use was available.

They analyzed the proportion of cases presenting with ICH among antidepressant users and the rate of SSRI prescription among stroke patients discharged on antidepressant therapy.

The researchers found that 11% of those who had been prescribed antidepressants had an ICH, compared with 14% of those who had not.

Antidepressant users were more likely to be female; non-Hispanic White; have hypertension; have diabetes; and use oral anticoagulants, antiplatelets, and statins prior to hospital presentation for ICH.

In multivariable analyses adjusting for age, race, prior history of hypertension, diabetes and prior oral anticoagulant, antiplatelet and statin use, antidepressant users were just as likely to present with spontaneous ICH as nonantidepressant users (odds ratio, 0.92; 95% confidence interval, 0.85-1.01).

A total of 3.4% of all ICH patients and 9% of those in whom specific antidepressant information was available were discharged home on an antidepressant, most commonly an SSRI (74%).

The authors noted a key limitation of the study: Some details regarding the length, dosage, and type of antidepressants were not available.
 

Interpret with caution

In a comment, Shaheen Lakhan, MD, PhD, a neurologist in Newton, Mass., and executive director of the Global Neuroscience Initiative Foundation, urged caution in making any firm conclusions based on this study.

“We have two questions here: One, is SSRI use a risk factor for first-time intracerebral hemorrhage, and two, is SSRI use after an ICH a risk factor for additional hemorrhages,” said Dr. Lakhan, who was not involved with the study.

“This study incompletely addresses the first because it is known that SSRIs have a variety of potencies. For instance, paroxetine is a strong inhibitor of serotonin reuptake, whereas bupropion is weak. Hypothetically, the former has a greater risk of ICH. Because this study did not stratify by type of antidepressant, it is not possible to tease these out,” Dr. Lakhan said.

“The second question is completely unaddressed by this study and is the real concern in clinical practice, because the chance of rebleed is much higher than the risk of first-time ICH in the general population,” he added.

The study had no specific funding. Dr. Siddu and Dr. Lakhan disclosed no relevant financial relationships.

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

Stroke, dementias, and migraine cause the most disability among neurological disorders in the United States, according to new findings derived from the 2017 Global Burden of Disease study. 

The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
 

Tracking the burden of neurologic diseases

Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.

The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.

The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.

Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
 

Regional variations

The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”

Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.

Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”

The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
 

Time to adjust the stroke belt?

Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia. 

“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”

Dr. Boehme disclosed no financial conflicts of interest.

Stroke, dementias, and migraine cause the most disability among neurological disorders in the United States, according to new findings derived from the 2017 Global Burden of Disease study. 

The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
 

Tracking the burden of neurologic diseases

Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.

The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.

The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.

Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
 

Regional variations

The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”

Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.

Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”

The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
 

Time to adjust the stroke belt?

Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia. 

“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”

Dr. Boehme disclosed no financial conflicts of interest.

Stroke, dementias, and migraine cause the most disability among neurological disorders in the United States, according to new findings derived from the 2017 Global Burden of Disease study. 

The authors of the analysis, led by Valery Feigin, MD, PhD, of New Zealand’s National Institute for Stroke and Applied Neurosciences, and published in the February 2021 issue of JAMA Neurology, looked at prevalence, incidence, mortality, and disability-adjusted life years for 14 neurological disorders across 50 states between 1990 and 2017. The diseases included in the analysis were stroke, Alzheimer’s disease and other dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, headaches, traumatic brain injury, spinal cord injuries, brain and other nervous system cancers, meningitis, encephalitis, and tetanus.
 

Tracking the burden of neurologic diseases

Dr. Feigin and colleagues estimated that a full 60% of the U.S. population lives with one or more of these disorders, a figure much greater than previous estimates for neurological disease burden nationwide. Tension-type headache and migraine were the most prevalent in the analysis by Dr. Feigin and colleagues. During the study period, they found, prevalence, incidence, and disability burden of nearly all the included disorders increased, with the exception of brain and spinal cord injuries, meningitis, and encephalitis.

