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Tenecteplase for stroke thrombolysis up to 24 hours?
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
, a new trial from China suggests.
The phase 2a CHABLIS trial was presented at the International Stroke Conference by Xin Cheng, MD, associate professor of neurology at the Huashan Hospital of Fudan University and the National Center for Neurological Disorders in Shanghai, China.
“These results are the first to be reported with tenecteplase in the extended time window and suggest that it may be feasible to extend the time window of intravenous thrombolysis to 24 hours after last known well through perfusion imaging selection,” she concluded at the conference presented by the American Stroke Association, a division of the American Heart Association.
Dr. Cheng noted that alteplase (tissue plasminogen activator) is the standard of care for thrombolysis in stroke, with a time window of up to 4.5 hours after stroke onset. However, the recent EXTEND trial suggested benefit of alteplase in patients who were between 4.5 and 9 hours of stroke onset and who had hypoperfused but salvageable regions of brain detected on automated perfusion imaging.
Tenecteplase is a genetically modified variant of alteplase. It has received regulatory approval for treatment of myocardial infarction. Dr. Cheng said there is increasing interest in tenecteplase as an alternative to alteplase, mainly because of its practical advantages (single bolus, rather than 1-hour infusion) and its having a number of hypothetical advantages over alteplase, including greater fibrin specificity and lesser likelihood of fibrinogen depletion.
Until now, studies of tenecteplase in stroke have included patients in the traditional time window, which has been no longer than 6 hours from stroke onset, she added.
For the current CHABLIS trial, the Chinese researchers investigated the use of tenecteplase administered to ischemic stroke patients at 4.5-24 hours from time of their being last seen well who were selected by significant penumbral mismatch on perfusion imaging. The trial included 86 patients who had an anterior large-vessel occlusion or severe stenosis identified on head and neck CT angiography and penumbral mismatch on CT perfusion imaging. They were randomized to one of two doses of tenecteplase, 0.25 mg/kg or 0.32 mg/kg.
The primary outcome was the achievement of reperfusion without symptomatic intracranial hemorrhage at 24-48 hours after thrombolysis. This occurred in 32% of the 0.25-mg/kg group versus 23.3% of the 0.32-mg/kg group.
Recanalization at 4-6 hours occurred in 44% of both groups.
In terms of neurologic outcomes, an excellent functional outcome, defined as a Modified Rankin Scale (mRS) score of 0-1 at 90 days, was achieved in 28% of the 0.25-mg/kg group and 49% of the 0.32-mg/kg group. A good functional outcome (mRS, 0-2) occurred in 46% of the 0.25-mg/kg group versus 60% of the 0.32-mg/kg group.
Limitations of the study included a small sample size and the lack of a control group. In addition, the study included only Chinese patients, who are known to have different stroke etiologies in comparison with White patients, Dr. Cheng noted.
In the subset of patients who received tenecteplase and who underwent endovascular therapy, fewer patients (8.8%) reached the primary outcome measure of reperfusion without symptomatic ICH, compared with those who received only tenecteplase (40.4%).
“In our study, tenecteplase seems to be quite effective and safe in patients who do not need endovascular therapy,” Dr. Cheng said. “More research is needed to understand why tenecteplase was less effective in restoring blood flow and more likely to result in symptomatic brain bleeding among those who had endovascular therapy.”
The researchers have now started a phase 2b trial, CHABLIS-2. This is a randomized, multicenter, controlled, open-label study of the 0.25-mg/kg dose of tenecteplase.
Commenting on the current study at an ISC press conference, Tudor G. Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “This is very important study looking at the question of using thrombolysis out to 24 hours, and it does suggest a benefit, but we don’t know the best dose yet.”
He noted that his hospital system has already switched from alteplase to tenecteplase in the treatment of stroke, and several other centers are also making this switch. “In our center, we use the 0.25-mg/kg dose, but we don’t routinely treat patients beyond the 4.5-hour time window,” Dr. Jovin reported.
“The signals are there for a longer treatment window,” he said. “But this study was not aiming to directly answer whether tenecteplase is better than no treatment or alteplase, or its use with endovascular therapy.”
Noting that there are similar randomized trials ongoing in the United States and other countries exploring the same doses of tenecteplase, he said he thought the “dose and approach is applicable to U.S. practice.”
The CHABLIS study was funded by national key research and development program of China from the Science and Technology Ministry. Tenecteplase was provided by Guangzhou Recomgen Biotech.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
DOACs comparable to warfarin in CVT
and are less likely to result in major bleeding, a retrospective study suggests.
The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.
It was also simultaneously published online in Stroke.
“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.
But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.
Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.
Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.
She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.
A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.
A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.
As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.
The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.
The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.
The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.
The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.
The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.
Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.
Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.
When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).
But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).
When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
Similar efficacy, better safety
Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”
Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”
“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”
In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”
They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”
They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”
The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.
The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.
A version of this article first appeared on Medscape.com.
and are less likely to result in major bleeding, a retrospective study suggests.
The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.
It was also simultaneously published online in Stroke.
“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.
But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.
Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.
Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.
She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.
A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.
A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.
As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.
The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.
The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.
The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.
The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.
The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.
Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.
Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.
When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).
But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).
When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
Similar efficacy, better safety
Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”
Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”
“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”
In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”
They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”
They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”
The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.
The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.
A version of this article first appeared on Medscape.com.
and are less likely to result in major bleeding, a retrospective study suggests.
The ACTION CVT study was presented at the International Stroke Conference (ISC) 2022 by Ekaterina Bakradze, MD, assistant professor of neurology at the University of Alabama at Birmingham.
It was also simultaneously published online in Stroke.
“This real-world data supports use of direct oral anticoagulant drugs as a reasonable alternative to warfarin in patients with cerebral venous thrombosis,” Dr. Bakradze concluded.
But she added that because this study was based on retrospective observational data, the findings should be interpreted with caution and require confirmation by larger prospective studies.
Two such studies are now underway: the Direct Oral Anticoagulants in the Treatment of Cerebral Venous Thrombosis (DOAC-CVT) study and the randomized Study of Rivaroxaban for Cerebral Venous Thrombosis (SECRET) trial.
Dr. Bakradze explained that cerebral venous thrombosis is a less common cause of stroke and occurs more often in women and younger patients, with a median age of 37 years. Current recommended treatment consists of heparin followed by oral anticoagulation.
She noted that although randomized trials and current guidelines indicate that DOACs are a preferred alternative to warfarin for the treatment of patients with venous thromboembolism, there are limited data on their use in patients with CVT.
A small, randomized trial (RESPECT-CVT) showed no significant difference in efficacy and safety outcomes between dabigatran and warfarin in patients with cerebral venous thrombosis, but with only 120 patients, this trial was too small for definite answers to this question.
A better understanding of this issue is important, because the mechanisms underlying cerebral venous thrombosis and other thromboembolism and their subsequent risks may differ, Dr. Bakradze said.
As randomized trials in patients with cerebral venous thrombosis are difficult to perform because the condition has a low incidence and low event rates, the researchers decided to look at this question with a large retrospective multicenter study.
The ACTION-CVT study involved 845 consecutive patients with cerebral venous thrombosis over 6 years (from January 2015 and December 2020) from 27 centers in Italy, New Zealand, Switzerland, and the United States. Patients were identified from medical records with diagnostic codes and confirmed with imaging.
The primary predictor in the study was oral anticoagulant type (DOAC vs. warfarin). Study outcomes were abstracted by individual sites through review of all available medical records.
The primary outcome was recurrent venous thrombosis (venous thromboembolism or cerebral venous thrombosis) during follow-up. Imaging outcomes based on recanalization status on last venous imaging study abstracted from radiology reports were also reported.
The safety outcome was major hemorrhage, defined as new or worsening intracranial hemorrhage (ICH), or major extracranial hemorrhage. Results were adjusted for age, sex, and relevant medical conditions.
The mean age of the patients included was 44.8 years, 64.7% were women, 33% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times.
Results showed that during a median follow-up of 345 days, there were 5.68 recurrent venous thrombosis events, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years.
Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization.
When compared with warfarin, DOAC treatment was associated with similar risk for recurrent venous thrombosis (adjusted hazard ratio, 0.94; 95% confidence interval, 0.51-1.73; P = .84), death (aHR, 0.71, 95% CI, 0.24-2.08; P = .53), and rate of partial/complete recanalization (aHR, 0.92, 95% CI, 0.48-1.73; P = .79).
But patients who received a DOAC had a significantly lower rate of major hemorrhage (aHR, 0.35; 95% CI, 0.15-0.81; P = .02).
When examined separately, the occurrence of ICH per 100 patient-years was much lower among the patients prescribed DOACs than those who were prescribed warfarin (1.52 vs. 3.51), whereas the occurrence of major bleeding outside the brain was similar (0.91 vs. 1.15).
Similar efficacy, better safety
Commenting on the study at an ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association and professor of neurology at Columbia University, New York, said: “The community has been concerned about extending the use of these new direct-acting oral anticoagulant drugs to cerebral venous thrombosis, but this study suggests that these patients may benefit from these new agents too.”
Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, also commented: “This study confirms what we already know from other indications about these DOAC drugs: that they have similar efficacy to warfarin but a better safety profile. These results are really spot on with that. These drugs are also much easier and more convenient to use than warfarin.”
“This is a great step forward,” he added. “Only 30% of patients in this study received DOACs, reflecting the fact that clinicians may be a little reluctant to use them in this condition. But this study now has the potential to change practice.”
In an editorial accompanying the publication in Stroke, Johnathon Gorman, MD, and Thalia Field, MD, from the Vancouver Stroke Program at the University of British Columbia, say that despite its methodological limitations, the ACTION-CVT study “provides added value to the current state of knowledge by virtue of its size and ‘real world’ setting that is reflective of how DOACs are being used to manage CVT in current clinical practice.”
They point out that although baseline characteristics between the DOAC and warfarin groups were similar, the possibility of confounding cannot be excluded, and “other characteristics not easily captured in a retrospective study may sway anticoagulation strategy.”
They acknowledge, however, that an additional propensity score analysis “provides reassurance that the groups are reasonably balanced, adjusting for variables associated with recurrent cerebral venous thrombosis, recanalization, and hemorrhage.”
The editorialists conclude that ACTION-CVT gives additional reassurance for DOACs as an alternative approach to warfarin as a treatment for cerebral venous thrombosis and for the shifts in clinical practice that are already occurring at many centers.
The study was partially supported by the Italian Ministry of Health Ricerca Corrente–IRCCS MultiMedica. Dr. Bakradze reports no disclosures. Dr. Field is the principal investigator of the SECRET trial, which received in-kind study medication from Bayer Canada. She reports honoraria from HLS Therapeutics outside the submitted work and is on the board of Destine Health. The other editorialist reports no conflicts.
A version of this article first appeared on Medscape.com.
From ISC 2022
Can periodontal treatment reduce cardiovascular events in stroke patients?
The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.
The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.
Both groups had a much lower event rate compared with a historical control group made up of similar patients.
In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.
“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.
“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”
Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.
“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.
“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.
Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.
For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.
Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.
The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.
All patients received comprehensive conventional stroke risk factor treatment.
The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.
Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).
But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.
In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.
Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.
Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.
A new part of routine post-stroke care?
“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.
He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”
Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.
“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”
“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.
But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.
“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
‘Promising’ results
Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.
“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”
The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).
A version of this article first appeared on Medscape.com.
The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.
The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.
Both groups had a much lower event rate compared with a historical control group made up of similar patients.
In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.
“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.
“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”
Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.
“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.
“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.
Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.
For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.
Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.
The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.
All patients received comprehensive conventional stroke risk factor treatment.
The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.
Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).
But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.
In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.
Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.
Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.
A new part of routine post-stroke care?
“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.
He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”
Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.
“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”
“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.
But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.
“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
‘Promising’ results
Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.
“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”
The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).
A version of this article first appeared on Medscape.com.
The first randomized trial to investigate whether periodontal treatment can reduce future risk of cardiovascular events or stroke suggests some promise with this strategy.
The PREMIERS study, which was conducted in patients with a recent stroke or transient ischemic attack (TIA) who also had gum disease, did not show a statistically significant difference between intensive periodontal treatment and standard treatment in the rate of recurrent stroke, myocardial infarction (MI), or death in the 1-year follow-up, although there was a strong trend toward benefit in the intensive group.
Both groups had a much lower event rate compared with a historical control group made up of similar patients.
In addition, the number of dental visits significantly correlated with a reduction in the composite event rate in the study.
“My take-home message from this study is that periodontal treatment does appear to impact cardiovascular outcomes in stroke/TIA patients,” said lead author Souvik Sen, MD, MPH, professor of neurology at the University of South Carolina School of Medicine.
“Even standard periodontal care – a dental cleaning every 3 months – was beneficial.”
Dr. Sen presented the study at the hybrid International Stroke Conference (ISC), taking place in New Orleans and virtually.
“This was a very ambitious study, and it turned out to be very underpowered for the comparisons involved, but I was impressed that we saw such a strong trend toward benefit in the intensive group,” he said at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Dr. Sen explained that they initially set out to compare periodontal treatment with no treatment, but they were unable to have a control group who received no treatment for ethical reasons, so they ended up comparing standard treatment with intensive treatment.
“We probably needed a study of twice the size for that comparison. But our results are encouraging, and we now plan to do a larger study,” he said.
Dr. Sen reported that gum disease (periodontitis) is extremely prevalent, occurring in around half the U.S. population. It is particularly prevalent in the southeastern part of the United States, known as the “Stroke Belt” because of a much higher incidence of stroke compared with the rest of the country. Gum disease is known to be associated with an increased risk of cardiovascular events and stroke.
For the study, 280 patients from the Stroke Belt area with a recent stroke or TIA and periodontal disease were randomly assigned to standard periodontal treatment or intensive periodontal treatment and followed for 1 year.
Standard treatment was composed of regular (every 3 months) supragingival removal of plaque and calculus; patients were also given a regular toothbrush and advice about dental care.
The intensive group received supragingival and subgingival removal of plaque and calculus (also every 3 months), extraction of hopeless teeth, locally delivered antibiotics. In addition, patients were given an electric toothbrush, mouthwash, and an air flosser for dental care.
All patients received comprehensive conventional stroke risk factor treatment.
The study had an adaptive randomization design to ensure both groups were balanced in terms of age, stroke causes, race, socioeconomic status, and stroke risk factors.
Results showed that after 1 year of follow-up, the primary outcome (stroke/myocardial infarction/death) had occurred in 7.7% of the intensive treatment group versus 12.3% of the standard care group, giving a hazard ratio of 0.65 (95% confidence interval, 0.30-1.38; P = .26).
