Thrombosis

Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).

Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.

The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online  in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.

“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.

“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.

“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.

Time-honored treatments no more?

Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.

For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.

Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.

“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.

The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.

In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.

The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.

For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.

It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.

For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.

However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
 

Multidisciplinary care

For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.

Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.

Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.

“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.

The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
 

Opportunity for prevention?

The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.

While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.

“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.

“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.

“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.

The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.

This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.

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

Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).

Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.

The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online  in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.

“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.

“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.

“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.

Time-honored treatments no more?

Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.

For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.

Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.

“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.

The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.

In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.

The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.

For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.

It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.

For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.

However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
 

Multidisciplinary care

For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.

Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.

Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.

“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.

The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
 

Opportunity for prevention?

The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.

While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.

“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.

“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.

“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.

The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.

This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.

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

Many strategies widely considered “standard care” for managing spontaneous intracerebral hemorrhage (ICH) are not as effective as previously thought and are no longer recommended in updated guidelines from the American Heart Association/American Stroke Association (ASA).

Compression stockings, antiseizure medication, and steroid treatment are among the treatments with uncertain effectiveness, the writing group says.

The 2022 Guideline for the Management of Patients With Spontaneous ICH was published online  in Stroke. The 80-page document contains major changes and refinements to the 2015 guideline on ICH management.

“Advances have been made in an array of fields related to ICH, including the organization of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures, and the underlying disease in small blood vessels,” Steven M. Greenberg, MD, PhD, chair of the guideline writing group with Harvard Medical School and Massachusetts General Hospital, both in Boston, said in a news release.

“We’ve updated sections across the board. There’s probably no area that went untouched with some tweaking and new evidence added that led to some changes in level of evidence or strength of a recommendation,” Dr. Greenberg added in an interview with this news organization.

“Each section comes with knowledge gaps, and it wasn’t hard to come up with knowledge gaps in every section,” Dr. Greenberg acknowledged.

Time-honored treatments no more?

Among the key updates are changes to some “time-honored” treatments that continue to be used with some “regularity” for patients with ICH, yet appear to confer either no benefit or harm, Dr. Greenberg said.

For example, for emergency or critical care treatment of ICH, prophylactic corticosteroids or continuous hyperosmolar therapy is not recommended, because it appears to have no benefit for outcome, while use of platelet transfusions outside the setting of emergency surgery or severe thrombocytopenia appears to worsen outcome, the authors say.

Use of graduated knee- or thigh-high compression stockings alone is not an effective prophylactic therapy for prevention of deep vein thrombosis (DVT). Instead, intermittent pneumatic compression (IPC) starting on the day of diagnosis is now recommended for DVT prophylaxis.

“This is an area where we still have a lot of exploration to do. It is unclear whether even specialized compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed,” Dr. Greenberg said in the release.

The new guidance advises against use of antiseizure or antidepressant medications for ICH patients in whom there is no evidence of seizures or depression.

In clinical trials, antiseizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of antidepressants increased the chance of bone fractures, the authors say.

The guideline also provides updated recommendations for acute reversal of anticoagulation after ICH. It highlights the use of protein complex concentrate for reversal of vitamin K antagonists, such as warfarin; idarucizumab for reversal of the thrombin inhibitor dabigatran; and andexanet alfa for reversal of factor Xa inhibitors, such as rivaroxaban, apixaban, and edoxaban.

For acute blood pressure lowering after mild to moderate ICH, treatment regimens that limit blood pressure variability and achieve smooth, sustained blood pressure control appear to reduce hematoma expansion and yield better functional outcome, the guideline says.

It also notes that minimally invasive approaches for hematoma evacuation, compared with medical management alone‚ have been shown to reduce mortality.

For patients with cerebellar hemorrhage, indications for immediate surgical evacuation with or without an external ventricular drain to reduce mortality now include larger volume (> 15 mL) in addition to previously recommended indications of neurologic deterioration, brainstem compression, and hydrocephalus, the authors note.

However, a “major knowledge gap is whether we can improve functional outcome with hematoma evacuation,” Dr. Greenberg said.
 

Multidisciplinary care

For rehabilitation after ICH, the guideline reinforces the importance of having a multidisciplinary team to develop a comprehensive plan for recovery.

Starting rehabilitation activities such as stretching and functional task training may be considered 24 to 48 hours following mild or moderate ICH. However, early aggressive mobilization within the first 24 hours has been linked to an increased risk of death within 14 days after an ICH, the guideline says.

Knowledge gaps include how soon it’s safe to return to work, drive, and participate in other social engagements. Recommendations on sexual activity and exercise levels that are safe after a stroke are also needed.

“People need additional help with these lifestyle changes, whether it’s moving around more, curbing their alcohol use, or eating healthier foods. This all happens after they leave the hospital, and we need to be sure we are empowering families with the information they may need to be properly supportive,” Dr. Greenberg says in the release.

The guideline points to the patient’s home caregiver as a “key and sometimes overlooked” member of the care team. It recommends psychosocial education, practical support, and training for the caregiver to improve the patient’s balance, activity level, and overall quality of life.
 

Opportunity for prevention?

The guideline also suggests there may be an opportunity to prevent ICH in some people through neuroimaging markers.

While neuroimaging is not routinely performed as a part of risk stratification for primary ICH risk, damage to small blood vessels that is associated with ICH may be evident on MRI that could signal future ICH risk, the guideline says.

“We added to the guidelines for the first time a section on mostly imaging markers of risk for having a first-ever hemorrhage,” Dr. Greenberg said in an interview.

“We don’t make any recommendations as to how to act on these markers because there is a knowledge gap. The hope is that we’ll see growth in our ability to predict first-ever hemorrhage and be able to do things to prevent first-ever hemorrhage,” he said.

“We believe the wide range of knowledge set forth in the new guideline will translate into meaningful improvements in ICH care,” Dr. Greenberg adds in the release.

The updated guideline has been endorsed by the American Association of Neurological Surgeons and Congress of Neurological Surgeons, the Society of Vascular and Interventional Neurology, and the Neurocritical Care Society. The American Academy of Neurology has affirmed the value of this statement as an educational tool for neurologists.

This research had no commercial funding. Dr. Greenberg has disclosed no relevant financial relationships. A complete list of disclosures for the guideline group is available with the original article.

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

More than 70% of cancer patients do not know that they are at greater risk of deep vein thrombosis (DVT) than the general population. It is up to their physician to discuss this with them.

This link is explained by the authors of an article in Cancer Treatment and Research Communications that reports results of a survey carried out by the European Cancer Patient Coalition (ECPC). “The aim of this pan-European patient survey was to assess patient awareness and knowledge about cancer-associated thrombosis (CAT), including risk factors, signs and symptoms, and interventions, to better prevent and treat CAT,” write the authors. “The idea was to create a sort of starting point for subsequent communication and information strategies and for comparing the results of any action taken in this area,” they add.

A roundtable discussion that included oncology healthcare professionals, policymakers, and patient advocates was convened to discuss and review the evidence regarding their ongoing concerns of excessive CAT-associated morbidity and mortality, as well as patients’ desire for greater CAT awareness.

“These discussions demonstrated that very little change had occurred over the years and that greater knowledge about CAT was still needed across the spectrum of healthcare practitioners and patients, particularly regarding primary and secondary prevention of thrombosis,” the authors write.

It was from this starting point that the idea for the pan-European survey was born. The ECPC, widely viewed as the “unified voice of cancer patients across Europe,” led the survey. This survey spanned six countries (France, Germany, Greece, Italy, United Kingdom, and Spain) and involved 1,365 patients and caregivers. The ECPC survey result was originally released at World Thrombosis Day in late 2018.

In an interview, Anna Falanga, MD, the main author of the article and professor of hematology at the University of Milan-Bicocca, Italy, reviewed the results and explained how to improve knowledge of CAT among patients with cancer.

“Data support that up to 20% of patients with cancer will experience venous thromboembolism (VTE), which is approximately 4–5 times higher than the general population,” said Dr. Falanga, who is also chief of the department of immunohematology and transfusion medicine and the Thrombosis and Hemostasis Center at the Hospital Papa Giovanni XXIII, in Bergamo, Italy.

“We have known about the link between thrombosis and cancer since the 19th century, but it has taken until midway through the last century for our level of understanding and awareness of the problem to reach its current level. Initially, this was limited to fundamental research, with large advances in our understanding of the mechanisms of the link between the two; it has only been more recently that we have had clinical studies that have piqued the interest of healthcare professionals, who were previously uninterested in the topic,” she said.
 

Poor understanding

One piece of data stands out from the European survey: Nearly three quarters of respondents (72%) said that before taking part in the survey, they were not aware that people with cancer have a higher-than-normal risk of developing thrombosis. “We asked participants to rate their overall understanding of CAT on a scale of 1 (low) to 10 (high), with the average (mean) score obtained being 4.1. Only 21% of patients gave a rating of 7 or above (high understanding). The average rating was very similar in the different countries surveyed,” write the authors. They note that the survey also assessed how much participants had learned about the topic from their physicians.

Approximately 35% of patients were made aware of CAT either immediately before or at the time of their cancer diagnosis. Of particular concern, one quarter (26%) of respondents (the largest proportion) noted that they first became aware of CAT when they suffered a blood clot. The average rating was very similar in the different countries surveyed. “Let us not forget that cancer and cancer treatments themselves cause a number of side effects, some of which can be very serious, so in some ways, a clot might be seen as a minor problem. Yet, in reality, it isn’t. It is a significant cause of death and disease in cancer patients,” said Dr. Falanga.

When discussing prevention, most respondents (87%) said they were aware that taking a walk could reduce their risk. Slightly fewer were aware that stopping smoking could reduce their risk (75%), and even fewer were aware that keeping hydrated (63%) and stretching their legs (55%) could reduce their risk.

Symptoms of CAT appeared to be relatively well known; 73% of survey participants indicated that they were aware that swelling in the foot, ankle, or leg could be a sign of DVT, and 71% indicated that shortness of breath could be a sign of pulmonary embolism (PE). “Other symptoms, however, were less well known, with just over half (57%) of participants being aware that pain, cramping, and tenderness could be a sign of DVT. About one third (33%) knew that irregular heartbeat could be a sign of PE. These results varied between countries,” according to the authors.

The survey highlighted that just over a third of respondents said that they were currently using anticoagulants, although almost all (96%) knew that anticoagulants could be used to effectively treat thrombosis. Only 41% of those using anticoagulants said they had been told about any possible side effects.
 

The Italian situation

The report containing the full results of the European survey goes even further, since, in addition to its overall results, it also gives information about individual countries.

The data from Italy, which are based on 246 persons, show that only 27% of patients and caregivers were aware of the increased risk of thrombosis after a cancer diagnosis. This figure is in line with the overall results of the survey, although the average score of the 10-point scale was lower for the Italy cohort (3.3/10 vs 4.1/10).

The results are more variable in terms of knowledge of risk factors. Most respondents (89%) said that they were aware of the risks related to inactivity. Just over half (52%), however, said that they were aware of the risks related to radiotherapy. Nevertheless, 75% of participants knew about the risks relating to cancer surgery and chemotherapy. “To all intents and purposes, all types of cancer drug can significantly affect the risk of developing a clot. And this is also the case for more modern types of treatment, such as immunotherapy,” said Dr. Falanga.