The researchers attributed most of the rise in noncommunicable neurological diseases to population aging. An age-standardized analysis found trends for stroke and Alzheimer’s disease and other dementias to be declining or flat. Age-standardized stroke incidence dropped by 16% from 1990 to 2017, while stroke mortality declined by nearly a third, and stroke disability by a quarter. Age-standardized incidence of Alzheimer’s disease and other dementias dropped by 12%, and their prevalence by 13%, during the study period, though dementia mortality and disability were seen increasing.

The authors surmised that the age-standardized declines in stroke and dementias could reflect that “primary prevention of these disorders are beginning to show an influence.” With dementia, which is linked to cognitive reserve and education, “improving educational levels of cohort reaching the age groups at greatest risk of disease may also be contributing to a modest decline over time,” Dr. Feigin and his colleagues wrote.

Parkinson’s disease and multiple sclerosis, meanwhile, were both seen rising in incidence, prevalence, and disability adjusted life years (DALYs) even with age-standardized figures. The United States saw comparatively more disability in 2017 from dementias, Parkinson’s disease, epilepsy, multiple sclerosis, motor neuron disease, and headache disorders, which together comprised 6.7% of DALYs, compared with 4.4% globally; these also accounted for a higher share of mortality in the U.S. than worldwide. The authors attributed at least some of the difference to better case ascertainment in the U.S.
 

Regional variations

The researchers also reported variations in disease burden by state and region. While previous studies have identified a “stroke belt” concentrated in North Carolina, South Carolina, and Georgia, the new findings point to stroke disability highest in Alabama, Arkansas, and Mississippi, and mortality highest in Alabama, Mississippi, and South Carolina. The researchers noted increases in dementia mortality in these states, “likely attributable to the reciprocal association between stroke and dementia.”

Northern states saw higher burdens of multiple sclerosis compared with the rest of the country, while eastern states had higher rates of Parkinson’s disease.

Such regional and state-by state variations, Dr. Feigin and colleagues wrote in their analysis, “may be associated with differences in the case ascertainment, as well as access to health care; racial/ethnic, genetic, and socioeconomic diversity; quality and comprehensiveness of preventive strategies; and risk factor distribution.”

The researchers noted as a limitation of their study that the 14 diseases captured were not an exhaustive list of neurological conditions; chronic lower back pain, a condition included in a previous major study of the burden of neurological disease in the United States, was omitted, as were restless legs syndrome and peripheral neuropathy. The researchers cited changes to coding practice in the U.S. and accuracy of medical claims data as potential limitations of their analysis. The Global Burden of Disease study is funded by the Bill and Melinda Gates Foundation, and several of Dr. Feigin’s coauthors reported financial relationships with industry.
 

Time to adjust the stroke belt?

Amelia Boehme, PhD, a stroke epidemiologist at Columbia University Mailman School of Public Health in New York, said in an interview that the current study added to recent findings showing surprising local variability in stroke prevalence, incidence, and mortality. “What we had always conceptually thought of as the ‘stroke belt’ isn’t necessarily the case,” Dr. Boehme said, but is rather subject to local, county-by-county variations. “Looking at the data here in conjunction with what previous authors have found, it raises some questions as to whether or not state-level data is giving a completely accurate picture, and whether we need to start looking at the county level and adjust for populations and age.” Importantly, Dr. Boehme said, data collected in the Global Burden of Disease study tends to be exceptionally rigorous and systematic, adding weight to Dr. Feigin and colleagues’ suggestions that prevention efforts may be making a dent in stroke and dementia. 

“More data is always needed before we start to say we’re seeing things change,” Dr. Boehme noted. “But any glimmer of optimism is welcome, especially with regard to interventions that have been put in place, to allow us to build on those interventions.”

Dr. Boehme disclosed no financial conflicts of interest.

Restoring movement following a stroke can be challenging, but recent proof-of-concept research may offer an effective way to do just that. Researchers behind the ongoing Cortimo trial successfully performed a procedure on a patient 2 years removed from a stroke, in which microelectrode arrays were implanted into his brain to decode signals driving motor function. These signals then allowed him to operate a powered brace worn on his paralyzed arm.