But both groups had a much lower rate of recurrent events, compared with a historical control group which showed a 1-year rate of stroke/MI/death of 24%. The historical controls were part of an observational study that the same group of researchers conducted previously in a similar population.
In both standard treatment and intensive treatment groups, the combined number of dental visits strongly correlated with a reduction in cardiovascular events. Of the study participants, 65% attended all five visits, 25% attended two to four, and 10% did not attend any after the baseline assessment.
Those who attended all visits in the year had a rate of stroke/MI/death at 1 year of 8%. And those who did not attend any further visits after the baseline visit had an event rate of 25% at 1-year follow-up, which Dr. Sen noted was very similar to that of the historical controls. The P value for this trend was “very significant” (P = .0017), he said.
Secondary outcomes showed a reduction in blood pressure, A1c levels, carotid intima-media thickness, and better lipid profiles in all patients who underwent treatment – in both standard treatment and intensive treatment.
A new part of routine post-stroke care?
“Previous data on how gum disease and periodontal treatment relates to cardiovascular outcomes have all come from observational studies. They have shown that regular dental care is associated with reduced incidence of future cardiovascular events. But until now, we haven’t had any randomized data,” Dr. Sen noted.
He believes advice on oral and dental care should be part of routine clinical practice for patients who have suffered stroke. “This is not something we currently think about, but it could make a big difference in future event rates.”
Dr. Sen said the current study had raised interest in the topic, and his presentation was received with enthusiasm from the audience.
“We are in South Carolina in the Stroke Belt. Previous studies have shown that gum disease is very prevalent in this area. People in this area have a high risk of stroke, but we don’t know all the attributable risk factors. The traditional stroke risk factors do not seem to account for all the excess risk,” Dr. Sen said. “Periodontal disease could be one of the additional risk factors that accounts for the increased stroke risk in this population.”
“I believe doctors treating stroke patients should advise that they pay particular attention to oral care and visit the dentist frequently for periodontal treatment if they have gum disease. It is very unusual for people to get regular dental cleaning. They don’t understand that they need to do this,” he said.
But he acknowledges that larger studies are needed to show statistically significant results to be able to achieve a strong recommendation in the secondary prevention clinical guidelines.
“Even in individuals who haven’t had a stroke or cardiovascular event, population-based observational studies clearly show that gum infection is linked to future risk of myocardial infarction and stroke and that regular dental care (one or more visits per year) can reduce this risk. I don’t think we can do a randomized trial in the general population – that would need enormous numbers. We will have to rely on the observational studies here,” he added.
‘Promising’ results
Commenting on the current study, Louise McCullough, MD, ISC 2022 program chair, said she thought the results were promising.
“There was no difference in the intensive cleaning group versus standard cleaning, but the number of events was small, so it was underpowered to see differences. I think the main take home point is that both groups that came for dental visits had a much lower risk of another event than the group that did not show up for follow-up,” said Dr. McCullough, chair of the department of neurology, McGovern Medical School, University of Texas Health Science Center, Houston. “Clearly, seeing a provider made a difference. It is likely that contact with a dentist, getting blood pressure checked, etc., made a dramatic difference.”
The study was funded by the National Institute of Minority Health Disparity, Phillips Oral Healthcare, and Orapharma (which provided the study antibiotic medication).
A version of this article first appeared on Medscape.com.
FROM ISC 2022
‘Remarkable’ benefit with intra-arterial tPA after stroke thrombectomy: CHOICE
in a new study.
The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.
The study was also published online in JAMA to coincide with the presentation at the ISC.
The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.
This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”
He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.
The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
‘Dramatic and exciting results’
The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”
“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”
And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”
Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”
But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
An abbreviated phase 2b trial
The CHOICE trial was conducted in seven centers in Catalonia, Spain.
For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.
Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.
Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).
The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).
Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).
The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.
He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.
In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.
“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.
Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.
In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”
However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.
But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”
Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.
Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.
A version of this article first appeared on Medscape.com.
in a new study.
The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.
The study was also published online in JAMA to coincide with the presentation at the ISC.
The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.
This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”
He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.
The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
‘Dramatic and exciting results’
The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”
“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”
And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”
Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”
But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
An abbreviated phase 2b trial
The CHOICE trial was conducted in seven centers in Catalonia, Spain.
For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.
Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.
Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).
The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).
Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).
The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.
He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.
In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.
“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.
Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.
In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”
However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.
But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”
Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.
Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.
A version of this article first appeared on Medscape.com.
in a new study.
The phase 2b CHOICE study was presented at the International Stroke Conference by Ángel Chamorro, MD, University of Barcelona, who received a round of applause as the results were revealed.
The study was also published online in JAMA to coincide with the presentation at the ISC.
The main results showed a remarkable and significant 18.4% absolute increase in the number of patients achieving an excellent neurologic outcome, defined as modified Rankin Scale (mRS) score of 0-1, after treatment with intra-arterial alteplase immediately following thrombectomy. This was despite the fact that the study was stopped early because of difficulty obtaining placebo supplies during the pandemic, having only enrolled 121 of the planned 200 patients.
This benefit was achieved without any increase in intracranial hemorrhage, which Dr. Chamorro described as “reassuring.”
He explained that although mechanical thrombectomy gives a high rate of successful reperfusion, only about 27% of patients achieve complete freedom of disability (mRS 0-1) at 3 months. He suggested that this may be the result of impaired reperfusion of the microcirculation despite complete recanalization of the occluded vessel.
The researchers postulated that thrombi could persist within the microcirculation in patients with normal or nearly normal cerebral angiograms at the end of thrombectomy and that these smaller thrombi may be dissolved by a dose of intra-arterial thrombolysis.
‘Dramatic and exciting results’
The CHOICE study was greeted with enthusiasm from commentators at the ISC meeting, which was presented by the American Stroke Association, a division of the American Heart Association. Louise McCullough, MD, chair of the late-breaking science session at which the study was presented and ISC program chair, described the results as “very dramatic and very exciting.”
“The CHOICE trial is going to be a highlight of the meeting because it could change care now,” Dr. McCullough said. “By just giving a little adjunctive tPA after the main clot is out, everybody seems to benefit, and there was no increased risk in bleeding. I think that’s the one that people are going to take back to their practice. But it was a very small trial, so you have to be cautious.”
And Peter Panagos, MD, professor of emergency medicine and neurology at Washington University School of Medicine, St. Louis, said: “It’s great to see this study. The 18% treatment effect is very impressive.”
Dr. Panagos added: “This study addresses a well-described finding from many of the interventional trials, that despite excellent outcomes in recanalization, patients don’t do as well as predicted. The thought is that either re-stenosis or propagation of smaller clots downstream from the original clot in small-caliber vessels [is what] causes additional, unintended damage. The use of intra-arterial thrombolysis after recanalization may assist in dissolving those smaller, downstream clots and debris and improve outcomes.”
But he pointed out that enthusiasm over these results must be matched with some concerns, including the small study size and wide confidence intervals – so larger, randomized studies will be required to confirm and change current clinical practice.
An abbreviated phase 2b trial
The CHOICE trial was conducted in seven centers in Catalonia, Spain.
For the study, patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and who had achieved successful reperfusion (an expanded TICI angiographic score of 2b50 to 3) were randomly assigned to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes or placebo.
Because of the lack of continued availability of placebo supplies, the study had to be stopped early after 121 patients were enrolled (65 alteplase; 56 placebo), and after a few dropouts who did not receive treatment, the analysis was performed on 61 patients who received alteplase and 52 given placebo.
Results showed that the proportion of patients with an mRS score of 0 or 1 at 90 days was 59% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% confidence interval, 0.3%-36.4%; P = .047).
The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, −3.8%; 95% CI, −13.2% to 2.5%).
Mortality at 90 days was 8% with alteplase and 15% with placebo (risk difference, −7.2%; 95% CI, −19.2% to 4.8%).
The improved clinical outcomes in the alteplase group were seen despite only minor differences between the treatment groups in angiographic scores or in other surrogate imaging, Dr. Chamorro pointed out, suggesting that the improved functional outcome may be explained by an amelioration in the microcirculatory reperfusion.
He said the study also supported the safety of intra-arterial alteplase infusion for 15-30 minutes at the dose used. Of note, 60% of the study population had also received IV alteplase before thrombectomy.
In the JAMA study, the authors report that current guidelines recommend that all eligible patients receive intravenous alteplase before thrombectomy, and the results of this trial do not contradict this recommendation.
“The study results support the safety of adjunct intra-arterial alteplase in patients with successful reperfusion at the end of thrombectomy, including in patients treated previously with intravenous alteplase, although the findings on effectiveness should be interpreted as preliminary, requiring replication before any recommendations for practice change,” they concluded.
Dr. Chamorro said that his group was now planning a second larger trial, CHOICE-2.
In an accompanying editorial in JAMA, Pooja Khatri, MD, MSc, University of Cincinnati, said “the 18% treatment effect observed in this 113-patient trial is remarkable.”
However, she cautions that consideration of its clinical implications must be tempered because of the lack of precision of the effect estimate, given wide 95% confidence intervals, the small sample size, and the observation that trials with early termination are well known to overestimate treatment effect.
But she acknowledges that the results suggest “that additional reperfusion therapy may be warranted after relatively successful mechanical thrombectomy of large vessel occlusions, whether to treat the residual primary thrombus, more distal arterial occlusions, or perhaps even microthromboses.”
Dr. Khatri noted that this approach runs counter to the recent movement to consider bypass of intravenous alteplase altogether in thrombectomy-eligible patients and suggests that additional or perhaps more targeted thrombolysis will be the most beneficial approach.
Further studies testing current thrombolytic agents, novel clot-dissolving agents, and other adjunctive antithrombotic and anti-inflammatory agents are needed, she concluded.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Does endovascular therapy benefit strokes with larger ischemic cores?
The RESCUE-JAPAN LIMIT trial was presented at the International Stroke Conference by Shinichi Yoshimura, MD, Hyogo College of Medicine, Nishinomiya, Japan. The study was also published online in the New England Journal of Medicine to coincide with its presentation at the ISC meeting.
The trial showed that among patients with acute stroke and a large ischemic brain region, functional outcomes at 90 days were better with endovascular therapy and medical care than with medical care alone.
Patients who received endovascular therapy were more than twice as likely to have a good functional outcome, defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, than those who received medical care alone.
While the rate of intracranial hemorrhage increased with endovascular therapy, authors of the study and outside commentators suggested that the benefit appeared to outweigh the risk. “Our results provide strong evidence that endovascular therapy improves patient outcomes when the infarct area is large,” Dr. Yoshimura concluded at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Commenting on the study at an ISC press conference, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “The question of strokes with a large core stroke being an exclusion criteria for endovascular therapy is arguably one of the hottest topics the field is facing at this time. There are several randomized trials ongoing aiming to answer this question.”
“The RESCUE-JAPAN trial is the first of these trials to report and shed some light on this issue,” Dr. Jovin added. “The results appear to show that these patients with large core infarcts have just as much benefit from endovascular therapy as patients with smaller infarcts.”
Dr. Jovin described these findings as encouraging but also surprising. “When these large core randomized trials were planned, there was a belief that there would be benefit at some level. But what is surprising to me is that in this trial the benefit was similar to that seen in trials in patients with moderate or small core infarcts. This begs the question of whether we should care about the size of the infarct when we are considering taking these patients for thrombectomy,” he said.
Confirmation needed
On whether this will change practice, Dr. Jovin cautioned that this was just one study with a relatively small number of patients. “I think it is important that all the other randomized trials ongoing should continue so that we have a definitive answer to this question,” he said.
In his presentation, Dr. Yoshimura explained that current guidelines recommended endovascular therapy for patients with large cerebral vessel occlusion and a small or moderate infarct size – an ASPECTS score (Alberta Stroke Program Early Computed Tomographic Score) of 6 or higher. The ASPECTS score has a scale of 1-10, with lower values indicating larger infarction.
The RESCUE-JAPAN LIMIT study included 203 patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an ASPECTS score of 3 to 5.
Patients were randomly assigned to receive endovascular therapy with medical care (endovascular-therapy group) or medical therapy alone (medical-care group) within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images indicating that the infarction was recent.
The percentage of patients with a good outcome as defined by an mRS score of 0 to 3 at 90 days, the primary outcome, was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval, 1.35 to 4.37; P = .002).
Secondary outcomes were mRS scores of 0 to 2 and 0 to 1, an ordinal shift across the range of mRS scores toward a better outcome at 90 days, and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours.
An mRS score of 0 to 2 was seen in 14% of patients in the endovascular-therapy group and 6.9% in the medical-care group (RR, 2.04; 95% CI, 0.86 to 4.84), and an mRS score of 0 to 1 was reported in 5% of the endovascular group versus 2.9% of the medical group (RR, 1.70; 95% CI, 0.42 to 6.93).
The ordinal shift across the range of mRS scores also favored endovascular therapy (common odds ratio, 2.42; 95% CI, 1.46 to 4.01).
An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (RR, 3.51; 95% CI, 1.76 to 7.00).
In terms of safety, any intracranial hemorrhage occurred in 58.0% of patients in the endovascular group and 31.4% of those in the medical therapy group (RR, 1.85; 95% CI, 1.33 to 2.58; P < .001).
There was also a trend toward an increase in symptomatic intracranial hemorrhage in the endovascular group (9% vs. 4.9%), but this did not reach significance (RR, 1.84; 95% CI, 0.64 to 5.29; P = .25).
In the NEJM paper, the authors pointed out that the ASPECTS value in most of the patients in this study was determined with the use of diffusion-weighted MRI, as MRI is widely used in Japan for the diagnosis of acute ischemic stroke. They noted that differences between ASPECTS values based on CT results and those based on diffusion-weighted MRI results should be considered in the interpretation of the results and that previous studies have suggested that an ASPECTS value determined with the use of diffusion-weighted MRI may be one level lower than that determined with the use of CT.
They also noted that there was a relatively low use of thrombolysis in the trial (27% to 29%), which may have altered the outcomes in both groups and disadvantaged the medical-care group. However, they add that most guidelines recommend against the use of thrombolysis when there is extensive ischemic change on imaging.
Risk/benefit trade-off
Commenting on the trade-off between benefits and risks in the study, Dr. Jovin said the increase in intracranial hemorrhage seen in the endovascular group was similar to that seen in other situations.