Most respondents reported that they got information about cancer-associated thrombosis verbally, usually from their hospital doctor (11%). Some respondents (6%) said that they found out about it from their own research, usually online. Almost 1 in 4 patients (24%) in Italy said that they first became aware of CAT when they suffered a blood clot. Answers to questions about knowledge of symptoms show that 58% of Italian patients and caregivers know that swelling of the lower limbs can be a symptom of DVT, and the same percentage knows that shortness of breath might indicate PE.

In terms of preventive action, the picture in Italy is somewhat variable: 74% of participants were aware of the importance of walking, but far fewer knew about the need to stop smoking (57%) and stretch the legs (35%). Of the 41% of Italians who were also taking an anticoagulant drug, 53% said that they knew about the possible side effects of such medication.
 

Which way forward?

“The high rate of CAT suggests that, despite the clinical evidence and clear guideline recommendations for patients with cancer, CAT prevention and recognition remain low among healthcare professionals,” the authors write.

The results of the ECPC survey further confirm those of previous studies, highlighting patients’ lack of knowledge about CAT and the need for more in-depth discussions between physician and patient.

So, what can be done? As highlighted by previous studies, “patients’ experiences are an education in themselves, particularly for the oncology care team,” the authors write. “Once the patient has a thrombosis, the opportunity for thrombosis prevention, which should be the most crucial focus of the care clinics (surgical, oncology, and palliative care), is gone,” they add.

“Oncology professionals, as well as other members of the patient’s care team (eg, internists, surgeons, nurses), need to perform better, at every stage of the patient’s cancer pathway, to ensure patients are aware of CAT and their individual risk to develop a blood clot,” said Dr. Falanga. She explained that in this group, it is the general practitioner who is the first contact. “These professionals are on the front line of the battle; they are among the first healthcare workers given the chance to suspect a clot and should, therefore, be fully aware of the increased risk in oncology patients,” she reiterated.

Experts agree on the fact that a multidisciplinary approach is of utmost importance in this context: the different roles in the team must be clear. “It is also fundamental to establish who does what in terms of educating and informing the patient,” said Dr. Falanga.

The researchers also put forward an example of a successful initiative: the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTE-PACC) program. The initiative was developed by experts from the University of Vermont and was described in a recent article in JCO Oncology Practice.

Numerous resources are available online to help physicians talk to their patients and explain the risks linked to CAT along the continuum of cancer care. Among them is a resource titled, “Cancer Associated Thrombosis (CAT): Be Clot Conscious,” which can be found on the ECPC’s website.

“We have a collective responsibility using the ECPC patient survey as a baseline to inform patients with cancer on how to identify signs and symptoms of CAT to enable faster diagnosis and treatment,” the authors conclude.

This article was translated from Univadis Italy.

More than 70% of cancer patients do not know that they are at greater risk of deep vein thrombosis (DVT) than the general population. It is up to their physician to discuss this with them.

This link is explained by the authors of an article in Cancer Treatment and Research Communications that reports results of a survey carried out by the European Cancer Patient Coalition (ECPC). “The aim of this pan-European patient survey was to assess patient awareness and knowledge about cancer-associated thrombosis (CAT), including risk factors, signs and symptoms, and interventions, to better prevent and treat CAT,” write the authors. “The idea was to create a sort of starting point for subsequent communication and information strategies and for comparing the results of any action taken in this area,” they add.

A roundtable discussion that included oncology healthcare professionals, policymakers, and patient advocates was convened to discuss and review the evidence regarding their ongoing concerns of excessive CAT-associated morbidity and mortality, as well as patients’ desire for greater CAT awareness.

“These discussions demonstrated that very little change had occurred over the years and that greater knowledge about CAT was still needed across the spectrum of healthcare practitioners and patients, particularly regarding primary and secondary prevention of thrombosis,” the authors write.

It was from this starting point that the idea for the pan-European survey was born. The ECPC, widely viewed as the “unified voice of cancer patients across Europe,” led the survey. This survey spanned six countries (France, Germany, Greece, Italy, United Kingdom, and Spain) and involved 1,365 patients and caregivers. The ECPC survey result was originally released at World Thrombosis Day in late 2018.

In an interview, Anna Falanga, MD, the main author of the article and professor of hematology at the University of Milan-Bicocca, Italy, reviewed the results and explained how to improve knowledge of CAT among patients with cancer.

“Data support that up to 20% of patients with cancer will experience venous thromboembolism (VTE), which is approximately 4–5 times higher than the general population,” said Dr. Falanga, who is also chief of the department of immunohematology and transfusion medicine and the Thrombosis and Hemostasis Center at the Hospital Papa Giovanni XXIII, in Bergamo, Italy.

“We have known about the link between thrombosis and cancer since the 19th century, but it has taken until midway through the last century for our level of understanding and awareness of the problem to reach its current level. Initially, this was limited to fundamental research, with large advances in our understanding of the mechanisms of the link between the two; it has only been more recently that we have had clinical studies that have piqued the interest of healthcare professionals, who were previously uninterested in the topic,” she said.
 

Poor understanding

One piece of data stands out from the European survey: Nearly three quarters of respondents (72%) said that before taking part in the survey, they were not aware that people with cancer have a higher-than-normal risk of developing thrombosis. “We asked participants to rate their overall understanding of CAT on a scale of 1 (low) to 10 (high), with the average (mean) score obtained being 4.1. Only 21% of patients gave a rating of 7 or above (high understanding). The average rating was very similar in the different countries surveyed,” write the authors. They note that the survey also assessed how much participants had learned about the topic from their physicians.

Approximately 35% of patients were made aware of CAT either immediately before or at the time of their cancer diagnosis. Of particular concern, one quarter (26%) of respondents (the largest proportion) noted that they first became aware of CAT when they suffered a blood clot. The average rating was very similar in the different countries surveyed. “Let us not forget that cancer and cancer treatments themselves cause a number of side effects, some of which can be very serious, so in some ways, a clot might be seen as a minor problem. Yet, in reality, it isn’t. It is a significant cause of death and disease in cancer patients,” said Dr. Falanga.

When discussing prevention, most respondents (87%) said they were aware that taking a walk could reduce their risk. Slightly fewer were aware that stopping smoking could reduce their risk (75%), and even fewer were aware that keeping hydrated (63%) and stretching their legs (55%) could reduce their risk.

Symptoms of CAT appeared to be relatively well known; 73% of survey participants indicated that they were aware that swelling in the foot, ankle, or leg could be a sign of DVT, and 71% indicated that shortness of breath could be a sign of pulmonary embolism (PE). “Other symptoms, however, were less well known, with just over half (57%) of participants being aware that pain, cramping, and tenderness could be a sign of DVT. About one third (33%) knew that irregular heartbeat could be a sign of PE. These results varied between countries,” according to the authors.

The survey highlighted that just over a third of respondents said that they were currently using anticoagulants, although almost all (96%) knew that anticoagulants could be used to effectively treat thrombosis. Only 41% of those using anticoagulants said they had been told about any possible side effects.
 

The Italian situation

The report containing the full results of the European survey goes even further, since, in addition to its overall results, it also gives information about individual countries.

The data from Italy, which are based on 246 persons, show that only 27% of patients and caregivers were aware of the increased risk of thrombosis after a cancer diagnosis. This figure is in line with the overall results of the survey, although the average score of the 10-point scale was lower for the Italy cohort (3.3/10 vs 4.1/10).

The results are more variable in terms of knowledge of risk factors. Most respondents (89%) said that they were aware of the risks related to inactivity. Just over half (52%), however, said that they were aware of the risks related to radiotherapy. Nevertheless, 75% of participants knew about the risks relating to cancer surgery and chemotherapy. “To all intents and purposes, all types of cancer drug can significantly affect the risk of developing a clot. And this is also the case for more modern types of treatment, such as immunotherapy,” said Dr. Falanga.

Most respondents reported that they got information about cancer-associated thrombosis verbally, usually from their hospital doctor (11%). Some respondents (6%) said that they found out about it from their own research, usually online. Almost 1 in 4 patients (24%) in Italy said that they first became aware of CAT when they suffered a blood clot. Answers to questions about knowledge of symptoms show that 58% of Italian patients and caregivers know that swelling of the lower limbs can be a symptom of DVT, and the same percentage knows that shortness of breath might indicate PE.

In terms of preventive action, the picture in Italy is somewhat variable: 74% of participants were aware of the importance of walking, but far fewer knew about the need to stop smoking (57%) and stretch the legs (35%). Of the 41% of Italians who were also taking an anticoagulant drug, 53% said that they knew about the possible side effects of such medication.
 

Which way forward?

“The high rate of CAT suggests that, despite the clinical evidence and clear guideline recommendations for patients with cancer, CAT prevention and recognition remain low among healthcare professionals,” the authors write.

The results of the ECPC survey further confirm those of previous studies, highlighting patients’ lack of knowledge about CAT and the need for more in-depth discussions between physician and patient.

So, what can be done? As highlighted by previous studies, “patients’ experiences are an education in themselves, particularly for the oncology care team,” the authors write. “Once the patient has a thrombosis, the opportunity for thrombosis prevention, which should be the most crucial focus of the care clinics (surgical, oncology, and palliative care), is gone,” they add.

“Oncology professionals, as well as other members of the patient’s care team (eg, internists, surgeons, nurses), need to perform better, at every stage of the patient’s cancer pathway, to ensure patients are aware of CAT and their individual risk to develop a blood clot,” said Dr. Falanga. She explained that in this group, it is the general practitioner who is the first contact. “These professionals are on the front line of the battle; they are among the first healthcare workers given the chance to suspect a clot and should, therefore, be fully aware of the increased risk in oncology patients,” she reiterated.

Experts agree on the fact that a multidisciplinary approach is of utmost importance in this context: the different roles in the team must be clear. “It is also fundamental to establish who does what in terms of educating and informing the patient,” said Dr. Falanga.

The researchers also put forward an example of a successful initiative: the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTE-PACC) program. The initiative was developed by experts from the University of Vermont and was described in a recent article in JCO Oncology Practice.

Numerous resources are available online to help physicians talk to their patients and explain the risks linked to CAT along the continuum of cancer care. Among them is a resource titled, “Cancer Associated Thrombosis (CAT): Be Clot Conscious,” which can be found on the ECPC’s website.

“We have a collective responsibility using the ECPC patient survey as a baseline to inform patients with cancer on how to identify signs and symptoms of CAT to enable faster diagnosis and treatment,” the authors conclude.

This article was translated from Univadis Italy.

More than 70% of cancer patients do not know that they are at greater risk of deep vein thrombosis (DVT) than the general population. It is up to their physician to discuss this with them.

This link is explained by the authors of an article in Cancer Treatment and Research Communications that reports results of a survey carried out by the European Cancer Patient Coalition (ECPC). “The aim of this pan-European patient survey was to assess patient awareness and knowledge about cancer-associated thrombosis (CAT), including risk factors, signs and symptoms, and interventions, to better prevent and treat CAT,” write the authors. “The idea was to create a sort of starting point for subsequent communication and information strategies and for comparing the results of any action taken in this area,” they add.

A roundtable discussion that included oncology healthcare professionals, policymakers, and patient advocates was convened to discuss and review the evidence regarding their ongoing concerns of excessive CAT-associated morbidity and mortality, as well as patients’ desire for greater CAT awareness.

“These discussions demonstrated that very little change had occurred over the years and that greater knowledge about CAT was still needed across the spectrum of healthcare practitioners and patients, particularly regarding primary and secondary prevention of thrombosis,” the authors write.