This news organization spoke with the trial’s principal investigator, Mijail D. Serruya, MD, PhD, an assistant professor of neurology at Thomas Jefferson University Hospital, Philadelphia, about the trial’s initial findings, what this technology may ultimately look like, and the implications for stroke patients in knowing that restorative interventions may be on the horizon.
 

How did you first get involved with implanting electrodes to help stroke patients with recovery?

I was involved in the first human application of a microelectrode array in a young man who had quadriplegia because of a spinal cord injury. We showed that we could record signal directly from his motor cortex and use it to move a cursor on the screen, and open and close a prosthetic hand and arm.

I was naive and thought that this would soon be a widely available clinical medical device. Now it’s nearly 15 years later, and while it certainly has been safely used in multiple labs to record signals from people with spinal cord injury, amyotrophic lateral sclerosis (ALS), or locked-in syndrome from a brain stem stroke, it still requires a team of technicians and a percutaneous connector. It really has not gotten out of the university.

A few years ago I spoke with Robert Rosenwasser, MD, chairman of the department of neurosurgery at Thomas Jefferson, who runs a very busy stroke center and performed the surgery in this trial. We put our heads together and said: “Maybe the time is now to see whether we can move this technology to this much more prevalent condition of a hemispheric stroke.” And that’s what we did.
 

How did the idea of using computer brain electrode interfaces begin?

Around 20 years ago, if you had someone who had severe paralysis and you wanted to restore movement, the question was, where can you get a good control signal from? Obviously, if someone can talk, they can use a voice-actuated system with speech recognition and maybe you can track their eye gaze. But if they’re trying to move their limbs, you want a motor control signal.

In someone who has end-stage ALS or a brain stem stroke, you can’t even record residual muscle activity; you have almost nothing to work with. The only thing left is to try to record directly from the brain itself.

It’s important to clarify that brain-computer interfaces are not necessarily stimulating the brain to inject the signal. They’re just recording the endogenous activity that the brain makes. In comparison, a deep brain stimulator is usually not recording anything; it’s just delivering energy to the brain and hoping for the best.

But what we’re doing is asking, if the person is trying to move the paralyzed limb but can’t, can we get to the source of the signal and then do something with it?
 

What’s the process for measuring that in, for example, someone who has a localized lesion in the motor cortex?

The first step is a scan. People have been doing functional MRI on patients who have had a stroke as long as we’ve had fMRI. We know that people can actually activate on MRI areas of their brain around the stroke, but obviously not in the stroke because it’s been lesioned. However, we do know that the circuit adjacent to it and other regions do appear able to be modulated.

So by having a person either imagine trying to do what they want to do or doing what they can do, if they have some tiny residual movement, you can then identify a kind of hot spot on the fMRI where the brain gobbles up all the oxygen because it’s so active. Then that gives you an anatomical target for the surgeon to place the electrode arrays.
 

The Cortimo trial’s enticing findings

What are the most striking results that you’ve seen so far with the device?

The first thing is that we were able to get such recordings at all. We knew from fMRIs that there were fluctuations in oxygen changing when the person was trying to do something they couldn’t do. But nobody knew that you would see this whole population of individual neurons chattering away when you place these electrode arrays in the motor cortex right next to the stroke, and make sense of what we’re recording.

Obviously, that’s very encouraging and gives us hope that many months or years after a stroke, people’s brains are able to maintain this representation of all these different movements and plans. It’s almost like it’s trapped on the other side of the stroke and some of the signals can’t get out.

The other discovery we’re pleased with is that we can actually decode signals in real time and the person can use it to do something, such as trigger the brain to open and close the hand. That’s very different from all the prior research with brain array interfaces.

Furthermore, the gentleman who participated actually had strokes in other parts of his brain affecting his vision; he had homonymous hemianopia. That raised the question of what happens if you affect parts of the brain that have to do with attention and visual processing. Could a system like this work? And again, the answer appears to be yes.
 