“This is not really any different from what is seen when giving tPA [tissue plasminogen activator] to stroke patients or when performing thrombectomy in small or moderate core strokes – we know that intracranial hemorrhage is the price to pay,” he stated.
“While the increase in symptomatic intracranial hemorrhage was nonsignificant, the trend is very clear, and I believe it is real,” Dr. Jovin said. “But I think what matters – and what matters to patients – is that there is a much higher chance of having a good outcome with endovascular therapy. I think most patients will accept the extra risk of intracranial hemorrhage if there is an even higher chance of having a better neurological outcome. This is no different to the approach that we take when we treat patients with IV tPA.”
Dr. Jovin pointed out that the RESCUE-JAPAN study did not include the largest core infarcts (ASPECTS score 0-1), but he added that these very large core infarcts are quite rare – especially in patients in the early time window.
He concluded that the study provided important information but cautioned that, with just 200 patients, the findings needed confirmation from other randomized trials that are ongoing.
Also speaking at the ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association, and professor of neurology at Columbia University, New York, said previous trials had established endovascular therapy for patients with large cerebral artery occlusions who have primarily preserved brain tissue and small infarct cores.
“We have picked off the low-lying fruit – the patients with small areas of infarcted brain. But perhaps most patients do not fit into this category and now we are seeing trials addressing these groups,” he said. “This initial study suggests that these patients with larger core infarcts can indeed still benefit from this therapy tremendously.”
The RESCUE-JAPAN LIMIT study was supported in part by the Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy. There was no industry involvement. Dr. Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol-Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, and CSL Behring; and lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer-Ingelheim, Daiichi Sankyo, Bayer, and Bristol-Meyers Squibb.
A version of this article first appeared on Medscape.com.
The RESCUE-JAPAN LIMIT trial was presented at the International Stroke Conference by Shinichi Yoshimura, MD, Hyogo College of Medicine, Nishinomiya, Japan. The study was also published online in the New England Journal of Medicine to coincide with its presentation at the ISC meeting.
The trial showed that among patients with acute stroke and a large ischemic brain region, functional outcomes at 90 days were better with endovascular therapy and medical care than with medical care alone.
Patients who received endovascular therapy were more than twice as likely to have a good functional outcome, defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, than those who received medical care alone.
While the rate of intracranial hemorrhage increased with endovascular therapy, authors of the study and outside commentators suggested that the benefit appeared to outweigh the risk. “Our results provide strong evidence that endovascular therapy improves patient outcomes when the infarct area is large,” Dr. Yoshimura concluded at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Commenting on the study at an ISC press conference, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “The question of strokes with a large core stroke being an exclusion criteria for endovascular therapy is arguably one of the hottest topics the field is facing at this time. There are several randomized trials ongoing aiming to answer this question.”
“The RESCUE-JAPAN trial is the first of these trials to report and shed some light on this issue,” Dr. Jovin added. “The results appear to show that these patients with large core infarcts have just as much benefit from endovascular therapy as patients with smaller infarcts.”
Dr. Jovin described these findings as encouraging but also surprising. “When these large core randomized trials were planned, there was a belief that there would be benefit at some level. But what is surprising to me is that in this trial the benefit was similar to that seen in trials in patients with moderate or small core infarcts. This begs the question of whether we should care about the size of the infarct when we are considering taking these patients for thrombectomy,” he said.
Confirmation needed
On whether this will change practice, Dr. Jovin cautioned that this was just one study with a relatively small number of patients. “I think it is important that all the other randomized trials ongoing should continue so that we have a definitive answer to this question,” he said.
In his presentation, Dr. Yoshimura explained that current guidelines recommended endovascular therapy for patients with large cerebral vessel occlusion and a small or moderate infarct size – an ASPECTS score (Alberta Stroke Program Early Computed Tomographic Score) of 6 or higher. The ASPECTS score has a scale of 1-10, with lower values indicating larger infarction.
The RESCUE-JAPAN LIMIT study included 203 patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an ASPECTS score of 3 to 5.
Patients were randomly assigned to receive endovascular therapy with medical care (endovascular-therapy group) or medical therapy alone (medical-care group) within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images indicating that the infarction was recent.
The percentage of patients with a good outcome as defined by an mRS score of 0 to 3 at 90 days, the primary outcome, was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval, 1.35 to 4.37; P = .002).
Secondary outcomes were mRS scores of 0 to 2 and 0 to 1, an ordinal shift across the range of mRS scores toward a better outcome at 90 days, and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours.
An mRS score of 0 to 2 was seen in 14% of patients in the endovascular-therapy group and 6.9% in the medical-care group (RR, 2.04; 95% CI, 0.86 to 4.84), and an mRS score of 0 to 1 was reported in 5% of the endovascular group versus 2.9% of the medical group (RR, 1.70; 95% CI, 0.42 to 6.93).
The ordinal shift across the range of mRS scores also favored endovascular therapy (common odds ratio, 2.42; 95% CI, 1.46 to 4.01).
An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (RR, 3.51; 95% CI, 1.76 to 7.00).
In terms of safety, any intracranial hemorrhage occurred in 58.0% of patients in the endovascular group and 31.4% of those in the medical therapy group (RR, 1.85; 95% CI, 1.33 to 2.58; P < .001).
There was also a trend toward an increase in symptomatic intracranial hemorrhage in the endovascular group (9% vs. 4.9%), but this did not reach significance (RR, 1.84; 95% CI, 0.64 to 5.29; P = .25).
In the NEJM paper, the authors pointed out that the ASPECTS value in most of the patients in this study was determined with the use of diffusion-weighted MRI, as MRI is widely used in Japan for the diagnosis of acute ischemic stroke. They noted that differences between ASPECTS values based on CT results and those based on diffusion-weighted MRI results should be considered in the interpretation of the results and that previous studies have suggested that an ASPECTS value determined with the use of diffusion-weighted MRI may be one level lower than that determined with the use of CT.
They also noted that there was a relatively low use of thrombolysis in the trial (27% to 29%), which may have altered the outcomes in both groups and disadvantaged the medical-care group. However, they add that most guidelines recommend against the use of thrombolysis when there is extensive ischemic change on imaging.
Risk/benefit trade-off
Commenting on the trade-off between benefits and risks in the study, Dr. Jovin said the increase in intracranial hemorrhage seen in the endovascular group was similar to that seen in other situations.
“This is not really any different from what is seen when giving tPA [tissue plasminogen activator] to stroke patients or when performing thrombectomy in small or moderate core strokes – we know that intracranial hemorrhage is the price to pay,” he stated.
“While the increase in symptomatic intracranial hemorrhage was nonsignificant, the trend is very clear, and I believe it is real,” Dr. Jovin said. “But I think what matters – and what matters to patients – is that there is a much higher chance of having a good outcome with endovascular therapy. I think most patients will accept the extra risk of intracranial hemorrhage if there is an even higher chance of having a better neurological outcome. This is no different to the approach that we take when we treat patients with IV tPA.”
Dr. Jovin pointed out that the RESCUE-JAPAN study did not include the largest core infarcts (ASPECTS score 0-1), but he added that these very large core infarcts are quite rare – especially in patients in the early time window.
He concluded that the study provided important information but cautioned that, with just 200 patients, the findings needed confirmation from other randomized trials that are ongoing.
Also speaking at the ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association, and professor of neurology at Columbia University, New York, said previous trials had established endovascular therapy for patients with large cerebral artery occlusions who have primarily preserved brain tissue and small infarct cores.
“We have picked off the low-lying fruit – the patients with small areas of infarcted brain. But perhaps most patients do not fit into this category and now we are seeing trials addressing these groups,” he said. “This initial study suggests that these patients with larger core infarcts can indeed still benefit from this therapy tremendously.”
The RESCUE-JAPAN LIMIT study was supported in part by the Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy. There was no industry involvement. Dr. Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol-Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, and CSL Behring; and lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer-Ingelheim, Daiichi Sankyo, Bayer, and Bristol-Meyers Squibb.
A version of this article first appeared on Medscape.com.
The RESCUE-JAPAN LIMIT trial was presented at the International Stroke Conference by Shinichi Yoshimura, MD, Hyogo College of Medicine, Nishinomiya, Japan. The study was also published online in the New England Journal of Medicine to coincide with its presentation at the ISC meeting.
The trial showed that among patients with acute stroke and a large ischemic brain region, functional outcomes at 90 days were better with endovascular therapy and medical care than with medical care alone.
Patients who received endovascular therapy were more than twice as likely to have a good functional outcome, defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, than those who received medical care alone.
While the rate of intracranial hemorrhage increased with endovascular therapy, authors of the study and outside commentators suggested that the benefit appeared to outweigh the risk. “Our results provide strong evidence that endovascular therapy improves patient outcomes when the infarct area is large,” Dr. Yoshimura concluded at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Commenting on the study at an ISC press conference, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “The question of strokes with a large core stroke being an exclusion criteria for endovascular therapy is arguably one of the hottest topics the field is facing at this time. There are several randomized trials ongoing aiming to answer this question.”
“The RESCUE-JAPAN trial is the first of these trials to report and shed some light on this issue,” Dr. Jovin added. “The results appear to show that these patients with large core infarcts have just as much benefit from endovascular therapy as patients with smaller infarcts.”
Dr. Jovin described these findings as encouraging but also surprising. “When these large core randomized trials were planned, there was a belief that there would be benefit at some level. But what is surprising to me is that in this trial the benefit was similar to that seen in trials in patients with moderate or small core infarcts. This begs the question of whether we should care about the size of the infarct when we are considering taking these patients for thrombectomy,” he said.
Confirmation needed
On whether this will change practice, Dr. Jovin cautioned that this was just one study with a relatively small number of patients. “I think it is important that all the other randomized trials ongoing should continue so that we have a definitive answer to this question,” he said.
In his presentation, Dr. Yoshimura explained that current guidelines recommended endovascular therapy for patients with large cerebral vessel occlusion and a small or moderate infarct size – an ASPECTS score (Alberta Stroke Program Early Computed Tomographic Score) of 6 or higher. The ASPECTS score has a scale of 1-10, with lower values indicating larger infarction.
The RESCUE-JAPAN LIMIT study included 203 patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an ASPECTS score of 3 to 5.
Patients were randomly assigned to receive endovascular therapy with medical care (endovascular-therapy group) or medical therapy alone (medical-care group) within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images indicating that the infarction was recent.
The percentage of patients with a good outcome as defined by an mRS score of 0 to 3 at 90 days, the primary outcome, was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval, 1.35 to 4.37; P = .002).
Secondary outcomes were mRS scores of 0 to 2 and 0 to 1, an ordinal shift across the range of mRS scores toward a better outcome at 90 days, and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours.
An mRS score of 0 to 2 was seen in 14% of patients in the endovascular-therapy group and 6.9% in the medical-care group (RR, 2.04; 95% CI, 0.86 to 4.84), and an mRS score of 0 to 1 was reported in 5% of the endovascular group versus 2.9% of the medical group (RR, 1.70; 95% CI, 0.42 to 6.93).
The ordinal shift across the range of mRS scores also favored endovascular therapy (common odds ratio, 2.42; 95% CI, 1.46 to 4.01).
An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (RR, 3.51; 95% CI, 1.76 to 7.00).
In terms of safety, any intracranial hemorrhage occurred in 58.0% of patients in the endovascular group and 31.4% of those in the medical therapy group (RR, 1.85; 95% CI, 1.33 to 2.58; P < .001).
There was also a trend toward an increase in symptomatic intracranial hemorrhage in the endovascular group (9% vs. 4.9%), but this did not reach significance (RR, 1.84; 95% CI, 0.64 to 5.29; P = .25).
In the NEJM paper, the authors pointed out that the ASPECTS value in most of the patients in this study was determined with the use of diffusion-weighted MRI, as MRI is widely used in Japan for the diagnosis of acute ischemic stroke. They noted that differences between ASPECTS values based on CT results and those based on diffusion-weighted MRI results should be considered in the interpretation of the results and that previous studies have suggested that an ASPECTS value determined with the use of diffusion-weighted MRI may be one level lower than that determined with the use of CT.
They also noted that there was a relatively low use of thrombolysis in the trial (27% to 29%), which may have altered the outcomes in both groups and disadvantaged the medical-care group. However, they add that most guidelines recommend against the use of thrombolysis when there is extensive ischemic change on imaging.
Risk/benefit trade-off
Commenting on the trade-off between benefits and risks in the study, Dr. Jovin said the increase in intracranial hemorrhage seen in the endovascular group was similar to that seen in other situations.
“This is not really any different from what is seen when giving tPA [tissue plasminogen activator] to stroke patients or when performing thrombectomy in small or moderate core strokes – we know that intracranial hemorrhage is the price to pay,” he stated.
“While the increase in symptomatic intracranial hemorrhage was nonsignificant, the trend is very clear, and I believe it is real,” Dr. Jovin said. “But I think what matters – and what matters to patients – is that there is a much higher chance of having a good outcome with endovascular therapy. I think most patients will accept the extra risk of intracranial hemorrhage if there is an even higher chance of having a better neurological outcome. This is no different to the approach that we take when we treat patients with IV tPA.”
Dr. Jovin pointed out that the RESCUE-JAPAN study did not include the largest core infarcts (ASPECTS score 0-1), but he added that these very large core infarcts are quite rare – especially in patients in the early time window.
He concluded that the study provided important information but cautioned that, with just 200 patients, the findings needed confirmation from other randomized trials that are ongoing.
Also speaking at the ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association, and professor of neurology at Columbia University, New York, said previous trials had established endovascular therapy for patients with large cerebral artery occlusions who have primarily preserved brain tissue and small infarct cores.
“We have picked off the low-lying fruit – the patients with small areas of infarcted brain. But perhaps most patients do not fit into this category and now we are seeing trials addressing these groups,” he said. “This initial study suggests that these patients with larger core infarcts can indeed still benefit from this therapy tremendously.”
The RESCUE-JAPAN LIMIT study was supported in part by the Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy. There was no industry involvement. Dr. Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol-Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, and CSL Behring; and lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer-Ingelheim, Daiichi Sankyo, Bayer, and Bristol-Meyers Squibb.
A version of this article first appeared on Medscape.com.
FROM ISC 2022
Ischemic stroke rates higher in young women than young men
Young women appear to be at a higher risk of ischemic stroke than young men, according to a new systematic review of studies on this topic.
The review included 19 studies that reported on sex-specific stroke incidence among young adults and found that overall, in young adults aged 18-35 years, there were 44% more women with ischemic strokes than men.