It was from this starting point that the idea for the pan-European survey was born. The ECPC, widely viewed as the “unified voice of cancer patients across Europe,” led the survey. This survey spanned six countries (France, Germany, Greece, Italy, United Kingdom, and Spain) and involved 1,365 patients and caregivers. The ECPC survey result was originally released at World Thrombosis Day in late 2018.

In an interview, Anna Falanga, MD, the main author of the article and professor of hematology at the University of Milan-Bicocca, Italy, reviewed the results and explained how to improve knowledge of CAT among patients with cancer.

“Data support that up to 20% of patients with cancer will experience venous thromboembolism (VTE), which is approximately 4–5 times higher than the general population,” said Dr. Falanga, who is also chief of the department of immunohematology and transfusion medicine and the Thrombosis and Hemostasis Center at the Hospital Papa Giovanni XXIII, in Bergamo, Italy.

“We have known about the link between thrombosis and cancer since the 19th century, but it has taken until midway through the last century for our level of understanding and awareness of the problem to reach its current level. Initially, this was limited to fundamental research, with large advances in our understanding of the mechanisms of the link between the two; it has only been more recently that we have had clinical studies that have piqued the interest of healthcare professionals, who were previously uninterested in the topic,” she said.
 

Poor understanding

One piece of data stands out from the European survey: Nearly three quarters of respondents (72%) said that before taking part in the survey, they were not aware that people with cancer have a higher-than-normal risk of developing thrombosis. “We asked participants to rate their overall understanding of CAT on a scale of 1 (low) to 10 (high), with the average (mean) score obtained being 4.1. Only 21% of patients gave a rating of 7 or above (high understanding). The average rating was very similar in the different countries surveyed,” write the authors. They note that the survey also assessed how much participants had learned about the topic from their physicians.

Approximately 35% of patients were made aware of CAT either immediately before or at the time of their cancer diagnosis. Of particular concern, one quarter (26%) of respondents (the largest proportion) noted that they first became aware of CAT when they suffered a blood clot. The average rating was very similar in the different countries surveyed. “Let us not forget that cancer and cancer treatments themselves cause a number of side effects, some of which can be very serious, so in some ways, a clot might be seen as a minor problem. Yet, in reality, it isn’t. It is a significant cause of death and disease in cancer patients,” said Dr. Falanga.

When discussing prevention, most respondents (87%) said they were aware that taking a walk could reduce their risk. Slightly fewer were aware that stopping smoking could reduce their risk (75%), and even fewer were aware that keeping hydrated (63%) and stretching their legs (55%) could reduce their risk.

Symptoms of CAT appeared to be relatively well known; 73% of survey participants indicated that they were aware that swelling in the foot, ankle, or leg could be a sign of DVT, and 71% indicated that shortness of breath could be a sign of pulmonary embolism (PE). “Other symptoms, however, were less well known, with just over half (57%) of participants being aware that pain, cramping, and tenderness could be a sign of DVT. About one third (33%) knew that irregular heartbeat could be a sign of PE. These results varied between countries,” according to the authors.

The survey highlighted that just over a third of respondents said that they were currently using anticoagulants, although almost all (96%) knew that anticoagulants could be used to effectively treat thrombosis. Only 41% of those using anticoagulants said they had been told about any possible side effects.
 

The Italian situation

The report containing the full results of the European survey goes even further, since, in addition to its overall results, it also gives information about individual countries.

The data from Italy, which are based on 246 persons, show that only 27% of patients and caregivers were aware of the increased risk of thrombosis after a cancer diagnosis. This figure is in line with the overall results of the survey, although the average score of the 10-point scale was lower for the Italy cohort (3.3/10 vs 4.1/10).

The results are more variable in terms of knowledge of risk factors. Most respondents (89%) said that they were aware of the risks related to inactivity. Just over half (52%), however, said that they were aware of the risks related to radiotherapy. Nevertheless, 75% of participants knew about the risks relating to cancer surgery and chemotherapy. “To all intents and purposes, all types of cancer drug can significantly affect the risk of developing a clot. And this is also the case for more modern types of treatment, such as immunotherapy,” said Dr. Falanga.

Most respondents reported that they got information about cancer-associated thrombosis verbally, usually from their hospital doctor (11%). Some respondents (6%) said that they found out about it from their own research, usually online. Almost 1 in 4 patients (24%) in Italy said that they first became aware of CAT when they suffered a blood clot. Answers to questions about knowledge of symptoms show that 58% of Italian patients and caregivers know that swelling of the lower limbs can be a symptom of DVT, and the same percentage knows that shortness of breath might indicate PE.

In terms of preventive action, the picture in Italy is somewhat variable: 74% of participants were aware of the importance of walking, but far fewer knew about the need to stop smoking (57%) and stretch the legs (35%). Of the 41% of Italians who were also taking an anticoagulant drug, 53% said that they knew about the possible side effects of such medication.
 

Which way forward?

“The high rate of CAT suggests that, despite the clinical evidence and clear guideline recommendations for patients with cancer, CAT prevention and recognition remain low among healthcare professionals,” the authors write.

The results of the ECPC survey further confirm those of previous studies, highlighting patients’ lack of knowledge about CAT and the need for more in-depth discussions between physician and patient.

So, what can be done? As highlighted by previous studies, “patients’ experiences are an education in themselves, particularly for the oncology care team,” the authors write. “Once the patient has a thrombosis, the opportunity for thrombosis prevention, which should be the most crucial focus of the care clinics (surgical, oncology, and palliative care), is gone,” they add.

“Oncology professionals, as well as other members of the patient’s care team (eg, internists, surgeons, nurses), need to perform better, at every stage of the patient’s cancer pathway, to ensure patients are aware of CAT and their individual risk to develop a blood clot,” said Dr. Falanga. She explained that in this group, it is the general practitioner who is the first contact. “These professionals are on the front line of the battle; they are among the first healthcare workers given the chance to suspect a clot and should, therefore, be fully aware of the increased risk in oncology patients,” she reiterated.

Experts agree on the fact that a multidisciplinary approach is of utmost importance in this context: the different roles in the team must be clear. “It is also fundamental to establish who does what in terms of educating and informing the patient,” said Dr. Falanga.

The researchers also put forward an example of a successful initiative: the Venous Thromboembolism Prevention in the Ambulatory Cancer Clinic (VTE-PACC) program. The initiative was developed by experts from the University of Vermont and was described in a recent article in JCO Oncology Practice.

Numerous resources are available online to help physicians talk to their patients and explain the risks linked to CAT along the continuum of cancer care. Among them is a resource titled, “Cancer Associated Thrombosis (CAT): Be Clot Conscious,” which can be found on the ECPC’s website.

“We have a collective responsibility using the ECPC patient survey as a baseline to inform patients with cancer on how to identify signs and symptoms of CAT to enable faster diagnosis and treatment,” the authors conclude.

This article was translated from Univadis Italy.

Young stroke patients have an increased risk of being diagnosed with a new cancer in the years following their stroke, a new study shows, raising the possibility that the stroke might be the first manifestation of an underlying cancer.

The data were presented by Jamie Verhoeven, MD, Radboud University Medical Centre, the Netherlands, at the recent European Stroke Organisation Conference 2022.

Dr. Verhoeven noted that 10% of all stroke cases occur in individuals younger than 50 years. During the past few decades, the incidence of stroke in the young has steadily increased, whereas the incidence of stroke in older adults has stabilized or decreased.

“Stroke in the young differs from stroke in older patients, and one of the major differences is that stroke in the young has a higher proportion of cryptogenic stroke, with no clear cause found in over one-third of patients,” she said.

Also, having an active cancer is known to be a risk factor for thrombosis. This association is strongest in venous thrombosis and has been less well investigated in arterial thrombosis, Dr. Verhoeven reported.

Her group aimed to investigate whether in some patients with cryptogenic stroke, this may be the first manifestation of an underlying cancer. “If this hypothesis is true, then it would be more obvious in young patients who have a higher incidence of cryptogenic stroke,” she said.

They performed a population-based observational cohort study using diagnostic ICD codes from the national Hospital Discharge Registry in the Netherlands and the Dutch Population Registry from 1998 to 2019.

Patients with a history of cancer before their first stroke and those with central nervous system cancers at the time of stroke or nonmelanoma skin cancers (which have been shown to have no systemic effects) were excluded.

Reference data came from the Netherlands Comprehensive Cancer Organisation, which collects data on all cancer diagnoses in the country.

The researchers identified 27,616 young stroke patients (age range, 15-49 years; median age, 45 years) and 362,782 older stroke patients (age range, 50 years and older; median age, 76 years).

The cumulative incidence of any cancer at 10 years was 3.7% in the younger group and 8.5% in the older group.

The data were compared with matched peers from the general population. The main outcome measures were cumulative incidence of first-ever cancer after stroke (stratified by stroke subtype, age and sex) and standardized incidence rates.

Results showed that the risk for cancer was higher in the younger age group than in the matched general population.

In this age group, the 1-year risk of any new cancer was 2.6 times higher (95% confidence interval, 2.2-3.1) after ischemic stroke and 5.4 times (95% CI, 3.8-7.3) after intracerebral hemorrhage than in matched peers from the general population.

In contrast, in stroke patients older than 50 years, the 1-year risk for any new cancer was 1.2 times higher than the general population after either ischemic or hemorrhagic stroke.

“The younger patients have a higher risk increase of cancer than older patients, and this risk increase is most evident in the first 1 to 2 years after stroke but remains statistically significant for up to 5 to 8 years later,” Dr. Verhoeven said.

The cancers that were most involved in this risk increase were those of the lower respiratory tract, hematologic cancers, and gastrointestinal cancers.

The main strength of this study was the use of national databases that allowed for a very large sample size, but this brings with it the danger of misclassification of events and the lack of clinical data, Dr. Verhoeven noted.

“Young stroke patients are at increased risk of developing a new cancer in the years following their stroke compared to peers from the general population, but this risk is only marginally increased in the older stroke population,” she concluded.

She pointed out that it is not possible to confirm any causal relation from this study design, but a clear association has been shown.

“We need more studies into this field. We need a large clinical dataset to examine which clinical phenotypes are associated with possible underlying cancers to identify which patients are most at risk. We are already working on this,” she said. “Then it remains to be investigated whether screening for an underlying cancer should be added to the diagnostic workup in young stroke patients.”

Commenting on the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh, Scotland, and a consultant neurologist in NHS Lothian, said it was difficult to know whether the link shown between stroke and cancer was causal, but the effect size in this study was “quite large.”

He pointed out that the associations with bowel and lung cancer could be due to shared risk factors, such as smoking, but he said the finding on a link with hematologic cancers is “interesting.”

Noting that there are links between hematologic cancers and thrombotic events, he said: “People have wondered if that is because of clonal expansion, which has been shown to increase the risk of atherosclerosis, so the question is whether this is some kind of common risk factor here.”

Dr. Verhoeven said she did not believe that shared risk factors fully explained the difference in increased risks between young and older patients.

“It does not fully explain why the risk of cancer is specifically higher in the first 1 to 2 years after the stroke diagnosis. I would think if it was just shared risk factors, the risk increase should remain relatively stable, or even increase due to the build-up of exposure to risk factors over the years,” she said.

Dr. Whiteley said that data like these are “really useful in trying to estimate these associations and it gives us some hypotheses to investigate in smaller mechanistic studies.”