What are the next steps for this technology before it can potentially become available in the clinic?

For this to work, the system clearly has to be fully implantable. What we used was percutaneous. The risk-benefit may be acceptable for someone who has quadriplegia because of, for example, spinal cord injury or end-stage ALS who may already have a tracheostomy and a percutaneous endoscopic gastrostomy. But for someone who is hemiparetic and ambulatory, that may not be acceptable. And a fully implantable system would also have much better patient compliance.

Also, when you’re recording from lots and lots of individual brain cells at many, many samples a second on many, many channels, it’s certainly an engineering challenge. It’s not just a single channel that you occasionally query; it’s hundreds of thousands of channels of this complicated data stream.

But these are solvable challenges. People have been making a lot of progress. It’s really a matter of funding and the engineering expertise, rather than some sort of fundamental scientific breakthrough.

With that said, I think it could be within the next 5-10 years that we could actually have a product that expands the toolbox of what can be done for patients who’ve had a stroke, if they’re motivated and there’s no real contraindication.
 

Creating a novel device

On that point, are you partnering with engineering and technology companies?

The hope is that we and other groups working on this can do for the interface sort of what Celera Genomics did for the Human Genome Project. By having enough interest and investment, you may be able to propel the field forward to widespread use rather than just a purely academic, lab-science type of project.

We are in discussion with different companies to see how we can move ahead with this, and we would be pleased to work with whomever is interested. It may be that different companies have different pieces of the puzzle – a better sensor or a better wireless transmitter.

The plan is to move as quickly as we can to a fully implantable system. And then the benchmark for any kind of clinical advancement is to do a prospective trial. With devices, if you can get a big enough effect size, then you sometimes don’t need quite as many patients to prove it. If paralysis is striking enough and you can reverse that, then you can convince the Food and Drug Administration of its safety and efficacy, and the various insurance companies, that it’s actually reasonable and necessary.
 

How long will an implantable device last?

That’s a key question and concern. If you have someone like our participant, who’s in his early 40s, will it keep working 10, 20, 30, 40 years? For the rest of his life? Deep brain stimulators and cochlear implants do function for those long durations, but their designs are quite different. There’s a macroelectrode that’s just delivering current, which is very different from listening in on this microscopic scale. There are different technical considerations.

One possible solution is to make the device out of living tissue, which is something I just wrote about with my colleague D. Kacy Cullen. Living electrodes and amplifiers may seem a bit like science fiction, but on the other hand, we have over a century of plastic surgeons, neurosurgeons, and orthopedic surgeons doing all kinds of complicated modifications of the body, moving nerves and vessels around. It makes you realize that, in a sense, they’ve already done living electrodes by doing a nerve transfer. So the question becomes whether we can refine that living electrode technology, which could then open up more possibilities.
 

Are there any final messages you’d like to share with clinician audience of this news organization?

Regardless of our specialty, we’re always telling our patients about the benefits of things like eating healthy, exercise, and sleep. Now we can point to the fact that, 2 years after stroke, all of these brain areas are still active, and devices that can potentially reverse and unparalyze your limbs may be available in the coming 5- or 10-plus years. That gives clinicians more justification to tell their patients to really stay on top of those things so that they can be in as optimal brain-mind health as possible to someday benefit from them.

Patients and their families need to be part of the conversation of where this is all going. That’s one thing that’s totally different for brain devices versus other devices, where a person’s psychological state doesn’t necessarily matter. But with a brain device, your mental state, psychosocial situation, exercise, sleep – the way you think about and approach it – actually changes to the structure of the brain pretty dramatically.

I don’t want to cause unreasonable hope that we’re going to snap our fingers and it’s going to be cured. But I do think it’s fair to raise a possibility as a way to say that keeping oneself really healthy is justified.