This gap narrowed in the age group 35-45 years, for which there was conflicting evidence whether more men or women have ischemic strokes.
“An assertion that young women may be disproportionately at risk of ischemic stroke represents a significant departure from our current scientific understanding and may have important implications about the etiology of ischemic strokes in young adults,” the authors note.
“One of the take-home messages from this study is that stroke happens across the entire age spectrum, including young adults, even if they do not have traditional risk factors,” study coauthor Sharon N. Poisson, MD, associate professor of neurology at the University of Colorado Anschutz Medical Campus, Denver, told this news organization.
“If a young person presents with focal neurological symptoms, the possibility of a stroke should not be discounted just because they may not fit the typical profile of a stroke patient. We need more education of the population that young people – including young women – can have a stroke and that fast action to call emergency services is critical,” she said.
The study was published online Jan. 24 in the journal Stroke as part of a special “Go Red for Women” spotlight issue.
The researchers note that historically it has been believed that men have a higher incidence of stroke in every age group until very old age. However, recent evidence focused on the young adult age group has reported that there are more young women (ages 18-45) with ischemic strokes compared with young men, suggesting that young women may be disproportionately at risk compared with their male counterparts.
Pointing out that a better understanding of these sex differences is important in implementing strategies that can more effectively prevent and treat strokes in this age group, the researchers conducted the current review to synthesize the updated evidence.
They searched PubMed from January 2008 to July 2021 for relevant studies that were population-based and reported stroke incidence by sex or sex-specific incidence rate ratios of young adults age 45 and younger. Statistical synthesis was performed to estimate sex difference by age group (less than or equal to 35, 35-45 and less than or equal to 45 years) and stroke type.
They found 19 relevant studies, including three that reported on overlapping data, with a total of 69,793 young adults (33,775 women and 36,018 men).
Nine studies did not show a statistically significant sex difference among young adults less than or equal to 45 years. Three studies found higher rates of ischemic stroke among men among young adults less than or equal to 30 to 35 years. Four studies showed more women with ischemic strokes among young adults less than or equal to 35 years.
Overall, there was an effect of a significantly higher incidence of ischemic stroke in women younger than age 35 years, with an incidence rate ratio (IRR) of 1.44. In the 35- to 45-year age group, there was a nonsignificant sex difference in the rate of ischemic stroke, with a slight trend toward a higher incidence in women (IRR, 1.08).
“In this study the sex difference was not clear in the 35-45 age group. But in the age group of over 45 years we know that men have a higher risk of stroke than women, which is probably related to a higher level of atherosclerotic risk factors,” Dr. Poisson commented.
“Interpreting data on stroke in young people is challenging, as stroke is not so common in this population,” she said. “Combining multiple studies helps, but this also introduces a lot of variability, so we need to interpret these results with some caution. However, this is certainly intriguing data and suggests that something interesting may be going on in young adults,” she added. “These observations give us an initial clue that we need to look further into this issue.”
The study did not look at the possible mechanisms behind the results, as the current data came from administrative datasets that are limited in terms of the information collected.
But Dr. Poisson noted that the traditional risk factors for stroke are high blood pressure and the usual atherosclerotic factors such as high cholesterol.
“These are normally more common in men than in women, and myocardial infarction is more common in younger men than in younger women. But the observation that young women may have a higher risk of stroke than young men suggests that something different may be going on in the mechanism for stroke.”
She pointed out that women have some unique risk factors for stroke, including oral contraceptive use, pregnancy, and the postpartum period, particularly pre-eclampsia during pregnancy. In addition, migraine, especially migraine with aura, is associated with an increased stroke risk, and migraine is more common in young women than in young men.
“We don’t completely understand the role of these risk factors, but they may contribute to the results that we found,” Dr. Poisson commented. “The role of estrogen in stroke is complicated. While estrogen is generally thought to be protective against atherosclerotic risk factors, it also increases risk of clotting, so high estrogen states like pregnancy increase risk of stroke,” she added.
To better understand what is happening, prospectively collected clinical data on younger patients who have had a stroke are needed. Some such studies are underway, but a concerted effort to do this in a large, multicenter registry would be desirable, Dr. Poisson said.
She noted that the presentation of a stroke in young people would be similar to that in the older population, with the most recent acronym to help recognize stroke symptoms being “BE FAST” – balance, eyes (vision), face (drooping), arm, speech (slurred), time (call emergency services quickly).
Call for more women in clinical trials
In an accompanying commentary, Cheryl Bushnell, MD, professor of neurology at Wake Forest School of Medicine, Winston-Salem, N.C., and Moira Kapral, MD, professor in medicine and health policy at the University of Toronto, say these findings support the need for further study to understand and address the causes and risk factors of stroke in young women.
However, they point out that representation and reporting of women in clinical trials of acute stroke continues to be suboptimal, and they call for improved incorporation of sex and gender into study design, analysis, and interpretation, which they say is critical for producing research that is broadly generalizable and applicable to different populations.
Coauthor Stacey L. Daugherty, MD, is funded by the National Institutes of Health. Dr. Poisson and Dr. Kapral have disclosed no relevant financial relationships. Dr. Bushnell reports ownership interest in Care Directions.
A version of this article first appeared on Medscape.com.
Young women appear to be at a higher risk of ischemic stroke than young men, according to a new systematic review of studies on this topic.
The review included 19 studies that reported on sex-specific stroke incidence among young adults and found that overall, in young adults aged 18-35 years, there were 44% more women with ischemic strokes than men.
This gap narrowed in the age group 35-45 years, for which there was conflicting evidence whether more men or women have ischemic strokes.
“An assertion that young women may be disproportionately at risk of ischemic stroke represents a significant departure from our current scientific understanding and may have important implications about the etiology of ischemic strokes in young adults,” the authors note.
“One of the take-home messages from this study is that stroke happens across the entire age spectrum, including young adults, even if they do not have traditional risk factors,” study coauthor Sharon N. Poisson, MD, associate professor of neurology at the University of Colorado Anschutz Medical Campus, Denver, told this news organization.
“If a young person presents with focal neurological symptoms, the possibility of a stroke should not be discounted just because they may not fit the typical profile of a stroke patient. We need more education of the population that young people – including young women – can have a stroke and that fast action to call emergency services is critical,” she said.
The study was published online Jan. 24 in the journal Stroke as part of a special “Go Red for Women” spotlight issue.
The researchers note that historically it has been believed that men have a higher incidence of stroke in every age group until very old age. However, recent evidence focused on the young adult age group has reported that there are more young women (ages 18-45) with ischemic strokes compared with young men, suggesting that young women may be disproportionately at risk compared with their male counterparts.
Pointing out that a better understanding of these sex differences is important in implementing strategies that can more effectively prevent and treat strokes in this age group, the researchers conducted the current review to synthesize the updated evidence.
They searched PubMed from January 2008 to July 2021 for relevant studies that were population-based and reported stroke incidence by sex or sex-specific incidence rate ratios of young adults age 45 and younger. Statistical synthesis was performed to estimate sex difference by age group (less than or equal to 35, 35-45 and less than or equal to 45 years) and stroke type.
They found 19 relevant studies, including three that reported on overlapping data, with a total of 69,793 young adults (33,775 women and 36,018 men).
Nine studies did not show a statistically significant sex difference among young adults less than or equal to 45 years. Three studies found higher rates of ischemic stroke among men among young adults less than or equal to 30 to 35 years. Four studies showed more women with ischemic strokes among young adults less than or equal to 35 years.
Overall, there was an effect of a significantly higher incidence of ischemic stroke in women younger than age 35 years, with an incidence rate ratio (IRR) of 1.44. In the 35- to 45-year age group, there was a nonsignificant sex difference in the rate of ischemic stroke, with a slight trend toward a higher incidence in women (IRR, 1.08).
“In this study the sex difference was not clear in the 35-45 age group. But in the age group of over 45 years we know that men have a higher risk of stroke than women, which is probably related to a higher level of atherosclerotic risk factors,” Dr. Poisson commented.
“Interpreting data on stroke in young people is challenging, as stroke is not so common in this population,” she said. “Combining multiple studies helps, but this also introduces a lot of variability, so we need to interpret these results with some caution. However, this is certainly intriguing data and suggests that something interesting may be going on in young adults,” she added. “These observations give us an initial clue that we need to look further into this issue.”
The study did not look at the possible mechanisms behind the results, as the current data came from administrative datasets that are limited in terms of the information collected.
But Dr. Poisson noted that the traditional risk factors for stroke are high blood pressure and the usual atherosclerotic factors such as high cholesterol.
“These are normally more common in men than in women, and myocardial infarction is more common in younger men than in younger women. But the observation that young women may have a higher risk of stroke than young men suggests that something different may be going on in the mechanism for stroke.”
She pointed out that women have some unique risk factors for stroke, including oral contraceptive use, pregnancy, and the postpartum period, particularly pre-eclampsia during pregnancy. In addition, migraine, especially migraine with aura, is associated with an increased stroke risk, and migraine is more common in young women than in young men.
“We don’t completely understand the role of these risk factors, but they may contribute to the results that we found,” Dr. Poisson commented. “The role of estrogen in stroke is complicated. While estrogen is generally thought to be protective against atherosclerotic risk factors, it also increases risk of clotting, so high estrogen states like pregnancy increase risk of stroke,” she added.
To better understand what is happening, prospectively collected clinical data on younger patients who have had a stroke are needed. Some such studies are underway, but a concerted effort to do this in a large, multicenter registry would be desirable, Dr. Poisson said.
She noted that the presentation of a stroke in young people would be similar to that in the older population, with the most recent acronym to help recognize stroke symptoms being “BE FAST” – balance, eyes (vision), face (drooping), arm, speech (slurred), time (call emergency services quickly).
Call for more women in clinical trials
In an accompanying commentary, Cheryl Bushnell, MD, professor of neurology at Wake Forest School of Medicine, Winston-Salem, N.C., and Moira Kapral, MD, professor in medicine and health policy at the University of Toronto, say these findings support the need for further study to understand and address the causes and risk factors of stroke in young women.
However, they point out that representation and reporting of women in clinical trials of acute stroke continues to be suboptimal, and they call for improved incorporation of sex and gender into study design, analysis, and interpretation, which they say is critical for producing research that is broadly generalizable and applicable to different populations.
Coauthor Stacey L. Daugherty, MD, is funded by the National Institutes of Health. Dr. Poisson and Dr. Kapral have disclosed no relevant financial relationships. Dr. Bushnell reports ownership interest in Care Directions.
A version of this article first appeared on Medscape.com.
Young women appear to be at a higher risk of ischemic stroke than young men, according to a new systematic review of studies on this topic.
The review included 19 studies that reported on sex-specific stroke incidence among young adults and found that overall, in young adults aged 18-35 years, there were 44% more women with ischemic strokes than men.
This gap narrowed in the age group 35-45 years, for which there was conflicting evidence whether more men or women have ischemic strokes.
“An assertion that young women may be disproportionately at risk of ischemic stroke represents a significant departure from our current scientific understanding and may have important implications about the etiology of ischemic strokes in young adults,” the authors note.
“One of the take-home messages from this study is that stroke happens across the entire age spectrum, including young adults, even if they do not have traditional risk factors,” study coauthor Sharon N. Poisson, MD, associate professor of neurology at the University of Colorado Anschutz Medical Campus, Denver, told this news organization.
“If a young person presents with focal neurological symptoms, the possibility of a stroke should not be discounted just because they may not fit the typical profile of a stroke patient. We need more education of the population that young people – including young women – can have a stroke and that fast action to call emergency services is critical,” she said.
The study was published online Jan. 24 in the journal Stroke as part of a special “Go Red for Women” spotlight issue.
The researchers note that historically it has been believed that men have a higher incidence of stroke in every age group until very old age. However, recent evidence focused on the young adult age group has reported that there are more young women (ages 18-45) with ischemic strokes compared with young men, suggesting that young women may be disproportionately at risk compared with their male counterparts.
Pointing out that a better understanding of these sex differences is important in implementing strategies that can more effectively prevent and treat strokes in this age group, the researchers conducted the current review to synthesize the updated evidence.
They searched PubMed from January 2008 to July 2021 for relevant studies that were population-based and reported stroke incidence by sex or sex-specific incidence rate ratios of young adults age 45 and younger. Statistical synthesis was performed to estimate sex difference by age group (less than or equal to 35, 35-45 and less than or equal to 45 years) and stroke type.
They found 19 relevant studies, including three that reported on overlapping data, with a total of 69,793 young adults (33,775 women and 36,018 men).
Nine studies did not show a statistically significant sex difference among young adults less than or equal to 45 years. Three studies found higher rates of ischemic stroke among men among young adults less than or equal to 30 to 35 years. Four studies showed more women with ischemic strokes among young adults less than or equal to 35 years.
Overall, there was an effect of a significantly higher incidence of ischemic stroke in women younger than age 35 years, with an incidence rate ratio (IRR) of 1.44. In the 35- to 45-year age group, there was a nonsignificant sex difference in the rate of ischemic stroke, with a slight trend toward a higher incidence in women (IRR, 1.08).
“In this study the sex difference was not clear in the 35-45 age group. But in the age group of over 45 years we know that men have a higher risk of stroke than women, which is probably related to a higher level of atherosclerotic risk factors,” Dr. Poisson commented.
“Interpreting data on stroke in young people is challenging, as stroke is not so common in this population,” she said. “Combining multiple studies helps, but this also introduces a lot of variability, so we need to interpret these results with some caution. However, this is certainly intriguing data and suggests that something interesting may be going on in young adults,” she added. “These observations give us an initial clue that we need to look further into this issue.”
The study did not look at the possible mechanisms behind the results, as the current data came from administrative datasets that are limited in terms of the information collected.
But Dr. Poisson noted that the traditional risk factors for stroke are high blood pressure and the usual atherosclerotic factors such as high cholesterol.
“These are normally more common in men than in women, and myocardial infarction is more common in younger men than in younger women. But the observation that young women may have a higher risk of stroke than young men suggests that something different may be going on in the mechanism for stroke.”
She pointed out that women have some unique risk factors for stroke, including oral contraceptive use, pregnancy, and the postpartum period, particularly pre-eclampsia during pregnancy. In addition, migraine, especially migraine with aura, is associated with an increased stroke risk, and migraine is more common in young women than in young men.
“We don’t completely understand the role of these risk factors, but they may contribute to the results that we found,” Dr. Poisson commented. “The role of estrogen in stroke is complicated. While estrogen is generally thought to be protective against atherosclerotic risk factors, it also increases risk of clotting, so high estrogen states like pregnancy increase risk of stroke,” she added.