Asked whether these data justify screening younger cryptogenic stroke patients more systematically for cancer, Dr. Whiteley replied: “I think we need some absolute risk estimates for that; for example, what proportion of younger patients would be at risk over the next few years when that screening would make a difference.”

Dr. Verhoeven reports no disclosures.

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

Young stroke patients have an increased risk of being diagnosed with a new cancer in the years following their stroke, a new study shows, raising the possibility that the stroke might be the first manifestation of an underlying cancer.

The data were presented by Jamie Verhoeven, MD, Radboud University Medical Centre, the Netherlands, at the recent European Stroke Organisation Conference 2022.

Dr. Verhoeven noted that 10% of all stroke cases occur in individuals younger than 50 years. During the past few decades, the incidence of stroke in the young has steadily increased, whereas the incidence of stroke in older adults has stabilized or decreased.

“Stroke in the young differs from stroke in older patients, and one of the major differences is that stroke in the young has a higher proportion of cryptogenic stroke, with no clear cause found in over one-third of patients,” she said.

Also, having an active cancer is known to be a risk factor for thrombosis. This association is strongest in venous thrombosis and has been less well investigated in arterial thrombosis, Dr. Verhoeven reported.

Her group aimed to investigate whether in some patients with cryptogenic stroke, this may be the first manifestation of an underlying cancer. “If this hypothesis is true, then it would be more obvious in young patients who have a higher incidence of cryptogenic stroke,” she said.

They performed a population-based observational cohort study using diagnostic ICD codes from the national Hospital Discharge Registry in the Netherlands and the Dutch Population Registry from 1998 to 2019.

Patients with a history of cancer before their first stroke and those with central nervous system cancers at the time of stroke or nonmelanoma skin cancers (which have been shown to have no systemic effects) were excluded.

Reference data came from the Netherlands Comprehensive Cancer Organisation, which collects data on all cancer diagnoses in the country.

The researchers identified 27,616 young stroke patients (age range, 15-49 years; median age, 45 years) and 362,782 older stroke patients (age range, 50 years and older; median age, 76 years).

The cumulative incidence of any cancer at 10 years was 3.7% in the younger group and 8.5% in the older group.

The data were compared with matched peers from the general population. The main outcome measures were cumulative incidence of first-ever cancer after stroke (stratified by stroke subtype, age and sex) and standardized incidence rates.

Results showed that the risk for cancer was higher in the younger age group than in the matched general population.

In this age group, the 1-year risk of any new cancer was 2.6 times higher (95% confidence interval, 2.2-3.1) after ischemic stroke and 5.4 times (95% CI, 3.8-7.3) after intracerebral hemorrhage than in matched peers from the general population.

In contrast, in stroke patients older than 50 years, the 1-year risk for any new cancer was 1.2 times higher than the general population after either ischemic or hemorrhagic stroke.

“The younger patients have a higher risk increase of cancer than older patients, and this risk increase is most evident in the first 1 to 2 years after stroke but remains statistically significant for up to 5 to 8 years later,” Dr. Verhoeven said.

The cancers that were most involved in this risk increase were those of the lower respiratory tract, hematologic cancers, and gastrointestinal cancers.

The main strength of this study was the use of national databases that allowed for a very large sample size, but this brings with it the danger of misclassification of events and the lack of clinical data, Dr. Verhoeven noted.

“Young stroke patients are at increased risk of developing a new cancer in the years following their stroke compared to peers from the general population, but this risk is only marginally increased in the older stroke population,” she concluded.

She pointed out that it is not possible to confirm any causal relation from this study design, but a clear association has been shown.

“We need more studies into this field. We need a large clinical dataset to examine which clinical phenotypes are associated with possible underlying cancers to identify which patients are most at risk. We are already working on this,” she said. “Then it remains to be investigated whether screening for an underlying cancer should be added to the diagnostic workup in young stroke patients.”

Commenting on the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh, Scotland, and a consultant neurologist in NHS Lothian, said it was difficult to know whether the link shown between stroke and cancer was causal, but the effect size in this study was “quite large.”

He pointed out that the associations with bowel and lung cancer could be due to shared risk factors, such as smoking, but he said the finding on a link with hematologic cancers is “interesting.”

Noting that there are links between hematologic cancers and thrombotic events, he said: “People have wondered if that is because of clonal expansion, which has been shown to increase the risk of atherosclerosis, so the question is whether this is some kind of common risk factor here.”

Dr. Verhoeven said she did not believe that shared risk factors fully explained the difference in increased risks between young and older patients.

“It does not fully explain why the risk of cancer is specifically higher in the first 1 to 2 years after the stroke diagnosis. I would think if it was just shared risk factors, the risk increase should remain relatively stable, or even increase due to the build-up of exposure to risk factors over the years,” she said.

Dr. Whiteley said that data like these are “really useful in trying to estimate these associations and it gives us some hypotheses to investigate in smaller mechanistic studies.”

Asked whether these data justify screening younger cryptogenic stroke patients more systematically for cancer, Dr. Whiteley replied: “I think we need some absolute risk estimates for that; for example, what proportion of younger patients would be at risk over the next few years when that screening would make a difference.”

Dr. Verhoeven reports no disclosures.

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

Young stroke patients have an increased risk of being diagnosed with a new cancer in the years following their stroke, a new study shows, raising the possibility that the stroke might be the first manifestation of an underlying cancer.

The data were presented by Jamie Verhoeven, MD, Radboud University Medical Centre, the Netherlands, at the recent European Stroke Organisation Conference 2022.

Dr. Verhoeven noted that 10% of all stroke cases occur in individuals younger than 50 years. During the past few decades, the incidence of stroke in the young has steadily increased, whereas the incidence of stroke in older adults has stabilized or decreased.

“Stroke in the young differs from stroke in older patients, and one of the major differences is that stroke in the young has a higher proportion of cryptogenic stroke, with no clear cause found in over one-third of patients,” she said.

Also, having an active cancer is known to be a risk factor for thrombosis. This association is strongest in venous thrombosis and has been less well investigated in arterial thrombosis, Dr. Verhoeven reported.

Her group aimed to investigate whether in some patients with cryptogenic stroke, this may be the first manifestation of an underlying cancer. “If this hypothesis is true, then it would be more obvious in young patients who have a higher incidence of cryptogenic stroke,” she said.

They performed a population-based observational cohort study using diagnostic ICD codes from the national Hospital Discharge Registry in the Netherlands and the Dutch Population Registry from 1998 to 2019.

Patients with a history of cancer before their first stroke and those with central nervous system cancers at the time of stroke or nonmelanoma skin cancers (which have been shown to have no systemic effects) were excluded.

Reference data came from the Netherlands Comprehensive Cancer Organisation, which collects data on all cancer diagnoses in the country.

The researchers identified 27,616 young stroke patients (age range, 15-49 years; median age, 45 years) and 362,782 older stroke patients (age range, 50 years and older; median age, 76 years).

The cumulative incidence of any cancer at 10 years was 3.7% in the younger group and 8.5% in the older group.

The data were compared with matched peers from the general population. The main outcome measures were cumulative incidence of first-ever cancer after stroke (stratified by stroke subtype, age and sex) and standardized incidence rates.

Results showed that the risk for cancer was higher in the younger age group than in the matched general population.

In this age group, the 1-year risk of any new cancer was 2.6 times higher (95% confidence interval, 2.2-3.1) after ischemic stroke and 5.4 times (95% CI, 3.8-7.3) after intracerebral hemorrhage than in matched peers from the general population.

In contrast, in stroke patients older than 50 years, the 1-year risk for any new cancer was 1.2 times higher than the general population after either ischemic or hemorrhagic stroke.

“The younger patients have a higher risk increase of cancer than older patients, and this risk increase is most evident in the first 1 to 2 years after stroke but remains statistically significant for up to 5 to 8 years later,” Dr. Verhoeven said.

The cancers that were most involved in this risk increase were those of the lower respiratory tract, hematologic cancers, and gastrointestinal cancers.

The main strength of this study was the use of national databases that allowed for a very large sample size, but this brings with it the danger of misclassification of events and the lack of clinical data, Dr. Verhoeven noted.

“Young stroke patients are at increased risk of developing a new cancer in the years following their stroke compared to peers from the general population, but this risk is only marginally increased in the older stroke population,” she concluded.

She pointed out that it is not possible to confirm any causal relation from this study design, but a clear association has been shown.

“We need more studies into this field. We need a large clinical dataset to examine which clinical phenotypes are associated with possible underlying cancers to identify which patients are most at risk. We are already working on this,” she said. “Then it remains to be investigated whether screening for an underlying cancer should be added to the diagnostic workup in young stroke patients.”

Commenting on the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh, Scotland, and a consultant neurologist in NHS Lothian, said it was difficult to know whether the link shown between stroke and cancer was causal, but the effect size in this study was “quite large.”

He pointed out that the associations with bowel and lung cancer could be due to shared risk factors, such as smoking, but he said the finding on a link with hematologic cancers is “interesting.”

Noting that there are links between hematologic cancers and thrombotic events, he said: “People have wondered if that is because of clonal expansion, which has been shown to increase the risk of atherosclerosis, so the question is whether this is some kind of common risk factor here.”

Dr. Verhoeven said she did not believe that shared risk factors fully explained the difference in increased risks between young and older patients.

“It does not fully explain why the risk of cancer is specifically higher in the first 1 to 2 years after the stroke diagnosis. I would think if it was just shared risk factors, the risk increase should remain relatively stable, or even increase due to the build-up of exposure to risk factors over the years,” she said.

Dr. Whiteley said that data like these are “really useful in trying to estimate these associations and it gives us some hypotheses to investigate in smaller mechanistic studies.”

Asked whether these data justify screening younger cryptogenic stroke patients more systematically for cancer, Dr. Whiteley replied: “I think we need some absolute risk estimates for that; for example, what proportion of younger patients would be at risk over the next few years when that screening would make a difference.”

Dr. Verhoeven reports no disclosures.

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

The benefit of endovascular therapy in the treatment of stroke caused by an occlusion of the basilar artery has finally been confirmed in the ATTENTION randomized trial.

The study, conducted in China, showed that endovascular therapy for basilar artery occlusion is associated with higher rates of favorable and independent outcomes, as well as lower overall disability and lower mortality at 90 days, than best medical management alone.

The results were presented by Raul Nogueira, MD, professor of neurology at the University of Pittsburgh School of Medicine, at the European Stroke Organisation Conference (ESOC) 2022, where they were greeted with applause from the audience.

The number needed to treat was just four.

“There were no surprises with secondary endpoints; everything was highly statistically significant,” Dr. Nogueira said.

Specifically, there was a lower rate of overall disability in the shift analysis, with a common odds ratio of 2.8 favoring the intervention.  

Safety results showed an increased risk for symptomatic ICH in the endovascular group (5.3% vs. 0.0%) but, despite that, 90-day mortality was significantly lower in the endovascular group (36.7% vs. 55.3%).

Dr. Nogueira noted a limitation of the study was that it was conducted in China.

“This was a Chinese study and, as Asians are known to have higher rates of intracranial atherosclerotic disease, the overall degree of generalizability of our findings to Western countries needs to be considered,” he commented.

However, subgroup analysis showed no treatment effect modification based on the presence of intracranial atherosclerotic disease, he noted.

Also, the proportion of comorbidities in the ATTENTION trial was similar to that in the BASICS trial, with the same degree of diabetes and atrial fibrillation.