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

Restoring movement following a stroke can be challenging, but recent proof-of-concept research may offer an effective way to do just that. Researchers behind the ongoing Cortimo trial successfully performed a procedure on a patient 2 years removed from a stroke, in which microelectrode arrays were implanted into his brain to decode signals driving motor function. These signals then allowed him to operate a powered brace worn on his paralyzed arm.

This news organization spoke with the trial’s principal investigator, Mijail D. Serruya, MD, PhD, an assistant professor of neurology at Thomas Jefferson University Hospital, Philadelphia, about the trial’s initial findings, what this technology may ultimately look like, and the implications for stroke patients in knowing that restorative interventions may be on the horizon.
 

How did you first get involved with implanting electrodes to help stroke patients with recovery?

I was involved in the first human application of a microelectrode array in a young man who had quadriplegia because of a spinal cord injury. We showed that we could record signal directly from his motor cortex and use it to move a cursor on the screen, and open and close a prosthetic hand and arm.

I was naive and thought that this would soon be a widely available clinical medical device. Now it’s nearly 15 years later, and while it certainly has been safely used in multiple labs to record signals from people with spinal cord injury, amyotrophic lateral sclerosis (ALS), or locked-in syndrome from a brain stem stroke, it still requires a team of technicians and a percutaneous connector. It really has not gotten out of the university.

A few years ago I spoke with Robert Rosenwasser, MD, chairman of the department of neurosurgery at Thomas Jefferson, who runs a very busy stroke center and performed the surgery in this trial. We put our heads together and said: “Maybe the time is now to see whether we can move this technology to this much more prevalent condition of a hemispheric stroke.” And that’s what we did.
 

How did the idea of using computer brain electrode interfaces begin?

Around 20 years ago, if you had someone who had severe paralysis and you wanted to restore movement, the question was, where can you get a good control signal from? Obviously, if someone can talk, they can use a voice-actuated system with speech recognition and maybe you can track their eye gaze. But if they’re trying to move their limbs, you want a motor control signal.

In someone who has end-stage ALS or a brain stem stroke, you can’t even record residual muscle activity; you have almost nothing to work with. The only thing left is to try to record directly from the brain itself.

It’s important to clarify that brain-computer interfaces are not necessarily stimulating the brain to inject the signal. They’re just recording the endogenous activity that the brain makes. In comparison, a deep brain stimulator is usually not recording anything; it’s just delivering energy to the brain and hoping for the best.

But what we’re doing is asking, if the person is trying to move the paralyzed limb but can’t, can we get to the source of the signal and then do something with it?
 

What’s the process for measuring that in, for example, someone who has a localized lesion in the motor cortex?

The first step is a scan. People have been doing functional MRI on patients who have had a stroke as long as we’ve had fMRI. We know that people can actually activate on MRI areas of their brain around the stroke, but obviously not in the stroke because it’s been lesioned. However, we do know that the circuit adjacent to it and other regions do appear able to be modulated.

So by having a person either imagine trying to do what they want to do or doing what they can do, if they have some tiny residual movement, you can then identify a kind of hot spot on the fMRI where the brain gobbles up all the oxygen because it’s so active. Then that gives you an anatomical target for the surgeon to place the electrode arrays.
 

The Cortimo trial’s enticing findings

What are the most striking results that you’ve seen so far with the device?

The first thing is that we were able to get such recordings at all. We knew from fMRIs that there were fluctuations in oxygen changing when the person was trying to do something they couldn’t do. But nobody knew that you would see this whole population of individual neurons chattering away when you place these electrode arrays in the motor cortex right next to the stroke, and make sense of what we’re recording.

Obviously, that’s very encouraging and gives us hope that many months or years after a stroke, people’s brains are able to maintain this representation of all these different movements and plans. It’s almost like it’s trapped on the other side of the stroke and some of the signals can’t get out.

The other discovery we’re pleased with is that we can actually decode signals in real time and the person can use it to do something, such as trigger the brain to open and close the hand. That’s very different from all the prior research with brain array interfaces.