To better understand what is happening, prospectively collected clinical data on younger patients who have had a stroke are needed. Some such studies are underway, but a concerted effort to do this in a large, multicenter registry would be desirable, Dr. Poisson said.
She noted that the presentation of a stroke in young people would be similar to that in the older population, with the most recent acronym to help recognize stroke symptoms being “BE FAST” – balance, eyes (vision), face (drooping), arm, speech (slurred), time (call emergency services quickly).
Call for more women in clinical trials
In an accompanying commentary, Cheryl Bushnell, MD, professor of neurology at Wake Forest School of Medicine, Winston-Salem, N.C., and Moira Kapral, MD, professor in medicine and health policy at the University of Toronto, say these findings support the need for further study to understand and address the causes and risk factors of stroke in young women.
However, they point out that representation and reporting of women in clinical trials of acute stroke continues to be suboptimal, and they call for improved incorporation of sex and gender into study design, analysis, and interpretation, which they say is critical for producing research that is broadly generalizable and applicable to different populations.
Coauthor Stacey L. Daugherty, MD, is funded by the National Institutes of Health. Dr. Poisson and Dr. Kapral have disclosed no relevant financial relationships. Dr. Bushnell reports ownership interest in Care Directions.
A version of this article first appeared on Medscape.com.
Yoga maneuver may prevent vasovagal syncope
The tadasana exercise – a movement-based contemplative practice that gradually corrects orthostatic imbalance by strengthening protective neuromuscular reflexes – practiced for just 15 minutes twice a day, was associated with the complete elimination of episodes of vasovagal syncope for many patients.
“These exercises are very easy to perform, inexpensive, and very effective. This is a very easy fix for a scary and potentially dangerous condition,” lead author Hygriv Rao, MD, said in an interview. “We are excited about these results. We thought it would work, but we did not expect it to be so effective. It seems to work for almost all patients.
“We found that, with the tadasana maneuver, episodes of full syncope, where the patient actually loses consciousness, ceased completely, and episodes of near-syncope, where the patient feels faint but does not completely pass out, were greatly reduced,” Dr. Rao added. “The actual loss of consciousness, which is the most dangerous part, is practically gone. This gives a lot of confidence to patients and their families.”
The researchers reported their initial results from a pilot study of the technique in a letter to JACC: Clinical Electrophysiology that was published online Jan. 26, 2022.
Dr. Rao, a cardiologist at the KIMS Hospitals, Hyderabad, India, explained that vasovagal syncope is a brief loss of consciousness caused by a neurologically induced drop in blood pressure caused by faulty neuromuscular reflexes.
It is typically triggered by emotional stress, prolonged standing, or getting up from a sitting position too quickly.
Very few treatments have been shown effective, with current management approaches involving avoiding triggers, increasing fluids, and if the individual feels an episode coming on, they can take steps to stop it by lying down, raising their legs, or lowering their head to increase blood flow to the brain.
“Recently, there has been a lot of interest in yoga as a preventative therapy for vasovagal syncope,” Dr. Rao noted. “We considered various yoga positions and we chose the tadasana maneuver to study in this context as it resembles exercises sometimes given to patients with vasovagal syncope but with some differences including the addition of synchronized breathing, which may help stabilize autonomic tone.”
For the tadasana maneuver, the individual stands straight with their feet together, arms by their side (against a wall if they need support), and alternatively lift the front and back part of their feet.
They first lift their toes with their weight resting on the ball of their feet, then after a few seconds they raise their heels with their weight on the front of the foot. Then after a few more seconds they lift their arms over their shoulders, stretching upward while standing on their toes.
These movements are synchronized with breathing exercises, with the individual taking a deep breath in as they lift their arms and breathing out again on lowering the arms.
“Each movement takes a few seconds, and each cycle of movements takes about 2 minutes. If this is performed 8 times, then this would take about 15 minutes. We recommend this 15-minute routine twice a day,” Dr. Rao said.
For the current study, 113 patients diagnosed with recurrent vasovagal disorder were counseled to practice standard physical maneuvers and maintain adequate hydration. Medications were prescribed at the discretion of the treating physician.
Of these, 61 patients were additionally trained to practice the tadasana maneuver and asked to practice the movement for 15 minutes twice a day. The mean durations of symptoms and follow-up in the two groups were similar. The average follow-up was about 20 months.
Results showed that episodes of both near-syncope and syncope decreased in both groups but there was a much larger reduction in the patients practicing the tadasana maneuver.
Before treatment, the 52 patients in the conventional group experienced 163 syncope or near-syncope events. At follow-up, 22 symptom recurrences occurred in 12 patients (23%). Total mean events per patient declined from 3 to 0.4.
Full syncope events in this group declined from 65 in 32 patients to 2 in 2 patients (mean per patient, 1.3 to 1), and near-syncope events fell from 98 in 34 patients to 20 in 10 patients (mean per patient, 2.0 to 0.4).
In the tadasana group, 61 patients had 378 syncope/near-syncope events before treatment; at follow-up, only 6 events occurred in 5 patients (8%). Per patient, total events declined from a mean of 6 to 0.1.
Full syncope events fell from 108 in 48 patients to 0 (mean per patient, 1.8 to 0), and near-syncope events declined from 269 in 33 patients to 6 in 5 patients (mean per patient, 4.4 to 0.1).
“This combination of exercise and breathing influences the neuromuscular reflex malfunction that occurs in vasovagal syncope,” Dr. Rao noted. “The movements focus on strengthening neuromuscular reflexes in the quadriceps and the calf muscles, which can increase the blood circulation and venous return, thus preventing blood pooling in the lower body.”
The researchers said this pilot study offers three main findings. First, both conventional therapy and conventional plus tadasana therapy appeared to benefit patients, compared with their respective baseline symptom burden. Second, application of tadasana as an adjunctive treatment was associated with fewer total event recurrences (that is, syncope and near-syncope combined), and third, tadasana was well tolerated, with no adverse events reported.
“The reduction in total events (i.e., syncope and near-syncope events), compared with pretreatment numbers, was substantial and most tadasana patients were managed without any pharmacotherapy,” the authors reported.
Dr. Rao noted that at baseline almost all patients in both groups were taking medications for the condition, but during the study these medications were reduced as fewer episodes occurred. At the end of the follow-up, 80% of the conventional group were still taking medication, compared with just 14% of those in the tadasana group.
Patients had an initial training session in person with a yoga instructor and then received follow-on training by video online. Dr. Rao said there was a very high rate of compliance, “almost 100%.”
He reports that a total of 200 patients have now been treated with this approach at his hospital with very similar results to those seen in the initial study.
This work was supported in part by a grant from the Dr Earl E. Bakken Family in support of heart-brain research. Dr. Rao disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The tadasana exercise – a movement-based contemplative practice that gradually corrects orthostatic imbalance by strengthening protective neuromuscular reflexes – practiced for just 15 minutes twice a day, was associated with the complete elimination of episodes of vasovagal syncope for many patients.
“These exercises are very easy to perform, inexpensive, and very effective. This is a very easy fix for a scary and potentially dangerous condition,” lead author Hygriv Rao, MD, said in an interview. “We are excited about these results. We thought it would work, but we did not expect it to be so effective. It seems to work for almost all patients.
“We found that, with the tadasana maneuver, episodes of full syncope, where the patient actually loses consciousness, ceased completely, and episodes of near-syncope, where the patient feels faint but does not completely pass out, were greatly reduced,” Dr. Rao added. “The actual loss of consciousness, which is the most dangerous part, is practically gone. This gives a lot of confidence to patients and their families.”
The researchers reported their initial results from a pilot study of the technique in a letter to JACC: Clinical Electrophysiology that was published online Jan. 26, 2022.
Dr. Rao, a cardiologist at the KIMS Hospitals, Hyderabad, India, explained that vasovagal syncope is a brief loss of consciousness caused by a neurologically induced drop in blood pressure caused by faulty neuromuscular reflexes.
It is typically triggered by emotional stress, prolonged standing, or getting up from a sitting position too quickly.
Very few treatments have been shown effective, with current management approaches involving avoiding triggers, increasing fluids, and if the individual feels an episode coming on, they can take steps to stop it by lying down, raising their legs, or lowering their head to increase blood flow to the brain.
“Recently, there has been a lot of interest in yoga as a preventative therapy for vasovagal syncope,” Dr. Rao noted. “We considered various yoga positions and we chose the tadasana maneuver to study in this context as it resembles exercises sometimes given to patients with vasovagal syncope but with some differences including the addition of synchronized breathing, which may help stabilize autonomic tone.”
For the tadasana maneuver, the individual stands straight with their feet together, arms by their side (against a wall if they need support), and alternatively lift the front and back part of their feet.
They first lift their toes with their weight resting on the ball of their feet, then after a few seconds they raise their heels with their weight on the front of the foot. Then after a few more seconds they lift their arms over their shoulders, stretching upward while standing on their toes.
These movements are synchronized with breathing exercises, with the individual taking a deep breath in as they lift their arms and breathing out again on lowering the arms.
“Each movement takes a few seconds, and each cycle of movements takes about 2 minutes. If this is performed 8 times, then this would take about 15 minutes. We recommend this 15-minute routine twice a day,” Dr. Rao said.
For the current study, 113 patients diagnosed with recurrent vasovagal disorder were counseled to practice standard physical maneuvers and maintain adequate hydration. Medications were prescribed at the discretion of the treating physician.
Of these, 61 patients were additionally trained to practice the tadasana maneuver and asked to practice the movement for 15 minutes twice a day. The mean durations of symptoms and follow-up in the two groups were similar. The average follow-up was about 20 months.
Results showed that episodes of both near-syncope and syncope decreased in both groups but there was a much larger reduction in the patients practicing the tadasana maneuver.
Before treatment, the 52 patients in the conventional group experienced 163 syncope or near-syncope events. At follow-up, 22 symptom recurrences occurred in 12 patients (23%). Total mean events per patient declined from 3 to 0.4.
Full syncope events in this group declined from 65 in 32 patients to 2 in 2 patients (mean per patient, 1.3 to 1), and near-syncope events fell from 98 in 34 patients to 20 in 10 patients (mean per patient, 2.0 to 0.4).
In the tadasana group, 61 patients had 378 syncope/near-syncope events before treatment; at follow-up, only 6 events occurred in 5 patients (8%). Per patient, total events declined from a mean of 6 to 0.1.
Full syncope events fell from 108 in 48 patients to 0 (mean per patient, 1.8 to 0), and near-syncope events declined from 269 in 33 patients to 6 in 5 patients (mean per patient, 4.4 to 0.1).
“This combination of exercise and breathing influences the neuromuscular reflex malfunction that occurs in vasovagal syncope,” Dr. Rao noted. “The movements focus on strengthening neuromuscular reflexes in the quadriceps and the calf muscles, which can increase the blood circulation and venous return, thus preventing blood pooling in the lower body.”
The researchers said this pilot study offers three main findings. First, both conventional therapy and conventional plus tadasana therapy appeared to benefit patients, compared with their respective baseline symptom burden. Second, application of tadasana as an adjunctive treatment was associated with fewer total event recurrences (that is, syncope and near-syncope combined), and third, tadasana was well tolerated, with no adverse events reported.
“The reduction in total events (i.e., syncope and near-syncope events), compared with pretreatment numbers, was substantial and most tadasana patients were managed without any pharmacotherapy,” the authors reported.
Dr. Rao noted that at baseline almost all patients in both groups were taking medications for the condition, but during the study these medications were reduced as fewer episodes occurred. At the end of the follow-up, 80% of the conventional group were still taking medication, compared with just 14% of those in the tadasana group.
Patients had an initial training session in person with a yoga instructor and then received follow-on training by video online. Dr. Rao said there was a very high rate of compliance, “almost 100%.”
He reports that a total of 200 patients have now been treated with this approach at his hospital with very similar results to those seen in the initial study.
This work was supported in part by a grant from the Dr Earl E. Bakken Family in support of heart-brain research. Dr. Rao disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The tadasana exercise – a movement-based contemplative practice that gradually corrects orthostatic imbalance by strengthening protective neuromuscular reflexes – practiced for just 15 minutes twice a day, was associated with the complete elimination of episodes of vasovagal syncope for many patients.
“These exercises are very easy to perform, inexpensive, and very effective. This is a very easy fix for a scary and potentially dangerous condition,” lead author Hygriv Rao, MD, said in an interview. “We are excited about these results. We thought it would work, but we did not expect it to be so effective. It seems to work for almost all patients.
“We found that, with the tadasana maneuver, episodes of full syncope, where the patient actually loses consciousness, ceased completely, and episodes of near-syncope, where the patient feels faint but does not completely pass out, were greatly reduced,” Dr. Rao added. “The actual loss of consciousness, which is the most dangerous part, is practically gone. This gives a lot of confidence to patients and their families.”
The researchers reported their initial results from a pilot study of the technique in a letter to JACC: Clinical Electrophysiology that was published online Jan. 26, 2022.
Dr. Rao, a cardiologist at the KIMS Hospitals, Hyderabad, India, explained that vasovagal syncope is a brief loss of consciousness caused by a neurologically induced drop in blood pressure caused by faulty neuromuscular reflexes.
It is typically triggered by emotional stress, prolonged standing, or getting up from a sitting position too quickly.
Very few treatments have been shown effective, with current management approaches involving avoiding triggers, increasing fluids, and if the individual feels an episode coming on, they can take steps to stop it by lying down, raising their legs, or lowering their head to increase blood flow to the brain.
“Recently, there has been a lot of interest in yoga as a preventative therapy for vasovagal syncope,” Dr. Rao noted. “We considered various yoga positions and we chose the tadasana maneuver to study in this context as it resembles exercises sometimes given to patients with vasovagal syncope but with some differences including the addition of synchronized breathing, which may help stabilize autonomic tone.”
For the tadasana maneuver, the individual stands straight with their feet together, arms by their side (against a wall if they need support), and alternatively lift the front and back part of their feet.
They first lift their toes with their weight resting on the ball of their feet, then after a few seconds they raise their heels with their weight on the front of the foot. Then after a few more seconds they lift their arms over their shoulders, stretching upward while standing on their toes.
These movements are synchronized with breathing exercises, with the individual taking a deep breath in as they lift their arms and breathing out again on lowering the arms.