Dr. Nogueira concluded that, in contrast to previous randomized trials of endovascular treatment for basilar artery occlusion, the ATTENTION trial was able to reinforce consecutive enrollment, resulting in a fast recruitment while minimizing crossovers. 

Furthermore, he pointed out that the overall results are consistent with modern era observational studies, large registries, and meta-analysis.

Commenting on the study, Joanna Wardlaw, MD, professor of applied neuroimaging at the University of Edinburgh (Scotland), and chair of the ESOC Planning Group, said: “This is a very important result, since it provides confirmation beyond doubt the benefit of thrombectomy versus medical therapy for basilar artery occlusion stroke up to 12 hours after onset.”

Dr. Wardlaw added: “The trial was large enough to provide clear results and to enable subgroup analyses; no subgroup did not benefit from thrombectomy.”

In a discussion after the presentation, Urs Fischer, MD, chair of the department of neurology at the University Hospital Basel, Switzerland, said he was not surprised by the results of the ATTENTION trial.

“We have been doing thrombectomy in patients with basilar artery occlusion now for 20 years, although trials are extremely important to answer these questions, so now we have some clear evidence,” Dr. Fischer said. “Nevertheless, there are some caveats, as this is an Asian population, but this is a proof of concept, and it is going in the right direction.”

The ATTENTION trial was sponsored by the First Affiliated Hospital of University of Science and Technology of China.

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

The benefit of endovascular therapy in the treatment of stroke caused by an occlusion of the basilar artery has finally been confirmed in the ATTENTION randomized trial.

The study, conducted in China, showed that endovascular therapy for basilar artery occlusion is associated with higher rates of favorable and independent outcomes, as well as lower overall disability and lower mortality at 90 days, than best medical management alone.

The results were presented by Raul Nogueira, MD, professor of neurology at the University of Pittsburgh School of Medicine, at the European Stroke Organisation Conference (ESOC) 2022, where they were greeted with applause from the audience.

The number needed to treat was just four.

“There were no surprises with secondary endpoints; everything was highly statistically significant,” Dr. Nogueira said.

Specifically, there was a lower rate of overall disability in the shift analysis, with a common odds ratio of 2.8 favoring the intervention.  

Safety results showed an increased risk for symptomatic ICH in the endovascular group (5.3% vs. 0.0%) but, despite that, 90-day mortality was significantly lower in the endovascular group (36.7% vs. 55.3%).

Dr. Nogueira noted a limitation of the study was that it was conducted in China.

“This was a Chinese study and, as Asians are known to have higher rates of intracranial atherosclerotic disease, the overall degree of generalizability of our findings to Western countries needs to be considered,” he commented.

However, subgroup analysis showed no treatment effect modification based on the presence of intracranial atherosclerotic disease, he noted.

Also, the proportion of comorbidities in the ATTENTION trial was similar to that in the BASICS trial, with the same degree of diabetes and atrial fibrillation.

Dr. Nogueira concluded that, in contrast to previous randomized trials of endovascular treatment for basilar artery occlusion, the ATTENTION trial was able to reinforce consecutive enrollment, resulting in a fast recruitment while minimizing crossovers. 

Furthermore, he pointed out that the overall results are consistent with modern era observational studies, large registries, and meta-analysis.

Commenting on the study, Joanna Wardlaw, MD, professor of applied neuroimaging at the University of Edinburgh (Scotland), and chair of the ESOC Planning Group, said: “This is a very important result, since it provides confirmation beyond doubt the benefit of thrombectomy versus medical therapy for basilar artery occlusion stroke up to 12 hours after onset.”

Dr. Wardlaw added: “The trial was large enough to provide clear results and to enable subgroup analyses; no subgroup did not benefit from thrombectomy.”

In a discussion after the presentation, Urs Fischer, MD, chair of the department of neurology at the University Hospital Basel, Switzerland, said he was not surprised by the results of the ATTENTION trial.

“We have been doing thrombectomy in patients with basilar artery occlusion now for 20 years, although trials are extremely important to answer these questions, so now we have some clear evidence,” Dr. Fischer said. “Nevertheless, there are some caveats, as this is an Asian population, but this is a proof of concept, and it is going in the right direction.”

The ATTENTION trial was sponsored by the First Affiliated Hospital of University of Science and Technology of China.

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

The benefit of endovascular therapy in the treatment of stroke caused by an occlusion of the basilar artery has finally been confirmed in the ATTENTION randomized trial.

The study, conducted in China, showed that endovascular therapy for basilar artery occlusion is associated with higher rates of favorable and independent outcomes, as well as lower overall disability and lower mortality at 90 days, than best medical management alone.

The results were presented by Raul Nogueira, MD, professor of neurology at the University of Pittsburgh School of Medicine, at the European Stroke Organisation Conference (ESOC) 2022, where they were greeted with applause from the audience.

The number needed to treat was just four.

“There were no surprises with secondary endpoints; everything was highly statistically significant,” Dr. Nogueira said.

Specifically, there was a lower rate of overall disability in the shift analysis, with a common odds ratio of 2.8 favoring the intervention.  

Safety results showed an increased risk for symptomatic ICH in the endovascular group (5.3% vs. 0.0%) but, despite that, 90-day mortality was significantly lower in the endovascular group (36.7% vs. 55.3%).

Dr. Nogueira noted a limitation of the study was that it was conducted in China.

“This was a Chinese study and, as Asians are known to have higher rates of intracranial atherosclerotic disease, the overall degree of generalizability of our findings to Western countries needs to be considered,” he commented.

However, subgroup analysis showed no treatment effect modification based on the presence of intracranial atherosclerotic disease, he noted.

Also, the proportion of comorbidities in the ATTENTION trial was similar to that in the BASICS trial, with the same degree of diabetes and atrial fibrillation.

Dr. Nogueira concluded that, in contrast to previous randomized trials of endovascular treatment for basilar artery occlusion, the ATTENTION trial was able to reinforce consecutive enrollment, resulting in a fast recruitment while minimizing crossovers. 

Furthermore, he pointed out that the overall results are consistent with modern era observational studies, large registries, and meta-analysis.

Commenting on the study, Joanna Wardlaw, MD, professor of applied neuroimaging at the University of Edinburgh (Scotland), and chair of the ESOC Planning Group, said: “This is a very important result, since it provides confirmation beyond doubt the benefit of thrombectomy versus medical therapy for basilar artery occlusion stroke up to 12 hours after onset.”

Dr. Wardlaw added: “The trial was large enough to provide clear results and to enable subgroup analyses; no subgroup did not benefit from thrombectomy.”

In a discussion after the presentation, Urs Fischer, MD, chair of the department of neurology at the University Hospital Basel, Switzerland, said he was not surprised by the results of the ATTENTION trial.

“We have been doing thrombectomy in patients with basilar artery occlusion now for 20 years, although trials are extremely important to answer these questions, so now we have some clear evidence,” Dr. Fischer said. “Nevertheless, there are some caveats, as this is an Asian population, but this is a proof of concept, and it is going in the right direction.”

The ATTENTION trial was sponsored by the First Affiliated Hospital of University of Science and Technology of China.

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

The Food and Drug Administration is limiting who can receive the Johnson & Johnson COVID-19 vaccine because of concerns about the risk of a rare blood clotting condition.

In a statement issued May 5, the FDA said the J&J vaccine should only be given to people 18 and older who don’t have access to other vaccines or for whom other vaccines are not clinically appropriate. People 18 and older can also get the J&J vaccine if they choose to because they wouldn’t otherwise receive any vaccine, the FDA said.

The FDA statement was similar to the recommendation made in December by a Centers for Disease Control and Prevention committee of experts.

The FDA said the decision was made after more information was shared about the occurrence of a rare blood clotting condition, thrombosis with thrombocytopenia syndrome (TTS), 1 or 2 weeks after people received the J&J vaccine. The finding “warrants limiting the authorized use of the vaccine,” the FDA said.

“We recognize that the Janssen COVID-19 vaccine still has a role in the current pandemic response in the United States and across the global community,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the statement.

“Our action reflects our updated analysis of the risk of TTS following administration of this vaccine and limits the use of the vaccine to certain individuals.”

The CDC says 16.9 million people are fully vaccinated with the J&J vaccine, compared with 76.5 million with Moderna and 126.3 million with Pfizer.

Through March 18, the CDC and FDA have detected 60 confirmed cases of TTS, including 9 fatal cases, ABC News reported.

The J&J vaccine was granted emergency authorization in February 2021. Health authorities hoped it would help spread vaccines across the nation because it only required one initial dose and didn’t need to be stored at extremely cold temperatures, unlike the two-dose Pfizer and Moderna vaccines.

But 2 months after authorization, the government paused its use for 10 days because of reports of TTS. In December 2021, the CDC’s Advisory Committee on Immunization Practices said the Pfizer and Moderna vaccines were preferred over J&J because J&J carried the rare risk of blood clots and bleeding in the brain.

The FDA said the cause of the blood clotting is not known. But the “known and potential benefits of the vaccine” outweigh the risks for those people now allowed to receive it, the FDA said.

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

The Food and Drug Administration is limiting who can receive the Johnson & Johnson COVID-19 vaccine because of concerns about the risk of a rare blood clotting condition.

In a statement issued May 5, the FDA said the J&J vaccine should only be given to people 18 and older who don’t have access to other vaccines or for whom other vaccines are not clinically appropriate. People 18 and older can also get the J&J vaccine if they choose to because they wouldn’t otherwise receive any vaccine, the FDA said.

The FDA statement was similar to the recommendation made in December by a Centers for Disease Control and Prevention committee of experts.

The FDA said the decision was made after more information was shared about the occurrence of a rare blood clotting condition, thrombosis with thrombocytopenia syndrome (TTS), 1 or 2 weeks after people received the J&J vaccine. The finding “warrants limiting the authorized use of the vaccine,” the FDA said.

“We recognize that the Janssen COVID-19 vaccine still has a role in the current pandemic response in the United States and across the global community,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the statement.

“Our action reflects our updated analysis of the risk of TTS following administration of this vaccine and limits the use of the vaccine to certain individuals.”

The CDC says 16.9 million people are fully vaccinated with the J&J vaccine, compared with 76.5 million with Moderna and 126.3 million with Pfizer.

Through March 18, the CDC and FDA have detected 60 confirmed cases of TTS, including 9 fatal cases, ABC News reported.

The J&J vaccine was granted emergency authorization in February 2021. Health authorities hoped it would help spread vaccines across the nation because it only required one initial dose and didn’t need to be stored at extremely cold temperatures, unlike the two-dose Pfizer and Moderna vaccines.

But 2 months after authorization, the government paused its use for 10 days because of reports of TTS. In December 2021, the CDC’s Advisory Committee on Immunization Practices said the Pfizer and Moderna vaccines were preferred over J&J because J&J carried the rare risk of blood clots and bleeding in the brain.

The FDA said the cause of the blood clotting is not known. But the “known and potential benefits of the vaccine” outweigh the risks for those people now allowed to receive it, the FDA said.

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

The Food and Drug Administration is limiting who can receive the Johnson & Johnson COVID-19 vaccine because of concerns about the risk of a rare blood clotting condition.

In a statement issued May 5, the FDA said the J&J vaccine should only be given to people 18 and older who don’t have access to other vaccines or for whom other vaccines are not clinically appropriate. People 18 and older can also get the J&J vaccine if they choose to because they wouldn’t otherwise receive any vaccine, the FDA said.