Furthermore, the gentleman who participated actually had strokes in other parts of his brain affecting his vision; he had homonymous hemianopia. That raised the question of what happens if you affect parts of the brain that have to do with attention and visual processing. Could a system like this work? And again, the answer appears to be yes.
 

What are the next steps for this technology before it can potentially become available in the clinic?

For this to work, the system clearly has to be fully implantable. What we used was percutaneous. The risk-benefit may be acceptable for someone who has quadriplegia because of, for example, spinal cord injury or end-stage ALS who may already have a tracheostomy and a percutaneous endoscopic gastrostomy. But for someone who is hemiparetic and ambulatory, that may not be acceptable. And a fully implantable system would also have much better patient compliance.

Also, when you’re recording from lots and lots of individual brain cells at many, many samples a second on many, many channels, it’s certainly an engineering challenge. It’s not just a single channel that you occasionally query; it’s hundreds of thousands of channels of this complicated data stream.

But these are solvable challenges. People have been making a lot of progress. It’s really a matter of funding and the engineering expertise, rather than some sort of fundamental scientific breakthrough.

With that said, I think it could be within the next 5-10 years that we could actually have a product that expands the toolbox of what can be done for patients who’ve had a stroke, if they’re motivated and there’s no real contraindication.
 

Creating a novel device

On that point, are you partnering with engineering and technology companies?

The hope is that we and other groups working on this can do for the interface sort of what Celera Genomics did for the Human Genome Project. By having enough interest and investment, you may be able to propel the field forward to widespread use rather than just a purely academic, lab-science type of project.

We are in discussion with different companies to see how we can move ahead with this, and we would be pleased to work with whomever is interested. It may be that different companies have different pieces of the puzzle – a better sensor or a better wireless transmitter.

The plan is to move as quickly as we can to a fully implantable system. And then the benchmark for any kind of clinical advancement is to do a prospective trial. With devices, if you can get a big enough effect size, then you sometimes don’t need quite as many patients to prove it. If paralysis is striking enough and you can reverse that, then you can convince the Food and Drug Administration of its safety and efficacy, and the various insurance companies, that it’s actually reasonable and necessary.
 

How long will an implantable device last?

That’s a key question and concern. If you have someone like our participant, who’s in his early 40s, will it keep working 10, 20, 30, 40 years? For the rest of his life? Deep brain stimulators and cochlear implants do function for those long durations, but their designs are quite different. There’s a macroelectrode that’s just delivering current, which is very different from listening in on this microscopic scale. There are different technical considerations.

One possible solution is to make the device out of living tissue, which is something I just wrote about with my colleague D. Kacy Cullen. Living electrodes and amplifiers may seem a bit like science fiction, but on the other hand, we have over a century of plastic surgeons, neurosurgeons, and orthopedic surgeons doing all kinds of complicated modifications of the body, moving nerves and vessels around. It makes you realize that, in a sense, they’ve already done living electrodes by doing a nerve transfer. So the question becomes whether we can refine that living electrode technology, which could then open up more possibilities.
 

Are there any final messages you’d like to share with clinician audience of this news organization?

Regardless of our specialty, we’re always telling our patients about the benefits of things like eating healthy, exercise, and sleep. Now we can point to the fact that, 2 years after stroke, all of these brain areas are still active, and devices that can potentially reverse and unparalyze your limbs may be available in the coming 5- or 10-plus years. That gives clinicians more justification to tell their patients to really stay on top of those things so that they can be in as optimal brain-mind health as possible to someday benefit from them.

Patients and their families need to be part of the conversation of where this is all going. That’s one thing that’s totally different for brain devices versus other devices, where a person’s psychological state doesn’t necessarily matter. But with a brain device, your mental state, psychosocial situation, exercise, sleep – the way you think about and approach it – actually changes to the structure of the brain pretty dramatically.

I don’t want to cause unreasonable hope that we’re going to snap our fingers and it’s going to be cured. But I do think it’s fair to raise a possibility as a way to say that keeping oneself really healthy is justified.