“Each movement takes a few seconds, and each cycle of movements takes about 2 minutes. If this is performed 8 times, then this would take about 15 minutes. We recommend this 15-minute routine twice a day,” Dr. Rao said.
For the current study, 113 patients diagnosed with recurrent vasovagal disorder were counseled to practice standard physical maneuvers and maintain adequate hydration. Medications were prescribed at the discretion of the treating physician.
Of these, 61 patients were additionally trained to practice the tadasana maneuver and asked to practice the movement for 15 minutes twice a day. The mean durations of symptoms and follow-up in the two groups were similar. The average follow-up was about 20 months.
Results showed that episodes of both near-syncope and syncope decreased in both groups but there was a much larger reduction in the patients practicing the tadasana maneuver.
Before treatment, the 52 patients in the conventional group experienced 163 syncope or near-syncope events. At follow-up, 22 symptom recurrences occurred in 12 patients (23%). Total mean events per patient declined from 3 to 0.4.
Full syncope events in this group declined from 65 in 32 patients to 2 in 2 patients (mean per patient, 1.3 to 1), and near-syncope events fell from 98 in 34 patients to 20 in 10 patients (mean per patient, 2.0 to 0.4).
In the tadasana group, 61 patients had 378 syncope/near-syncope events before treatment; at follow-up, only 6 events occurred in 5 patients (8%). Per patient, total events declined from a mean of 6 to 0.1.
Full syncope events fell from 108 in 48 patients to 0 (mean per patient, 1.8 to 0), and near-syncope events declined from 269 in 33 patients to 6 in 5 patients (mean per patient, 4.4 to 0.1).
“This combination of exercise and breathing influences the neuromuscular reflex malfunction that occurs in vasovagal syncope,” Dr. Rao noted. “The movements focus on strengthening neuromuscular reflexes in the quadriceps and the calf muscles, which can increase the blood circulation and venous return, thus preventing blood pooling in the lower body.”
The researchers said this pilot study offers three main findings. First, both conventional therapy and conventional plus tadasana therapy appeared to benefit patients, compared with their respective baseline symptom burden. Second, application of tadasana as an adjunctive treatment was associated with fewer total event recurrences (that is, syncope and near-syncope combined), and third, tadasana was well tolerated, with no adverse events reported.
“The reduction in total events (i.e., syncope and near-syncope events), compared with pretreatment numbers, was substantial and most tadasana patients were managed without any pharmacotherapy,” the authors reported.
Dr. Rao noted that at baseline almost all patients in both groups were taking medications for the condition, but during the study these medications were reduced as fewer episodes occurred. At the end of the follow-up, 80% of the conventional group were still taking medication, compared with just 14% of those in the tadasana group.
Patients had an initial training session in person with a yoga instructor and then received follow-on training by video online. Dr. Rao said there was a very high rate of compliance, “almost 100%.”
He reports that a total of 200 patients have now been treated with this approach at his hospital with very similar results to those seen in the initial study.
This work was supported in part by a grant from the Dr Earl E. Bakken Family in support of heart-brain research. Dr. Rao disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JACC: CLINICAL ELECTROPHYSIOLOGY
Oral penicillin advised for high-risk rheumatic heart disease
Some patients with rheumatic heart disease who are thought to have an allergic response to injectable penicillin may actually be experiencing a cardiac reaction to the injection, new information suggests.
This has resulted in new advice from the American Heart Association suggesting that oral penicillin may be a safer option for people with rheumatic heart disease who are at high risk of a cardiac reaction.
Those at high risk of a cardiac reaction include those with rheumatic heart disease and severe valvular heart disease with or without reduced ventricular function, those with aortic insufficiency or decreased left ventricular systolic function, and those who have active symptoms of rheumatic heart disease.
This new guidance is the subject of an AHA “presidential advisory” published online in the Journal of the American Heart Association on Jan. 20, 2022.
The advisory notes that more than 39 million people worldwide have rheumatic heart disease, a condition in which the heart’s valves are permanently damaged by rheumatic fever, which can occur if a strep throat infection or scarlet fever is untreated or inadequately treated.
Most cases of rheumatic heart disease occur in people living in low- and middle-income countries, where the condition is often diagnosed after severe valvular heart disease or other cardiovascular complications have already developed, leading to higher rates of death and lower life expectancy.
The recommended treatment for rheumatic heart disease is an intramuscular injection of benzathine penicillin G (BPG) given every 3-4 weeks for many years or even lifelong. Treatment with BPG for rheumatic heart disease has been limited in part because of patients’ and clinicians’ fears of anaphylaxis.
However, a growing number of reports of BPG-related deaths have not shown the features of classic anaphylaxis and instead point to a cardiovascular reaction, specifically, a vasovagal episode, the advisory states.
Signs of a vasovagal episode often occur immediately after administration of BPG, sometimes even during injection, and include low blood pressure, which can improve if patients are put into a supine position, slow heart rate, and fainting, all of which may lead to low blood flow to the heart, irregular heart rhythm, and sudden cardiac death.
On the other hand, signs of anaphylaxis after BPG injection are usually slightly delayed after the injection, even up to an hour later, and include coughing, respiratory distress, rapid heart rate, low blood pressure that doesn’t respond to position change, fainting, itching and redness at the injection site, the document notes.
The risks of a cardiovascular reaction to BPG are highest among individuals with severe mitral stenosis, aortic stenosis, aortic insufficiency or decreased left ventricular systolic function (ejection fraction <50%), and those who have active symptoms of rheumatic heart disease. For these patients, treatment with oral penicillin should be strongly considered.
People with rheumatic heart disease who are at low risk of this cardiovascular reaction and who do not have a history of being allergic to penicillin or anaphylaxis can still be prescribed BPG for treatment and prevention of rheumatic heart disease, which has been proven to be the best treatment for prevention of recurrent rheumatic fever.
The advisory recommended the following standard practices for all patients receiving BPG for rheumatic heart disease:
- Reducing injection pain and patient anxiety, both of which are known risk factors for injection-related fainting. Methods for pain reduction include applying firm pressure to the site for 10 seconds or application of an ice pack or the use of analgesics (such as acetaminophen, ibuprofen, or other NSAIDs).
- Patients should be well hydrated prior to injection and should drink at least 500 mL of water before injection to prevent reflexive fainting.
- Eating a small amount of solid food within the hour before injection.
- Receiving the injection while lying down, which may reduce the risk of blood pooling in the extremities.
- Providers who administer BPG should be taught how to recognize and quickly treat symptoms such as low blood pressure, low heart rate, or fainting.
A version of this article first appeared on Medscape.com.
Some patients with rheumatic heart disease who are thought to have an allergic response to injectable penicillin may actually be experiencing a cardiac reaction to the injection, new information suggests.
This has resulted in new advice from the American Heart Association suggesting that oral penicillin may be a safer option for people with rheumatic heart disease who are at high risk of a cardiac reaction.
Those at high risk of a cardiac reaction include those with rheumatic heart disease and severe valvular heart disease with or without reduced ventricular function, those with aortic insufficiency or decreased left ventricular systolic function, and those who have active symptoms of rheumatic heart disease.
This new guidance is the subject of an AHA “presidential advisory” published online in the Journal of the American Heart Association on Jan. 20, 2022.
The advisory notes that more than 39 million people worldwide have rheumatic heart disease, a condition in which the heart’s valves are permanently damaged by rheumatic fever, which can occur if a strep throat infection or scarlet fever is untreated or inadequately treated.
Most cases of rheumatic heart disease occur in people living in low- and middle-income countries, where the condition is often diagnosed after severe valvular heart disease or other cardiovascular complications have already developed, leading to higher rates of death and lower life expectancy.
The recommended treatment for rheumatic heart disease is an intramuscular injection of benzathine penicillin G (BPG) given every 3-4 weeks for many years or even lifelong. Treatment with BPG for rheumatic heart disease has been limited in part because of patients’ and clinicians’ fears of anaphylaxis.
However, a growing number of reports of BPG-related deaths have not shown the features of classic anaphylaxis and instead point to a cardiovascular reaction, specifically, a vasovagal episode, the advisory states.
Signs of a vasovagal episode often occur immediately after administration of BPG, sometimes even during injection, and include low blood pressure, which can improve if patients are put into a supine position, slow heart rate, and fainting, all of which may lead to low blood flow to the heart, irregular heart rhythm, and sudden cardiac death.
On the other hand, signs of anaphylaxis after BPG injection are usually slightly delayed after the injection, even up to an hour later, and include coughing, respiratory distress, rapid heart rate, low blood pressure that doesn’t respond to position change, fainting, itching and redness at the injection site, the document notes.
The risks of a cardiovascular reaction to BPG are highest among individuals with severe mitral stenosis, aortic stenosis, aortic insufficiency or decreased left ventricular systolic function (ejection fraction <50%), and those who have active symptoms of rheumatic heart disease. For these patients, treatment with oral penicillin should be strongly considered.
People with rheumatic heart disease who are at low risk of this cardiovascular reaction and who do not have a history of being allergic to penicillin or anaphylaxis can still be prescribed BPG for treatment and prevention of rheumatic heart disease, which has been proven to be the best treatment for prevention of recurrent rheumatic fever.
The advisory recommended the following standard practices for all patients receiving BPG for rheumatic heart disease:
- Reducing injection pain and patient anxiety, both of which are known risk factors for injection-related fainting. Methods for pain reduction include applying firm pressure to the site for 10 seconds or application of an ice pack or the use of analgesics (such as acetaminophen, ibuprofen, or other NSAIDs).
- Patients should be well hydrated prior to injection and should drink at least 500 mL of water before injection to prevent reflexive fainting.
- Eating a small amount of solid food within the hour before injection.
- Receiving the injection while lying down, which may reduce the risk of blood pooling in the extremities.
- Providers who administer BPG should be taught how to recognize and quickly treat symptoms such as low blood pressure, low heart rate, or fainting.
A version of this article first appeared on Medscape.com.
Some patients with rheumatic heart disease who are thought to have an allergic response to injectable penicillin may actually be experiencing a cardiac reaction to the injection, new information suggests.
This has resulted in new advice from the American Heart Association suggesting that oral penicillin may be a safer option for people with rheumatic heart disease who are at high risk of a cardiac reaction.
Those at high risk of a cardiac reaction include those with rheumatic heart disease and severe valvular heart disease with or without reduced ventricular function, those with aortic insufficiency or decreased left ventricular systolic function, and those who have active symptoms of rheumatic heart disease.
This new guidance is the subject of an AHA “presidential advisory” published online in the Journal of the American Heart Association on Jan. 20, 2022.
The advisory notes that more than 39 million people worldwide have rheumatic heart disease, a condition in which the heart’s valves are permanently damaged by rheumatic fever, which can occur if a strep throat infection or scarlet fever is untreated or inadequately treated.
Most cases of rheumatic heart disease occur in people living in low- and middle-income countries, where the condition is often diagnosed after severe valvular heart disease or other cardiovascular complications have already developed, leading to higher rates of death and lower life expectancy.
The recommended treatment for rheumatic heart disease is an intramuscular injection of benzathine penicillin G (BPG) given every 3-4 weeks for many years or even lifelong. Treatment with BPG for rheumatic heart disease has been limited in part because of patients’ and clinicians’ fears of anaphylaxis.
However, a growing number of reports of BPG-related deaths have not shown the features of classic anaphylaxis and instead point to a cardiovascular reaction, specifically, a vasovagal episode, the advisory states.
Signs of a vasovagal episode often occur immediately after administration of BPG, sometimes even during injection, and include low blood pressure, which can improve if patients are put into a supine position, slow heart rate, and fainting, all of which may lead to low blood flow to the heart, irregular heart rhythm, and sudden cardiac death.
On the other hand, signs of anaphylaxis after BPG injection are usually slightly delayed after the injection, even up to an hour later, and include coughing, respiratory distress, rapid heart rate, low blood pressure that doesn’t respond to position change, fainting, itching and redness at the injection site, the document notes.
The risks of a cardiovascular reaction to BPG are highest among individuals with severe mitral stenosis, aortic stenosis, aortic insufficiency or decreased left ventricular systolic function (ejection fraction <50%), and those who have active symptoms of rheumatic heart disease. For these patients, treatment with oral penicillin should be strongly considered.
People with rheumatic heart disease who are at low risk of this cardiovascular reaction and who do not have a history of being allergic to penicillin or anaphylaxis can still be prescribed BPG for treatment and prevention of rheumatic heart disease, which has been proven to be the best treatment for prevention of recurrent rheumatic fever.
The advisory recommended the following standard practices for all patients receiving BPG for rheumatic heart disease:
- Reducing injection pain and patient anxiety, both of which are known risk factors for injection-related fainting. Methods for pain reduction include applying firm pressure to the site for 10 seconds or application of an ice pack or the use of analgesics (such as acetaminophen, ibuprofen, or other NSAIDs).
- Patients should be well hydrated prior to injection and should drink at least 500 mL of water before injection to prevent reflexive fainting.
- Eating a small amount of solid food within the hour before injection.
- Receiving the injection while lying down, which may reduce the risk of blood pooling in the extremities.
- Providers who administer BPG should be taught how to recognize and quickly treat symptoms such as low blood pressure, low heart rate, or fainting.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Hypertension protocols curb racial bias in therapeutic inertia
Therapeutic inertia regarding intensification of blood pressure treatment has been shown to be more of an issue in Black patients, but this was not the case in the SPRINT trial, which involved a strict standardized approach to blood pressure management, a new analysis shows.
“Overall, we found that therapeutic inertia was similar in different races in the SPRINT trial. We did not see disparities that have been reported in previous observational studies,” lead author, Alexander Zheutlin, MD, University of Utah School of Medicine, Salt Lake City, told this news organization.
“These results show that a well-resourced approach in which a standardized approach to blood pressure measurement and treatment intensification is followed can overcome the racial disparity that is seen in therapeutic inertia and the treatment of blood pressure,” he added.
The study was published online in JAMA Network Open on Jan. 10.
The authors explain that hypertension remains a leading modifiable cause of racial disparities in cardiovascular disease. Despite similar treatment rates and increased availability of safe, effective, and affordable antihypertensive medications, blood pressure control rates among Black and Hispanic adults remain significantly lower than among White adults in the United States, and one of the factors contributing to this is thought to be therapeutic inertia – the phenomenon of clinicians not initiating or up-titrating clinically indicated therapy in the setting of unmet treatment goals.
The current analysis of the SPRINT trial was conducted to investigate whether racial and ethnic differences in therapeutic inertia in hypertension were present when blood pressure care was standardized and protocolized.