The FDA statement was similar to the recommendation made in December by a Centers for Disease Control and Prevention committee of experts.

The FDA said the decision was made after more information was shared about the occurrence of a rare blood clotting condition, thrombosis with thrombocytopenia syndrome (TTS), 1 or 2 weeks after people received the J&J vaccine. The finding “warrants limiting the authorized use of the vaccine,” the FDA said.

“We recognize that the Janssen COVID-19 vaccine still has a role in the current pandemic response in the United States and across the global community,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the statement.

“Our action reflects our updated analysis of the risk of TTS following administration of this vaccine and limits the use of the vaccine to certain individuals.”

The CDC says 16.9 million people are fully vaccinated with the J&J vaccine, compared with 76.5 million with Moderna and 126.3 million with Pfizer.

Through March 18, the CDC and FDA have detected 60 confirmed cases of TTS, including 9 fatal cases, ABC News reported.

The J&J vaccine was granted emergency authorization in February 2021. Health authorities hoped it would help spread vaccines across the nation because it only required one initial dose and didn’t need to be stored at extremely cold temperatures, unlike the two-dose Pfizer and Moderna vaccines.

But 2 months after authorization, the government paused its use for 10 days because of reports of TTS. In December 2021, the CDC’s Advisory Committee on Immunization Practices said the Pfizer and Moderna vaccines were preferred over J&J because J&J carried the rare risk of blood clots and bleeding in the brain.

The FDA said the cause of the blood clotting is not known. But the “known and potential benefits of the vaccine” outweigh the risks for those people now allowed to receive it, the FDA said.

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

Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.

Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.

Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.

The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.

“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.

The study was published online in JAMA Network Open.
 

Injury severity not a factor

An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.

Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.

Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.

Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.

Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.

TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).

Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.

Surprising rate of comorbidity in youth

Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).

Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.

Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).

“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”

While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.

“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.

Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.

That’s important because research suggests less than half of patients with TBI receive follow-up care.

“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.

In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.

Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.

“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.

The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.

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

Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.

Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.

Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.

The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.

“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.

The study was published online in JAMA Network Open.
 

Injury severity not a factor

An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.

Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.

Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.

Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.

Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.

TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).

Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.

Surprising rate of comorbidity in youth

Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).

Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.

Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).

“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”

While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.

“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.

Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.

That’s important because research suggests less than half of patients with TBI receive follow-up care.

“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.

In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.

Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.

“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.

The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.

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

Mild traumatic brain injury (TBI) is linked to a significantly increased risk for a host of subsequent cardiovascular, endocrine, neurologic, and psychiatric disorders, new research shows.

Incidence of hypertension, coronary heart disease, diabetes, stroke, depression, and dementia all began to increase soon after the brain injury and persisted over a decade in both mild and moderate to severe TBI.

Researchers found the multisystem comorbidities in all age groups, including in patients as young as 18. They also found that patients who developed multiple postinjury problems had higher mortality during the decade-long follow-up.

The findings suggest patients with TBI may require longer follow-up and proactive screening for multisystem disease, regardless of age or injury severity.

“The fact that both patients with mild and moderate to severe injuries both had long-term ongoing associations with comorbidities that continued over time and that they are cardiovascular, endocrine, neurologic, and behavioral health oriented was pretty striking,” study author Ross Zafonte, DO, PhD, president of Spaulding Rehab Hospital and professor and chair of physical medicine and rehab at Harvard Medical School, both in Boston, told this news organization.

The study was published online in JAMA Network Open.
 

Injury severity not a factor

An estimated 2.8 million individuals in the United States experience TBI every year. Worldwide, the figure may be as high as 74 million.

Studies have long suggested a link between brain injury and subsequent neurologic disorders, but research suggesting a possible link to cardiovascular and endocrine problems has recently gained attention.

Building on a 2021 study that showed increased incidence of cardiovascular issues following a concussion, the researchers examined medical records of previously healthy patients treated for TBI between 2000 and 2015 who also had at least 1 follow-up visit between 6 months and 10 years after the initial injury.

Researchers analyzed data from 13,053 individuals – 4,351 with mild injury (mTBI), 4351 with moderate to severe injury (msTBI), and 4351 with no TBI. The most common cause of injury was a fall. Patients with sports-related injuries were excluded.

Incidence of hypertension was significantly higher among patients with mTBI (hazard ratio, 2.5; 95% confidence interval, 2.1-2.9) and msTBI (HR, 2.4; 95% CI, 2.0-2.9), compared with the unaffected group. Risk for other cardiovascular problems, including hyperlipidemia, obesity, and coronary artery disease, were also higher in the affected groups.

TBI patients also reported higher incidence of endocrine diseases, including diabetes (mTBI: HR, 1.9; 95% CI, 1.4-2.7; msTBI: HR, 1.9; 95% CI, 1.4-2.6). Elevated risk for ischemic stroke or transient ischemic attack was also increased (mTBI: HR, 2.2; 95% CI, 1.4-3.3; msTBI: HR, 3.6; 95% CI, 2.4-5.3).

Regardless of injury severity, patients with TBI had a higher risk for neurologic and psychiatric diseases, particularly depression, dementia, and psychotic disorders. “This tells us that mild TBI is not clean of events,” Dr. Zafonte said.

Surprising rate of comorbidity in youth

Investigators found increased risk for posttrauma comorbidities in all age groups, but researchers were struck by the high rates in younger patients, aged 18-40. Compared with age-matched individuals with no TBI history, hypertension risk was nearly six times higher in those with mTBI (HR, 5.9; 95% CI, 3.9-9.1) and nearly four times higher in patients with msTBI (HR, 3.9; 95% CI, 2.5-6.1).

Rates of hyperlipidemia and diabetes were also higher in younger patients in the mTBI group and posttraumatic seizures and psychiatric disorders were elevated regardless of TBI severity.

Overall, patients with msTBI, but not those with mTBI, were at higher risk for mortality, compared with the unexposed group (432 deaths [9.9%] vs. 250 deaths [5.7%]; P < .001).

“It’s clear that what we may be dealing with is that it holds up even for the younger people,” Dr. Zafonte said. “We used to think brain injury risk is worse in the severe cases, which it is, and it’s worse later on among those who are older, which it is. But our younger folks don’t get away either.”

While the study offers associations between TBI and multisystem health problems, Dr. Zafonte said it’s impossible to say at this point whether the brain injury caused the increased risk for cardiovascular or endocrine problems. Other organ injuries sustained in the trauma may be a contributing factor.

“Further data is needed to elucidate the mechanism and the causative relationships, which we do not have here,” he said.

Many of the postinjury comorbidities emerged a median of 3.5 years after TBI, regardless of severity. But some of the cardiovascular and psychiatric conditions emerged far sooner than that.

That’s important because research suggests less than half of patients with TBI receive follow-up care.

“It does make sense for folks who are interacting with people who’ve had a TBI to be suspicious of medical comorbidities relatively early on, within the first couple of years,” Dr. Zafonte said.

In an invited commentary, Vijay Krishnamoorthy, MD, MPH, PhD, Duke University, Durham, N.C., and Monica S. Vavilala, MD, University of Washington, Seattle, highlight some of the study’s limitations, including a lack of information on comorbidity severity and the lack of a matched group of patients who experienced non-head trauma.

Despite those limitations, the study offers important information on how TBI may affect organs beyond the brain, they noted.

“These observations, if replicated in future studies, raise intriguing implications in the future care of patients with TBI, including heightened chronic disease-screening measures and possibly enhanced guidelines for chronic extracranial organ system care for patients who experience TBI,” Dr. Krishnamoorthy and Dr. Vavilala wrote.

The study received no specific funding. Dr. Zafonte reported having received personal fees from Springer/Demos, serving on scientific advisory boards for Myomo and OnCare and has received funding from the Football Players Health Study at Harvard, funded in part by the National Football League Players Association. Dr. Krishnamoorthy and Dr. Vavilala disclosed no relevant financial relationships.

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

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

More than 40 medical conditions were positively associated with having a new diagnosis of osteoarthritis according to research presented at the OARSI 2022 World Congress.

“Some of the associations that we have found are previously known, such as of course, obesity, which is a known risk factor, but also other musculoskeletal conditions, depression, and reflux disease,” said Anne Kamps, an MD and PhD student at Erasmus University Medical Centre in Rotterdam, the Netherlands.

“But there are also some remarkable associations that we have found that are less well known, such as liver cirrhosis, thromboembolic disease, sinusitis, allergy, and migraine,” said Dr. Kamps during her presentation at the conference, sponsored by the Osteoarthritis Research Society International.

The results are “very interesting starting points for future research, because of course, this was an explorative study,” she added. Indeed, is still not known whether the comorbidities found share the same risk factors as OA, or if they have a causal effect and add to development of osteoarthritis.
 

Comorbidity and OA

One of the issues in managing osteoarthritis so far is that it’s often addressed as one disease, commented Andrea Dell’isola, PT, PhD, a postdoctoral researcher from Lund University who was not involved in the study.

“All of the treatments that have been developed and the treatment process are tailored to take care of one single disease,” he explained. However, “when we look at the characteristics of people with osteoarthritis, we see that roughly 70% of them have other conditions on top of their joint disease.” This high comorbidity rate is significantly higher than in “healthy” people of the same age and sex, he added.

“So, this means that either there is something linked to osteoarthritis that makes people frailer and more likely to develop other diseases, or there may be links between these other diseases, that we often call comorbidities, and osteoarthritis,” Dr. Dell’isola observed.

While the work Dr. Kamps presented looked at the rate of comorbidities that existed before the diagnosis of OA, some of Dr. Dell’isola’s recent research has considered the rate of developing comorbid disease in the years following an OA diagnosis. Associations were found between having hip or knee OA and an increased risk for coexisting depression, cardiovascular diseases, back pain, osteoporosis, and, in the case of knee OA only, diabetes. “It’s interesting to see that certain diseases seem to have a bidirectional association. This means that they can both precede and follow osteoarthritis,” said Dr. Dell’isola. These are just associations, not causation, he stressed, but they might help identify people visiting a doctor for other reasons who may be at risk for developing OA.

“One of the biggest challenges is that once a person develops osteoarthritis, there is not any treatment that can really change their disease,” he added.

Perhaps, “if we can target certain conditions that increase the risk of developing osteoarthritis, and maybe convince people to exercise earlier, or undergo some lifestyle changes early on, we can maybe prevent or delay the onset of the disease,” he suggested.
 

Results and perspective

Dr. Kamps and associates performed a nested case-control study using data from a large Dutch general practice database. All new cases of OA – which included hip, knee, and other peripheral OA – that were logged between the start of 2006 and the end of 2019 were considered and matched to one to four control subjects of a similar age, sex, and type of general practice. In all, there were just under 80,000 people with newly diagnosed OA who were matched to just over 318,000 controls; the mean age in both groups was 64 years.

Of 58 comorbidities that were assessed, 42 showed a positive association with OA and had odds ratios of 1 or more. The highest associations were found for fibromyalgia (OR, 1.9), obesity (1.8), polymyalgia rheumatica (1.5), spinal disc herniation (1.4), and gout (1.4). A further 13 comorbidities had an OR of about 1, and 3 (all neuropsychiatric conditions – dementia, schizophrenia, and multiple sclerosis) had an OR of below 1.

Dr. Kamps conceded that this type of research has its limitations, the two most important being the coding behavior of the GP and the consulting behavior of patients.