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

Restoring movement following a stroke can be challenging, but recent proof-of-concept research may offer an effective way to do just that. Researchers behind the ongoing Cortimo trial successfully performed a procedure on a patient 2 years removed from a stroke, in which microelectrode arrays were implanted into his brain to decode signals driving motor function. These signals then allowed him to operate a powered brace worn on his paralyzed arm.

This news organization spoke with the trial’s principal investigator, Mijail D. Serruya, MD, PhD, an assistant professor of neurology at Thomas Jefferson University Hospital, Philadelphia, about the trial’s initial findings, what this technology may ultimately look like, and the implications for stroke patients in knowing that restorative interventions may be on the horizon.
 

How did you first get involved with implanting electrodes to help stroke patients with recovery?

I was involved in the first human application of a microelectrode array in a young man who had quadriplegia because of a spinal cord injury. We showed that we could record signal directly from his motor cortex and use it to move a cursor on the screen, and open and close a prosthetic hand and arm.

I was naive and thought that this would soon be a widely available clinical medical device. Now it’s nearly 15 years later, and while it certainly has been safely used in multiple labs to record signals from people with spinal cord injury, amyotrophic lateral sclerosis (ALS), or locked-in syndrome from a brain stem stroke, it still requires a team of technicians and a percutaneous connector. It really has not gotten out of the university.

A few years ago I spoke with Robert Rosenwasser, MD, chairman of the department of neurosurgery at Thomas Jefferson, who runs a very busy stroke center and performed the surgery in this trial. We put our heads together and said: “Maybe the time is now to see whether we can move this technology to this much more prevalent condition of a hemispheric stroke.” And that’s what we did.
 

How did the idea of using computer brain electrode interfaces begin?

Around 20 years ago, if you had someone who had severe paralysis and you wanted to restore movement, the question was, where can you get a good control signal from? Obviously, if someone can talk, they can use a voice-actuated system with speech recognition and maybe you can track their eye gaze. But if they’re trying to move their limbs, you want a motor control signal.

In someone who has end-stage ALS or a brain stem stroke, you can’t even record residual muscle activity; you have almost nothing to work with. The only thing left is to try to record directly from the brain itself.

It’s important to clarify that brain-computer interfaces are not necessarily stimulating the brain to inject the signal. They’re just recording the endogenous activity that the brain makes. In comparison, a deep brain stimulator is usually not recording anything; it’s just delivering energy to the brain and hoping for the best.

But what we’re doing is asking, if the person is trying to move the paralyzed limb but can’t, can we get to the source of the signal and then do something with it?
 

What’s the process for measuring that in, for example, someone who has a localized lesion in the motor cortex?

The first step is a scan. People have been doing functional MRI on patients who have had a stroke as long as we’ve had fMRI. We know that people can actually activate on MRI areas of their brain around the stroke, but obviously not in the stroke because it’s been lesioned. However, we do know that the circuit adjacent to it and other regions do appear able to be modulated.

So by having a person either imagine trying to do what they want to do or doing what they can do, if they have some tiny residual movement, you can then identify a kind of hot spot on the fMRI where the brain gobbles up all the oxygen because it’s so active. Then that gives you an anatomical target for the surgeon to place the electrode arrays.
 

The Cortimo trial’s enticing findings

What are the most striking results that you’ve seen so far with the device?

The first thing is that we were able to get such recordings at all. We knew from fMRIs that there were fluctuations in oxygen changing when the person was trying to do something they couldn’t do. But nobody knew that you would see this whole population of individual neurons chattering away when you place these electrode arrays in the motor cortex right next to the stroke, and make sense of what we’re recording.

Obviously, that’s very encouraging and gives us hope that many months or years after a stroke, people’s brains are able to maintain this representation of all these different movements and plans. It’s almost like it’s trapped on the other side of the stroke and some of the signals can’t get out.

The other discovery we’re pleased with is that we can actually decode signals in real time and the person can use it to do something, such as trigger the brain to open and close the hand. That’s very different from all the prior research with brain array interfaces.