The landmark SPRINT trial compared intensive (<120 mm Hg) with standard (<140 mm Hg) systolic blood pressure treatment goals in adults 50 years and older at high risk for cardiovascular disease. The present analysis was restricted to participant visits with measured blood pressure above the target goal and included 4,141 patients in the standard group and 4,415 patients in the intensive group.
Results showed that the overall prevalence of therapeutic inertia – defined as no antihypertensive medication intensification at each study visit where the blood pressure was above target goal – was either similar or lower for Black and Hispanic participants than for White participants. This pattern was observed whether participants were randomized to the standard or intensive treatment group.
“These findings support the idea that a standardized approach to blood pressure management, as implemented in SPRINT, may help ensure equitable care is provided to all patients and could reduce the contribution of therapeutic inertia to disparities in uncontrolled blood pressure,” the authors say.
They point out that therapeutic inertia has been identified as a key clinician-level barrier to blood pressure control and is estimated to be present in more than 80% of clinic visits in community practice, whereas in the current analysis of the SPRINT trial, therapeutic inertia was present in 50% to 60% of participant visits with uncontrolled blood pressure.
“In SPRINT, blood pressure had to be measured at defined intervals with a specific method, and there were clear instructions on intensifying treatment if blood pressure was above a certain goal,” Dr. Zheutlin noted. “Our results show that within such strict confines, therapeutic inertia does not seem to be different between different racial groups. This suggests that we could make better gains in blood pressure control and more equitable treatment if we adopted a standardized approach to hypertension management.”
He added: “Many guidelines have been published on when to start treatment and the targets for blood pressure, but there is a lot of variation in how we turn these guidelines into protocols. We need to bring in more consistent protocols on blood pressure measurement and intensification and ensure they are followed. In practice, if the BP is 5 or 10 mm Hg above target, a clinician may defer a decision to intensify treatment and intensification never gets done. But if there was a strict protocol to follow, there would be less chance of this happening.”
Therapeutic inertia still high
In an accompanying commentary, Matthew Rivara, MD, Nisha Bansal, MD, and Bessie Young, MD, University of Washington, Seattle, say the current SPRINT analysis has broad implications for reducing racial and ethnic disparities in achievement of evidence-based treatment targets in the general population.
“In hypertension management, standardized protocols for medication adjustments may limit clinician practice heterogeneity to ultimately reduce differences in blood pressure control among racial and ethnic minority populations,” they write. But they add that such protocols must be implemented thoughtfully to incorporate individualized clinical assessment and clinician-patient shared decision-making.
Dr. Rivara et al. point out that the rates of therapeutic inertia in SPRINT, while lower than community-based estimates, were still very high. They suggest reasons for this could include clinician concerns about medication efficacy, adverse effects, and patient mistrust of medical professionals. Outside the clinical trial environment, additional considerations may include prescription drug and laboratory test costs, pharmacy access, and competing demands during busy clinic visits.
To address these challenges, they say that clinicians need education on current clinical practice guidelines, managing complications of intensified antihypertensive therapies, and shared decisionmaking, including culturally sensitive collaborative care. Similarly, care systems must support patients on how to address concerns about treatments.
Finally, further research is needed to better define the specific factors associated with therapeutic inertia to allow tailored interventions to overcome this inertia.
“In designing and performing such research, it is vital that investigators engage with racial and ethnic minority groups to better explore the intersection of race, ethnicity, therapeutic decision-making, trust, and shared decisionmaking,” they add.
The SPRINT trial was funded with federal funds from the National Institutes of Health. Dr. Zheutlin reported receiving grants from the NIH during the conduct of the study.
A version of this article first appeared on Medscape.com.
Therapeutic inertia regarding intensification of blood pressure treatment has been shown to be more of an issue in Black patients, but this was not the case in the SPRINT trial, which involved a strict standardized approach to blood pressure management, a new analysis shows.
“Overall, we found that therapeutic inertia was similar in different races in the SPRINT trial. We did not see disparities that have been reported in previous observational studies,” lead author, Alexander Zheutlin, MD, University of Utah School of Medicine, Salt Lake City, told this news organization.
“These results show that a well-resourced approach in which a standardized approach to blood pressure measurement and treatment intensification is followed can overcome the racial disparity that is seen in therapeutic inertia and the treatment of blood pressure,” he added.
The study was published online in JAMA Network Open on Jan. 10.
The authors explain that hypertension remains a leading modifiable cause of racial disparities in cardiovascular disease. Despite similar treatment rates and increased availability of safe, effective, and affordable antihypertensive medications, blood pressure control rates among Black and Hispanic adults remain significantly lower than among White adults in the United States, and one of the factors contributing to this is thought to be therapeutic inertia – the phenomenon of clinicians not initiating or up-titrating clinically indicated therapy in the setting of unmet treatment goals.
The current analysis of the SPRINT trial was conducted to investigate whether racial and ethnic differences in therapeutic inertia in hypertension were present when blood pressure care was standardized and protocolized.
The landmark SPRINT trial compared intensive (<120 mm Hg) with standard (<140 mm Hg) systolic blood pressure treatment goals in adults 50 years and older at high risk for cardiovascular disease. The present analysis was restricted to participant visits with measured blood pressure above the target goal and included 4,141 patients in the standard group and 4,415 patients in the intensive group.
Results showed that the overall prevalence of therapeutic inertia – defined as no antihypertensive medication intensification at each study visit where the blood pressure was above target goal – was either similar or lower for Black and Hispanic participants than for White participants. This pattern was observed whether participants were randomized to the standard or intensive treatment group.
“These findings support the idea that a standardized approach to blood pressure management, as implemented in SPRINT, may help ensure equitable care is provided to all patients and could reduce the contribution of therapeutic inertia to disparities in uncontrolled blood pressure,” the authors say.
They point out that therapeutic inertia has been identified as a key clinician-level barrier to blood pressure control and is estimated to be present in more than 80% of clinic visits in community practice, whereas in the current analysis of the SPRINT trial, therapeutic inertia was present in 50% to 60% of participant visits with uncontrolled blood pressure.
“In SPRINT, blood pressure had to be measured at defined intervals with a specific method, and there were clear instructions on intensifying treatment if blood pressure was above a certain goal,” Dr. Zheutlin noted. “Our results show that within such strict confines, therapeutic inertia does not seem to be different between different racial groups. This suggests that we could make better gains in blood pressure control and more equitable treatment if we adopted a standardized approach to hypertension management.”
He added: “Many guidelines have been published on when to start treatment and the targets for blood pressure, but there is a lot of variation in how we turn these guidelines into protocols. We need to bring in more consistent protocols on blood pressure measurement and intensification and ensure they are followed. In practice, if the BP is 5 or 10 mm Hg above target, a clinician may defer a decision to intensify treatment and intensification never gets done. But if there was a strict protocol to follow, there would be less chance of this happening.”
Therapeutic inertia still high
In an accompanying commentary, Matthew Rivara, MD, Nisha Bansal, MD, and Bessie Young, MD, University of Washington, Seattle, say the current SPRINT analysis has broad implications for reducing racial and ethnic disparities in achievement of evidence-based treatment targets in the general population.
“In hypertension management, standardized protocols for medication adjustments may limit clinician practice heterogeneity to ultimately reduce differences in blood pressure control among racial and ethnic minority populations,” they write. But they add that such protocols must be implemented thoughtfully to incorporate individualized clinical assessment and clinician-patient shared decision-making.
Dr. Rivara et al. point out that the rates of therapeutic inertia in SPRINT, while lower than community-based estimates, were still very high. They suggest reasons for this could include clinician concerns about medication efficacy, adverse effects, and patient mistrust of medical professionals. Outside the clinical trial environment, additional considerations may include prescription drug and laboratory test costs, pharmacy access, and competing demands during busy clinic visits.
To address these challenges, they say that clinicians need education on current clinical practice guidelines, managing complications of intensified antihypertensive therapies, and shared decisionmaking, including culturally sensitive collaborative care. Similarly, care systems must support patients on how to address concerns about treatments.
Finally, further research is needed to better define the specific factors associated with therapeutic inertia to allow tailored interventions to overcome this inertia.
“In designing and performing such research, it is vital that investigators engage with racial and ethnic minority groups to better explore the intersection of race, ethnicity, therapeutic decision-making, trust, and shared decisionmaking,” they add.
The SPRINT trial was funded with federal funds from the National Institutes of Health. Dr. Zheutlin reported receiving grants from the NIH during the conduct of the study.
A version of this article first appeared on Medscape.com.
Therapeutic inertia regarding intensification of blood pressure treatment has been shown to be more of an issue in Black patients, but this was not the case in the SPRINT trial, which involved a strict standardized approach to blood pressure management, a new analysis shows.
“Overall, we found that therapeutic inertia was similar in different races in the SPRINT trial. We did not see disparities that have been reported in previous observational studies,” lead author, Alexander Zheutlin, MD, University of Utah School of Medicine, Salt Lake City, told this news organization.
“These results show that a well-resourced approach in which a standardized approach to blood pressure measurement and treatment intensification is followed can overcome the racial disparity that is seen in therapeutic inertia and the treatment of blood pressure,” he added.
The study was published online in JAMA Network Open on Jan. 10.
The authors explain that hypertension remains a leading modifiable cause of racial disparities in cardiovascular disease. Despite similar treatment rates and increased availability of safe, effective, and affordable antihypertensive medications, blood pressure control rates among Black and Hispanic adults remain significantly lower than among White adults in the United States, and one of the factors contributing to this is thought to be therapeutic inertia – the phenomenon of clinicians not initiating or up-titrating clinically indicated therapy in the setting of unmet treatment goals.
The current analysis of the SPRINT trial was conducted to investigate whether racial and ethnic differences in therapeutic inertia in hypertension were present when blood pressure care was standardized and protocolized.
The landmark SPRINT trial compared intensive (<120 mm Hg) with standard (<140 mm Hg) systolic blood pressure treatment goals in adults 50 years and older at high risk for cardiovascular disease. The present analysis was restricted to participant visits with measured blood pressure above the target goal and included 4,141 patients in the standard group and 4,415 patients in the intensive group.
Results showed that the overall prevalence of therapeutic inertia – defined as no antihypertensive medication intensification at each study visit where the blood pressure was above target goal – was either similar or lower for Black and Hispanic participants than for White participants. This pattern was observed whether participants were randomized to the standard or intensive treatment group.
“These findings support the idea that a standardized approach to blood pressure management, as implemented in SPRINT, may help ensure equitable care is provided to all patients and could reduce the contribution of therapeutic inertia to disparities in uncontrolled blood pressure,” the authors say.
They point out that therapeutic inertia has been identified as a key clinician-level barrier to blood pressure control and is estimated to be present in more than 80% of clinic visits in community practice, whereas in the current analysis of the SPRINT trial, therapeutic inertia was present in 50% to 60% of participant visits with uncontrolled blood pressure.
“In SPRINT, blood pressure had to be measured at defined intervals with a specific method, and there were clear instructions on intensifying treatment if blood pressure was above a certain goal,” Dr. Zheutlin noted. “Our results show that within such strict confines, therapeutic inertia does not seem to be different between different racial groups. This suggests that we could make better gains in blood pressure control and more equitable treatment if we adopted a standardized approach to hypertension management.”
He added: “Many guidelines have been published on when to start treatment and the targets for blood pressure, but there is a lot of variation in how we turn these guidelines into protocols. We need to bring in more consistent protocols on blood pressure measurement and intensification and ensure they are followed. In practice, if the BP is 5 or 10 mm Hg above target, a clinician may defer a decision to intensify treatment and intensification never gets done. But if there was a strict protocol to follow, there would be less chance of this happening.”
Therapeutic inertia still high
In an accompanying commentary, Matthew Rivara, MD, Nisha Bansal, MD, and Bessie Young, MD, University of Washington, Seattle, say the current SPRINT analysis has broad implications for reducing racial and ethnic disparities in achievement of evidence-based treatment targets in the general population.
“In hypertension management, standardized protocols for medication adjustments may limit clinician practice heterogeneity to ultimately reduce differences in blood pressure control among racial and ethnic minority populations,” they write. But they add that such protocols must be implemented thoughtfully to incorporate individualized clinical assessment and clinician-patient shared decision-making.
Dr. Rivara et al. point out that the rates of therapeutic inertia in SPRINT, while lower than community-based estimates, were still very high. They suggest reasons for this could include clinician concerns about medication efficacy, adverse effects, and patient mistrust of medical professionals. Outside the clinical trial environment, additional considerations may include prescription drug and laboratory test costs, pharmacy access, and competing demands during busy clinic visits.
To address these challenges, they say that clinicians need education on current clinical practice guidelines, managing complications of intensified antihypertensive therapies, and shared decisionmaking, including culturally sensitive collaborative care. Similarly, care systems must support patients on how to address concerns about treatments.
Finally, further research is needed to better define the specific factors associated with therapeutic inertia to allow tailored interventions to overcome this inertia.
“In designing and performing such research, it is vital that investigators engage with racial and ethnic minority groups to better explore the intersection of race, ethnicity, therapeutic decision-making, trust, and shared decisionmaking,” they add.
The SPRINT trial was funded with federal funds from the National Institutes of Health. Dr. Zheutlin reported receiving grants from the NIH during the conduct of the study.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Cardiac inflammation can be present after mild COVID infection
Myocardial inflammation is present in a small proportion of patients who have recovered from relatively mild cases of COVID-19 infection, a new study shows.
“Our findings suggest that even in patients who have had relatively mild cases of COVID-19, some will have inflammatory changes to the heart, and these changes can be present without any cardiac symptoms,” senior author, Paaladinesh Thavendiranathan, MD, University of Toronto, told this news organization.
“While our data suggest that this inflammation improves over time, and the outcomes seem positive, we don’t know if there will be any long-term consequences,” he added.
Noting that even a short period of inflammation in the heart may be associated with symptoms or arrhythmias in the longer term, Dr. Thavendiranathan said: “I would recommend that it is best to avoid getting the infection if there is any chance of heart inflammation.”
The study was published online in JAMA Cardiology on Jan. 12.
The authors explain that among patients hospitalized with COVID, early studies suggested that approximately one in four experience cardiovascular injury, defined as an elevation in troponin levels, which was associated with a 5- to 10-fold increase in the risk for death. But there is limited information on cardiac injury in patients who do not require hospitalization.