“It’s known that the prevalence of osteoarthritis is underestimated if you only use the diagnostic codes, because some GPs will write the diagnosis in free text or use symptom ICPC codes,” she said.

“We have matched on general practice, so the cases and controls were from the same general practice and therefore we hope that this potential underestimation is balanced and did not affect our odds ratios.”

One of the important outcomes for this research is that it will hopefully be used to inform future clinical practice guidelines, said Dr. Dell’isola.

“Guidelines in osteoarthritis report that is important to screen for comorbidities, but they give no indication on how to deal with the presence of multimorbidity,” he added. Looking at which comorbidities may be associated with OA diagnosis could potentially help to give a bit more of a prescriptive guide on what to look out for.

“Maybe people with a certain disease profile should be screened a bit more often by their doctor. For example, if someone has their blood pressure and diabetes under control, maybe there should be also a bit more attention to their joint health and encouragement to do exercise, not only for being active per se, but maybe also to reinforce their lower limbs,” he explained.

The study was funded by the Foundation for Research in Rheumatology (FOREUM). Dr. Kamps and Dr. Dell’isola, had no conflicts of interest to disclose.
 

In patients undergoing transcatheter aortic valve replacement (TAVR), the incidence of leaflet thrombosis was numerically lower in those treated with the anticoagulant edoxaban for 6 months after the procedure than in those who received dual antiplatelet therapy, although the difference was not statistically significant, in the ADAPT-TAVR study.

There was no difference in new cerebral thromboembolism or neurologic/neurocognitive function between the two groups in the study.

Also, there was no significant relation between subclinical leaflet thrombosis and increased risk for cerebral thromboembolism and neurologic dysfunction.

The ADAPT-TAVR trial was presented April 4 at the American College of Cardiology (ACC) 2022 Scientific Session by Duk-Woo Park, MD, Asan Medical Center, Seoul, South Korea. It was simultaneously published online in Circulation.

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

In patients undergoing transcatheter aortic valve replacement (TAVR), the incidence of leaflet thrombosis was numerically lower in those treated with the anticoagulant edoxaban for 6 months after the procedure than in those who received dual antiplatelet therapy, although the difference was not statistically significant, in the ADAPT-TAVR study.

There was no difference in new cerebral thromboembolism or neurologic/neurocognitive function between the two groups in the study.

Also, there was no significant relation between subclinical leaflet thrombosis and increased risk for cerebral thromboembolism and neurologic dysfunction.

The ADAPT-TAVR trial was presented April 4 at the American College of Cardiology (ACC) 2022 Scientific Session by Duk-Woo Park, MD, Asan Medical Center, Seoul, South Korea. It was simultaneously published online in Circulation.

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

In patients undergoing transcatheter aortic valve replacement (TAVR), the incidence of leaflet thrombosis was numerically lower in those treated with the anticoagulant edoxaban for 6 months after the procedure than in those who received dual antiplatelet therapy, although the difference was not statistically significant, in the ADAPT-TAVR study.

There was no difference in new cerebral thromboembolism or neurologic/neurocognitive function between the two groups in the study.

Also, there was no significant relation between subclinical leaflet thrombosis and increased risk for cerebral thromboembolism and neurologic dysfunction.

The ADAPT-TAVR trial was presented April 4 at the American College of Cardiology (ACC) 2022 Scientific Session by Duk-Woo Park, MD, Asan Medical Center, Seoul, South Korea. It was simultaneously published online in Circulation.

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

The antifibrinolytic tranexamic acid (TXA) reduced serious bleeding without a significant effect on major vascular outcomes in patients undergoing noncardiac surgery at risk for these complications in the POISE-3 trial.

TXA cut the primary efficacy outcome of life-threatening, major, and critical organ bleeding at 30 days by 24% compared with placebo (9.1% vs. 11.7%; hazard ratio [HR], 0.76; P < .0001).

The primary safety outcome of myocardial injury after noncardiac surgery (MINS), nonhemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism (VTE) at 30 days occurred in 14.2% vs.. 13.9% of patients, respectively (HR, 1.023). This failed, however, to meet the study›s threshold to prove TXA noninferior to placebo (one-sided P = .044).

There was no increased risk for death or stroke with TXA, according to results published April 2 in the New England Journal of Medicine.

Principal investigator P.J. Devereaux, MD, PhD, Population Health Research Institute and McMaster University, Hamilton, Ontario, Canada, pointed out that there is only a 4.4% probability that the composite vascular outcome hazard ratio was above the noninferiority margin and that just 10 events separated the two groups (649 vs.. 639).

“Healthcare providers and patients will have to weigh a clear beneficial reduction in the composite bleeding outcome, which is an absolute difference of 2.7%, a result that was highly statistically significant, versus a low probability of a small increase in risk of the composite vascular endpoint, with an absolute difference of 0.3%,” a nonsignificant result, Dr. Devereaux said during the formal presentation of the results at the hybrid annual scientific sessions of the American College of Cardiology.

The findings, he said, should also be put in the context that 300 million adults have a major surgery each year worldwide and most don’t receive TXA. At the same time, there’s an annual global shortage of 30 million blood product units, and surgical bleeding accounts for up to 40% of all transfusions.

“POISE-3 identifies that use of TXA could avoid upwards of 8 million bleeding events resulting in transfusion on an annual basis, indicating potential for large public health and clinical benefit if TXA become standard practice in noncardiac surgery,” Dr. Devereaux said during the late-breaking trial session.

TXA is indicated for heavy menstrual bleeding and hemophilia and has been used in cardiac surgery, but it is increasingly being used in noncardiac surgeries. As previously reported, POISE showed that the beta-blocker metoprolol lowered the risk for myocardial infarction (MI) but increased the risk for severe stroke and overall death, whereas in POISE-2, perioperative low-dose aspirin lowered the risk for MI but was linked to more major bleeding.

The cumulative data have not shown an increased risk for thrombotic events in other settings, Dr. Devereaux told this news organization.

“I’m a cardiologist, and I think that we’ve been guilty at times of always only focusing on the thrombotic side of the equation and ignoring that bleeding is a very important aspect of the circulatory system,” he said. “And I think this shows for the first time clear unequivocal evidence that there’s a cheap, very encouraging, safe way to prevent this.”

“An important point is that if you can give tranexamic acid and prevent bleeding in your cardiac patients having noncardiac surgery, then you can prevent the delay of reinitiating their anticoagulants and their antiplatelets after surgery and getting them back on the medications that are important for them to prevent their cardiovascular event,” Dr. Devereaux added.

Discussant Michael J. Mack, MD, commented that TXA, widely used in cardiac surgery, is an old, inexpensive drug that “should be more widely used in noncardiac surgery.” Dr. Mack, from Baylor Scott & White Health, Dallas, added that he would limit it to major noncardiac surgery.

International trial

PeriOperative ISchemic Evaluation-3 (POISE-3) investigators at 114 hospitals in 22 countries (including countries in North and South America, Europe, and Africa; Russia; India; and Australia) randomly assigned 9,535 patients, aged 45 years or older, with or at risk for cardiovascular and bleeding complications to receive a TXA 1-g intravenous bolus or placebo at the start and end of inpatient noncardiac surgery.

Patients taking at least one long-term antihypertensive medication were also randomly assigned to a perioperative hypotension- or hypertension-avoidance strategy, which differ in the use of antihypertensives on the morning of surgery and the first 2 days after surgery, and in the target mean arterial pressure during surgery. Results from these cohorts will be presented in a separate session on April 4.

The study had planned to enroll 10,000 patients but was stopped early by the steering committee because of financial constraints resulting from slow enrollment during the pandemic. The decision was made without knowledge of the trial results but with knowledge that aggregate composite bleeding and vascular outcomes were higher than originally estimated, Dr. Devereaux noted.

Among all participants, the mean age was 70 years, 56% were male, almost a third had coronary artery disease, 15% had peripheral artery disease, and 8% had a prior stroke. About 80% were undergoing major surgery. Adherence to the study medications was 96.3% in both groups.

Secondary bleeding outcomes were lower in the TXA and placebo groups, including bleeding independently associated with mortality after surgery (8.7% vs. 11.3%), life-threatening bleeding (1.6% vs. 1.7%), major bleeding (7.6% vs. 10.4%), and critical organ bleeding (0.3% vs. 0.4%).

Importantly, the TXA group had significantly lower rates of International Society on Thrombosis and Haemostasis major bleeding (6.6% vs. 8.7%; P = .0001) and the need for transfusion of 1 or more units of packed red blood cells (9.4% vs. 12.0%; P <.0001), Dr. Devereaux noted.

In terms of secondary vascular outcomes, there were no significant differences between the TXA and placebo groups in rates of MINS (12.8% vs. 12.6%), MINS not fulfilling definition of MI (both 11.5%), MI (1.4% vs. 1.1%), and the net risk-benefit outcome (a composite of vascular death and nonfatal life-threatening, major, or critical organ bleeding, MINS, stroke, peripheral arterial thrombosis, and symptomatic proximal VTE; 20.7% vs. 21.9%).

The two groups had similar rates of all-cause (1.1% vs. 1.2%) and vascular (0.5% vs. 0.6%) mortality.

There also were no significant differences in other tertiary outcomes, such as acute kidney injury (14.1% vs. 13.7%), rehospitalization for vascular reasons (1.8% vs. 1.6%), or seizures (0.2% vs. <0.1%). The latter has been a concern, with the risk reported to increase with higher doses.

Subgroup analyses

Preplanned subgroup analyses showed a benefit for TXA over placebo for the primary efficacy outcome in orthopedic and nonorthopedic surgery and in patients with hemoglobin level below 120 g/L or 120 g/L or higher, with an estimated glomerular filtration rate less than 45 mL/min/1.73 m ²  or 45 mL/min/1.73 m ²  or higher, or with an N-terminal pro– B-type natriuretic peptide level below 200 ng/L or 200 ng/L or higher.

For the primary safety outcome, the benefit favored placebo but the interaction was not statistically significant for any of the four subgroups.

A post hoc subgroup analysis also showed similar results across the major categories of surgery, including general, vascular, urologic, and gynecologic, Dr. Devereaux told this news organization.

Although TXA is commonly used in orthopedic procedures, Dr. Devereaux noted, in other types of surgeries, “it’s not used at all.” But because TXA “is so cheap, and we can apply it to a broad population, even at an economic level it looks like it’s a winner to give to almost all patients having noncardiac surgery.”

The team also recently published a risk prediction tool that can help estimate a patient’s baseline risk for bleeding.

“So just using a model, which will bring together the patient’s type of surgery and their risk factors, you can look to see, okay, this is enough risk of bleeding, I’m just going to give tranexamic acid,” he said. “We will also be doing economic analyses because blood is also not cheap.”

The study was funded by the Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and the Research Grant Council (Hong Kong). Dr. Devereaux reports research/research grants from Abbott Diagnostics, Philips Healthcare, Roche Diagnostics, and Siemens. Dr. Mack reports receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

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

The antifibrinolytic tranexamic acid (TXA) reduced serious bleeding without a significant effect on major vascular outcomes in patients undergoing noncardiac surgery at risk for these complications in the POISE-3 trial.

TXA cut the primary efficacy outcome of life-threatening, major, and critical organ bleeding at 30 days by 24% compared with placebo (9.1% vs. 11.7%; hazard ratio [HR], 0.76; P < .0001).