Furthermore, the gentleman who participated actually had strokes in other parts of his brain affecting his vision; he had homonymous hemianopia. That raised the question of what happens if you affect parts of the brain that have to do with attention and visual processing. Could a system like this work? And again, the answer appears to be yes.
 

What are the next steps for this technology before it can potentially become available in the clinic?

For this to work, the system clearly has to be fully implantable. What we used was percutaneous. The risk-benefit may be acceptable for someone who has quadriplegia because of, for example, spinal cord injury or end-stage ALS who may already have a tracheostomy and a percutaneous endoscopic gastrostomy. But for someone who is hemiparetic and ambulatory, that may not be acceptable. And a fully implantable system would also have much better patient compliance.

Also, when you’re recording from lots and lots of individual brain cells at many, many samples a second on many, many channels, it’s certainly an engineering challenge. It’s not just a single channel that you occasionally query; it’s hundreds of thousands of channels of this complicated data stream.

But these are solvable challenges. People have been making a lot of progress. It’s really a matter of funding and the engineering expertise, rather than some sort of fundamental scientific breakthrough.

With that said, I think it could be within the next 5-10 years that we could actually have a product that expands the toolbox of what can be done for patients who’ve had a stroke, if they’re motivated and there’s no real contraindication.
 

Creating a novel device

On that point, are you partnering with engineering and technology companies?

The hope is that we and other groups working on this can do for the interface sort of what Celera Genomics did for the Human Genome Project. By having enough interest and investment, you may be able to propel the field forward to widespread use rather than just a purely academic, lab-science type of project.

We are in discussion with different companies to see how we can move ahead with this, and we would be pleased to work with whomever is interested. It may be that different companies have different pieces of the puzzle – a better sensor or a better wireless transmitter.

The plan is to move as quickly as we can to a fully implantable system. And then the benchmark for any kind of clinical advancement is to do a prospective trial. With devices, if you can get a big enough effect size, then you sometimes don’t need quite as many patients to prove it. If paralysis is striking enough and you can reverse that, then you can convince the Food and Drug Administration of its safety and efficacy, and the various insurance companies, that it’s actually reasonable and necessary.
 

How long will an implantable device last?

That’s a key question and concern. If you have someone like our participant, who’s in his early 40s, will it keep working 10, 20, 30, 40 years? For the rest of his life? Deep brain stimulators and cochlear implants do function for those long durations, but their designs are quite different. There’s a macroelectrode that’s just delivering current, which is very different from listening in on this microscopic scale. There are different technical considerations.

One possible solution is to make the device out of living tissue, which is something I just wrote about with my colleague D. Kacy Cullen. Living electrodes and amplifiers may seem a bit like science fiction, but on the other hand, we have over a century of plastic surgeons, neurosurgeons, and orthopedic surgeons doing all kinds of complicated modifications of the body, moving nerves and vessels around. It makes you realize that, in a sense, they’ve already done living electrodes by doing a nerve transfer. So the question becomes whether we can refine that living electrode technology, which could then open up more possibilities.
 

Are there any final messages you’d like to share with clinician audience of this news organization?

Regardless of our specialty, we’re always telling our patients about the benefits of things like eating healthy, exercise, and sleep. Now we can point to the fact that, 2 years after stroke, all of these brain areas are still active, and devices that can potentially reverse and unparalyze your limbs may be available in the coming 5- or 10-plus years. That gives clinicians more justification to tell their patients to really stay on top of those things so that they can be in as optimal brain-mind health as possible to someday benefit from them.

Patients and their families need to be part of the conversation of where this is all going. That’s one thing that’s totally different for brain devices versus other devices, where a person’s psychological state doesn’t necessarily matter. But with a brain device, your mental state, psychosocial situation, exercise, sleep – the way you think about and approach it – actually changes to the structure of the brain pretty dramatically.

I don’t want to cause unreasonable hope that we’re going to snap our fingers and it’s going to be cured. But I do think it’s fair to raise a possibility as a way to say that keeping oneself really healthy is justified.

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