Although a broad range of abnormal myocardial tissue has been reported in several cardiac MRI studies of patients recovered from COVID infection, there is little understanding of persistent changes in myocardial metabolism in recovered patients, which is a potential concern, given that COVID-19 is associated with systemic inflammation during the acute illness, they say.
For the current study, the researchers examined myocardial inflammation measured using two different methods – cardiac MRI and fluorodeoxyglucose–positron emission tomography (FDG-PET) – in individuals who had recovered from COVID-19 infection and looked at how this related to changes in inflammatory blood markers.
Lead author Kate Hanneman, MD, also from the University of Toronto, explained that FDG-PET imaging is more sensitive than MRI in detecting active inflammation. “Inflammatory cells have a higher uptake of glucose, and FDG-PET imaging is used to look for metabolically active inflammatory tissue that takes up glucose. It gives complementary information to MRI. Cardiac MRI shows structural or functional changes, such as scarring or edema, whereas FDG-PET imaging directly measures metabolic activity related to inflammatory cells.”
The study involved 47 individuals, 51% female, with a mean age of 43 years, who had recently recovered from COVID-19 infection. Of these, the majority had had relatively mild COVID disease, with 85% not requiring hospitalization.
Cardiac imaging was performed a mean of 67 days after the diagnosis of COVID-19. At the time of imaging, 19 participants (40%) reported at least one cardiac symptom, including palpitations, chest pain, and shortness of breath.
Results showed that eight patients (17%) had focal FDG uptake on PET consistent with myocardial inflammation. Compared with those without FDG uptake, patients with focal FDG uptake had higher regional T2, T1, and extracellular volume (colocalizing with focal FDG uptake), higher prevalence of late gadolinium enhancement indicating fibrosis, lower left ventricular ejection fraction, worse global longitudinal and circumferential strain, and higher systemic inflammatory blood markers, including interleukin (IL)-6, IL- 8, an high-sensitivity C-reactive protein.
Of the 47 patients in the study, 13 had received at least one dose of a COVID-19 vaccine. There was no significant difference in the proportion of patients who were PET-positive among those who had received a COVID-19 vaccine and those who had not.
There was also no difference in inflammation in patients who had been hospitalized with COVID-19 and those who had managed their infection at home.
Among patients with focal FDG uptake, PET, MRI, and inflammatory blood markers improved at follow-up imaging performed a mean of 52 days after the first imaging. The authors say this suggests that these abnormalities were not related to pre-existing cardiovascular disease.
Of the eight patients with positive FDG-PET results, two did not show any MRI abnormalities. These two patients also had elevated inflammatory biomarkers. “PET is a more sensitive method of measuring cardiac inflammation, and our results show that these changes may not always translate into functional changes seen on MRI,” Dr. Thavendiranathan noted.
The only cardiac risk factor that was more common in participants with FDG uptake was hypertension. Although cardiac symptoms were nearly twice as common in participants with focal FDG uptake, this difference was not statistically significant.
“Given the growing number of survivors with similar symptoms, these interesting findings warrant further investigation,” the authors say.
Noting that FDG uptake correlated with elevations in systemic inflammatory biomarkers, the researchers suggest that “a more intense systemic inflammatory process may be contributing to cardiac inflammation and the consequential alteration to regional and global myocardial function in PET-positive participants.”
On repeat imaging 2 months later, all eight patients who showed FDG uptake showed improvement or resolution of inflammation without any treatment, although two patients still had some signs of inflammation. Blood biomarkers also improved on follow-up.
“This is encouraging information, but we need longer-term data to see if there are any long-term repercussions of this inflammation,” Dr. Hanneman said.
“Overall, the study findings suggest an imaging phenotype that is expected to have good prognosis. However, longer-term follow-up studies are required to understand the need for ongoing cardiac surveillance, relationship to cardiac symptoms, guidance for safe return to exercise and sports participation, and long-term cardiovascular disease risk,” the researchers state.
This study was funded by grants from the Joint Department of Medical Imaging Academic Incentive Fund, Peter Munk Cardiac Center Innovation Committee, and Ted Rogers Center for Heart Research. Dr. Hanneman reports personal fees from Sanofi Genzyme, Amicus, and Medscape outside the submitted work.
A version of this article first appeared on Medscape.com.
Myocardial inflammation is present in a small proportion of patients who have recovered from relatively mild cases of COVID-19 infection, a new study shows.
“Our findings suggest that even in patients who have had relatively mild cases of COVID-19, some will have inflammatory changes to the heart, and these changes can be present without any cardiac symptoms,” senior author, Paaladinesh Thavendiranathan, MD, University of Toronto, told this news organization.
“While our data suggest that this inflammation improves over time, and the outcomes seem positive, we don’t know if there will be any long-term consequences,” he added.
Noting that even a short period of inflammation in the heart may be associated with symptoms or arrhythmias in the longer term, Dr. Thavendiranathan said: “I would recommend that it is best to avoid getting the infection if there is any chance of heart inflammation.”
The study was published online in JAMA Cardiology on Jan. 12.
The authors explain that among patients hospitalized with COVID, early studies suggested that approximately one in four experience cardiovascular injury, defined as an elevation in troponin levels, which was associated with a 5- to 10-fold increase in the risk for death. But there is limited information on cardiac injury in patients who do not require hospitalization.
Although a broad range of abnormal myocardial tissue has been reported in several cardiac MRI studies of patients recovered from COVID infection, there is little understanding of persistent changes in myocardial metabolism in recovered patients, which is a potential concern, given that COVID-19 is associated with systemic inflammation during the acute illness, they say.
For the current study, the researchers examined myocardial inflammation measured using two different methods – cardiac MRI and fluorodeoxyglucose–positron emission tomography (FDG-PET) – in individuals who had recovered from COVID-19 infection and looked at how this related to changes in inflammatory blood markers.
Lead author Kate Hanneman, MD, also from the University of Toronto, explained that FDG-PET imaging is more sensitive than MRI in detecting active inflammation. “Inflammatory cells have a higher uptake of glucose, and FDG-PET imaging is used to look for metabolically active inflammatory tissue that takes up glucose. It gives complementary information to MRI. Cardiac MRI shows structural or functional changes, such as scarring or edema, whereas FDG-PET imaging directly measures metabolic activity related to inflammatory cells.”
The study involved 47 individuals, 51% female, with a mean age of 43 years, who had recently recovered from COVID-19 infection. Of these, the majority had had relatively mild COVID disease, with 85% not requiring hospitalization.
Cardiac imaging was performed a mean of 67 days after the diagnosis of COVID-19. At the time of imaging, 19 participants (40%) reported at least one cardiac symptom, including palpitations, chest pain, and shortness of breath.
Results showed that eight patients (17%) had focal FDG uptake on PET consistent with myocardial inflammation. Compared with those without FDG uptake, patients with focal FDG uptake had higher regional T2, T1, and extracellular volume (colocalizing with focal FDG uptake), higher prevalence of late gadolinium enhancement indicating fibrosis, lower left ventricular ejection fraction, worse global longitudinal and circumferential strain, and higher systemic inflammatory blood markers, including interleukin (IL)-6, IL- 8, an high-sensitivity C-reactive protein.
Of the 47 patients in the study, 13 had received at least one dose of a COVID-19 vaccine. There was no significant difference in the proportion of patients who were PET-positive among those who had received a COVID-19 vaccine and those who had not.
There was also no difference in inflammation in patients who had been hospitalized with COVID-19 and those who had managed their infection at home.
Among patients with focal FDG uptake, PET, MRI, and inflammatory blood markers improved at follow-up imaging performed a mean of 52 days after the first imaging. The authors say this suggests that these abnormalities were not related to pre-existing cardiovascular disease.
Of the eight patients with positive FDG-PET results, two did not show any MRI abnormalities. These two patients also had elevated inflammatory biomarkers. “PET is a more sensitive method of measuring cardiac inflammation, and our results show that these changes may not always translate into functional changes seen on MRI,” Dr. Thavendiranathan noted.
The only cardiac risk factor that was more common in participants with FDG uptake was hypertension. Although cardiac symptoms were nearly twice as common in participants with focal FDG uptake, this difference was not statistically significant.
“Given the growing number of survivors with similar symptoms, these interesting findings warrant further investigation,” the authors say.
Noting that FDG uptake correlated with elevations in systemic inflammatory biomarkers, the researchers suggest that “a more intense systemic inflammatory process may be contributing to cardiac inflammation and the consequential alteration to regional and global myocardial function in PET-positive participants.”
On repeat imaging 2 months later, all eight patients who showed FDG uptake showed improvement or resolution of inflammation without any treatment, although two patients still had some signs of inflammation. Blood biomarkers also improved on follow-up.
“This is encouraging information, but we need longer-term data to see if there are any long-term repercussions of this inflammation,” Dr. Hanneman said.
“Overall, the study findings suggest an imaging phenotype that is expected to have good prognosis. However, longer-term follow-up studies are required to understand the need for ongoing cardiac surveillance, relationship to cardiac symptoms, guidance for safe return to exercise and sports participation, and long-term cardiovascular disease risk,” the researchers state.
This study was funded by grants from the Joint Department of Medical Imaging Academic Incentive Fund, Peter Munk Cardiac Center Innovation Committee, and Ted Rogers Center for Heart Research. Dr. Hanneman reports personal fees from Sanofi Genzyme, Amicus, and Medscape outside the submitted work.
A version of this article first appeared on Medscape.com.
Myocardial inflammation is present in a small proportion of patients who have recovered from relatively mild cases of COVID-19 infection, a new study shows.
“Our findings suggest that even in patients who have had relatively mild cases of COVID-19, some will have inflammatory changes to the heart, and these changes can be present without any cardiac symptoms,” senior author, Paaladinesh Thavendiranathan, MD, University of Toronto, told this news organization.
“While our data suggest that this inflammation improves over time, and the outcomes seem positive, we don’t know if there will be any long-term consequences,” he added.
Noting that even a short period of inflammation in the heart may be associated with symptoms or arrhythmias in the longer term, Dr. Thavendiranathan said: “I would recommend that it is best to avoid getting the infection if there is any chance of heart inflammation.”
The study was published online in JAMA Cardiology on Jan. 12.
The authors explain that among patients hospitalized with COVID, early studies suggested that approximately one in four experience cardiovascular injury, defined as an elevation in troponin levels, which was associated with a 5- to 10-fold increase in the risk for death. But there is limited information on cardiac injury in patients who do not require hospitalization.
Although a broad range of abnormal myocardial tissue has been reported in several cardiac MRI studies of patients recovered from COVID infection, there is little understanding of persistent changes in myocardial metabolism in recovered patients, which is a potential concern, given that COVID-19 is associated with systemic inflammation during the acute illness, they say.
For the current study, the researchers examined myocardial inflammation measured using two different methods – cardiac MRI and fluorodeoxyglucose–positron emission tomography (FDG-PET) – in individuals who had recovered from COVID-19 infection and looked at how this related to changes in inflammatory blood markers.
Lead author Kate Hanneman, MD, also from the University of Toronto, explained that FDG-PET imaging is more sensitive than MRI in detecting active inflammation. “Inflammatory cells have a higher uptake of glucose, and FDG-PET imaging is used to look for metabolically active inflammatory tissue that takes up glucose. It gives complementary information to MRI. Cardiac MRI shows structural or functional changes, such as scarring or edema, whereas FDG-PET imaging directly measures metabolic activity related to inflammatory cells.”
The study involved 47 individuals, 51% female, with a mean age of 43 years, who had recently recovered from COVID-19 infection. Of these, the majority had had relatively mild COVID disease, with 85% not requiring hospitalization.
Cardiac imaging was performed a mean of 67 days after the diagnosis of COVID-19. At the time of imaging, 19 participants (40%) reported at least one cardiac symptom, including palpitations, chest pain, and shortness of breath.
Results showed that eight patients (17%) had focal FDG uptake on PET consistent with myocardial inflammation. Compared with those without FDG uptake, patients with focal FDG uptake had higher regional T2, T1, and extracellular volume (colocalizing with focal FDG uptake), higher prevalence of late gadolinium enhancement indicating fibrosis, lower left ventricular ejection fraction, worse global longitudinal and circumferential strain, and higher systemic inflammatory blood markers, including interleukin (IL)-6, IL- 8, an high-sensitivity C-reactive protein.
Of the 47 patients in the study, 13 had received at least one dose of a COVID-19 vaccine. There was no significant difference in the proportion of patients who were PET-positive among those who had received a COVID-19 vaccine and those who had not.
There was also no difference in inflammation in patients who had been hospitalized with COVID-19 and those who had managed their infection at home.
Among patients with focal FDG uptake, PET, MRI, and inflammatory blood markers improved at follow-up imaging performed a mean of 52 days after the first imaging. The authors say this suggests that these abnormalities were not related to pre-existing cardiovascular disease.
Of the eight patients with positive FDG-PET results, two did not show any MRI abnormalities. These two patients also had elevated inflammatory biomarkers. “PET is a more sensitive method of measuring cardiac inflammation, and our results show that these changes may not always translate into functional changes seen on MRI,” Dr. Thavendiranathan noted.
The only cardiac risk factor that was more common in participants with FDG uptake was hypertension. Although cardiac symptoms were nearly twice as common in participants with focal FDG uptake, this difference was not statistically significant.
“Given the growing number of survivors with similar symptoms, these interesting findings warrant further investigation,” the authors say.
Noting that FDG uptake correlated with elevations in systemic inflammatory biomarkers, the researchers suggest that “a more intense systemic inflammatory process may be contributing to cardiac inflammation and the consequential alteration to regional and global myocardial function in PET-positive participants.”
On repeat imaging 2 months later, all eight patients who showed FDG uptake showed improvement or resolution of inflammation without any treatment, although two patients still had some signs of inflammation. Blood biomarkers also improved on follow-up.
“This is encouraging information, but we need longer-term data to see if there are any long-term repercussions of this inflammation,” Dr. Hanneman said.
“Overall, the study findings suggest an imaging phenotype that is expected to have good prognosis. However, longer-term follow-up studies are required to understand the need for ongoing cardiac surveillance, relationship to cardiac symptoms, guidance for safe return to exercise and sports participation, and long-term cardiovascular disease risk,” the researchers state.
This study was funded by grants from the Joint Department of Medical Imaging Academic Incentive Fund, Peter Munk Cardiac Center Innovation Committee, and Ted Rogers Center for Heart Research. Dr. Hanneman reports personal fees from Sanofi Genzyme, Amicus, and Medscape outside the submitted work.
A version of this article first appeared on Medscape.com.