The primary safety outcome of myocardial injury after noncardiac surgery (MINS), nonhemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism (VTE) at 30 days occurred in 14.2% vs.. 13.9% of patients, respectively (HR, 1.023). This failed, however, to meet the study›s threshold to prove TXA noninferior to placebo (one-sided P = .044).

There was no increased risk for death or stroke with TXA, according to results published April 2 in the New England Journal of Medicine.

Principal investigator P.J. Devereaux, MD, PhD, Population Health Research Institute and McMaster University, Hamilton, Ontario, Canada, pointed out that there is only a 4.4% probability that the composite vascular outcome hazard ratio was above the noninferiority margin and that just 10 events separated the two groups (649 vs.. 639).

“Healthcare providers and patients will have to weigh a clear beneficial reduction in the composite bleeding outcome, which is an absolute difference of 2.7%, a result that was highly statistically significant, versus a low probability of a small increase in risk of the composite vascular endpoint, with an absolute difference of 0.3%,” a nonsignificant result, Dr. Devereaux said during the formal presentation of the results at the hybrid annual scientific sessions of the American College of Cardiology.

The findings, he said, should also be put in the context that 300 million adults have a major surgery each year worldwide and most don’t receive TXA. At the same time, there’s an annual global shortage of 30 million blood product units, and surgical bleeding accounts for up to 40% of all transfusions.

“POISE-3 identifies that use of TXA could avoid upwards of 8 million bleeding events resulting in transfusion on an annual basis, indicating potential for large public health and clinical benefit if TXA become standard practice in noncardiac surgery,” Dr. Devereaux said during the late-breaking trial session.

TXA is indicated for heavy menstrual bleeding and hemophilia and has been used in cardiac surgery, but it is increasingly being used in noncardiac surgeries. As previously reported, POISE showed that the beta-blocker metoprolol lowered the risk for myocardial infarction (MI) but increased the risk for severe stroke and overall death, whereas in POISE-2, perioperative low-dose aspirin lowered the risk for MI but was linked to more major bleeding.

The cumulative data have not shown an increased risk for thrombotic events in other settings, Dr. Devereaux told this news organization.

“I’m a cardiologist, and I think that we’ve been guilty at times of always only focusing on the thrombotic side of the equation and ignoring that bleeding is a very important aspect of the circulatory system,” he said. “And I think this shows for the first time clear unequivocal evidence that there’s a cheap, very encouraging, safe way to prevent this.”

“An important point is that if you can give tranexamic acid and prevent bleeding in your cardiac patients having noncardiac surgery, then you can prevent the delay of reinitiating their anticoagulants and their antiplatelets after surgery and getting them back on the medications that are important for them to prevent their cardiovascular event,” Dr. Devereaux added.

Discussant Michael J. Mack, MD, commented that TXA, widely used in cardiac surgery, is an old, inexpensive drug that “should be more widely used in noncardiac surgery.” Dr. Mack, from Baylor Scott & White Health, Dallas, added that he would limit it to major noncardiac surgery.

International trial

PeriOperative ISchemic Evaluation-3 (POISE-3) investigators at 114 hospitals in 22 countries (including countries in North and South America, Europe, and Africa; Russia; India; and Australia) randomly assigned 9,535 patients, aged 45 years or older, with or at risk for cardiovascular and bleeding complications to receive a TXA 1-g intravenous bolus or placebo at the start and end of inpatient noncardiac surgery.

Patients taking at least one long-term antihypertensive medication were also randomly assigned to a perioperative hypotension- or hypertension-avoidance strategy, which differ in the use of antihypertensives on the morning of surgery and the first 2 days after surgery, and in the target mean arterial pressure during surgery. Results from these cohorts will be presented in a separate session on April 4.

The study had planned to enroll 10,000 patients but was stopped early by the steering committee because of financial constraints resulting from slow enrollment during the pandemic. The decision was made without knowledge of the trial results but with knowledge that aggregate composite bleeding and vascular outcomes were higher than originally estimated, Dr. Devereaux noted.

Among all participants, the mean age was 70 years, 56% were male, almost a third had coronary artery disease, 15% had peripheral artery disease, and 8% had a prior stroke. About 80% were undergoing major surgery. Adherence to the study medications was 96.3% in both groups.

Secondary bleeding outcomes were lower in the TXA and placebo groups, including bleeding independently associated with mortality after surgery (8.7% vs. 11.3%), life-threatening bleeding (1.6% vs. 1.7%), major bleeding (7.6% vs. 10.4%), and critical organ bleeding (0.3% vs. 0.4%).

Importantly, the TXA group had significantly lower rates of International Society on Thrombosis and Haemostasis major bleeding (6.6% vs. 8.7%; P = .0001) and the need for transfusion of 1 or more units of packed red blood cells (9.4% vs. 12.0%; P <.0001), Dr. Devereaux noted.

In terms of secondary vascular outcomes, there were no significant differences between the TXA and placebo groups in rates of MINS (12.8% vs. 12.6%), MINS not fulfilling definition of MI (both 11.5%), MI (1.4% vs. 1.1%), and the net risk-benefit outcome (a composite of vascular death and nonfatal life-threatening, major, or critical organ bleeding, MINS, stroke, peripheral arterial thrombosis, and symptomatic proximal VTE; 20.7% vs. 21.9%).

The two groups had similar rates of all-cause (1.1% vs. 1.2%) and vascular (0.5% vs. 0.6%) mortality.

There also were no significant differences in other tertiary outcomes, such as acute kidney injury (14.1% vs. 13.7%), rehospitalization for vascular reasons (1.8% vs. 1.6%), or seizures (0.2% vs. <0.1%). The latter has been a concern, with the risk reported to increase with higher doses.

Subgroup analyses

Preplanned subgroup analyses showed a benefit for TXA over placebo for the primary efficacy outcome in orthopedic and nonorthopedic surgery and in patients with hemoglobin level below 120 g/L or 120 g/L or higher, with an estimated glomerular filtration rate less than 45 mL/min/1.73 m ²  or 45 mL/min/1.73 m ²  or higher, or with an N-terminal pro– B-type natriuretic peptide level below 200 ng/L or 200 ng/L or higher.

For the primary safety outcome, the benefit favored placebo but the interaction was not statistically significant for any of the four subgroups.

A post hoc subgroup analysis also showed similar results across the major categories of surgery, including general, vascular, urologic, and gynecologic, Dr. Devereaux told this news organization.

Although TXA is commonly used in orthopedic procedures, Dr. Devereaux noted, in other types of surgeries, “it’s not used at all.” But because TXA “is so cheap, and we can apply it to a broad population, even at an economic level it looks like it’s a winner to give to almost all patients having noncardiac surgery.”

The team also recently published a risk prediction tool that can help estimate a patient’s baseline risk for bleeding.

“So just using a model, which will bring together the patient’s type of surgery and their risk factors, you can look to see, okay, this is enough risk of bleeding, I’m just going to give tranexamic acid,” he said. “We will also be doing economic analyses because blood is also not cheap.”

The study was funded by the Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and the Research Grant Council (Hong Kong). Dr. Devereaux reports research/research grants from Abbott Diagnostics, Philips Healthcare, Roche Diagnostics, and Siemens. Dr. Mack reports receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

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

The antifibrinolytic tranexamic acid (TXA) reduced serious bleeding without a significant effect on major vascular outcomes in patients undergoing noncardiac surgery at risk for these complications in the POISE-3 trial.

TXA cut the primary efficacy outcome of life-threatening, major, and critical organ bleeding at 30 days by 24% compared with placebo (9.1% vs. 11.7%; hazard ratio [HR], 0.76; P < .0001).

The primary safety outcome of myocardial injury after noncardiac surgery (MINS), nonhemorrhagic stroke, peripheral arterial thrombosis, and symptomatic proximal venous thromboembolism (VTE) at 30 days occurred in 14.2% vs.. 13.9% of patients, respectively (HR, 1.023). This failed, however, to meet the study›s threshold to prove TXA noninferior to placebo (one-sided P = .044).

There was no increased risk for death or stroke with TXA, according to results published April 2 in the New England Journal of Medicine.

Principal investigator P.J. Devereaux, MD, PhD, Population Health Research Institute and McMaster University, Hamilton, Ontario, Canada, pointed out that there is only a 4.4% probability that the composite vascular outcome hazard ratio was above the noninferiority margin and that just 10 events separated the two groups (649 vs.. 639).

“Healthcare providers and patients will have to weigh a clear beneficial reduction in the composite bleeding outcome, which is an absolute difference of 2.7%, a result that was highly statistically significant, versus a low probability of a small increase in risk of the composite vascular endpoint, with an absolute difference of 0.3%,” a nonsignificant result, Dr. Devereaux said during the formal presentation of the results at the hybrid annual scientific sessions of the American College of Cardiology.

The findings, he said, should also be put in the context that 300 million adults have a major surgery each year worldwide and most don’t receive TXA. At the same time, there’s an annual global shortage of 30 million blood product units, and surgical bleeding accounts for up to 40% of all transfusions.

“POISE-3 identifies that use of TXA could avoid upwards of 8 million bleeding events resulting in transfusion on an annual basis, indicating potential for large public health and clinical benefit if TXA become standard practice in noncardiac surgery,” Dr. Devereaux said during the late-breaking trial session.

TXA is indicated for heavy menstrual bleeding and hemophilia and has been used in cardiac surgery, but it is increasingly being used in noncardiac surgeries. As previously reported, POISE showed that the beta-blocker metoprolol lowered the risk for myocardial infarction (MI) but increased the risk for severe stroke and overall death, whereas in POISE-2, perioperative low-dose aspirin lowered the risk for MI but was linked to more major bleeding.

The cumulative data have not shown an increased risk for thrombotic events in other settings, Dr. Devereaux told this news organization.

“I’m a cardiologist, and I think that we’ve been guilty at times of always only focusing on the thrombotic side of the equation and ignoring that bleeding is a very important aspect of the circulatory system,” he said. “And I think this shows for the first time clear unequivocal evidence that there’s a cheap, very encouraging, safe way to prevent this.”

“An important point is that if you can give tranexamic acid and prevent bleeding in your cardiac patients having noncardiac surgery, then you can prevent the delay of reinitiating their anticoagulants and their antiplatelets after surgery and getting them back on the medications that are important for them to prevent their cardiovascular event,” Dr. Devereaux added.

Discussant Michael J. Mack, MD, commented that TXA, widely used in cardiac surgery, is an old, inexpensive drug that “should be more widely used in noncardiac surgery.” Dr. Mack, from Baylor Scott & White Health, Dallas, added that he would limit it to major noncardiac surgery.

International trial

PeriOperative ISchemic Evaluation-3 (POISE-3) investigators at 114 hospitals in 22 countries (including countries in North and South America, Europe, and Africa; Russia; India; and Australia) randomly assigned 9,535 patients, aged 45 years or older, with or at risk for cardiovascular and bleeding complications to receive a TXA 1-g intravenous bolus or placebo at the start and end of inpatient noncardiac surgery.

Patients taking at least one long-term antihypertensive medication were also randomly assigned to a perioperative hypotension- or hypertension-avoidance strategy, which differ in the use of antihypertensives on the morning of surgery and the first 2 days after surgery, and in the target mean arterial pressure during surgery. Results from these cohorts will be presented in a separate session on April 4.

The study had planned to enroll 10,000 patients but was stopped early by the steering committee because of financial constraints resulting from slow enrollment during the pandemic. The decision was made without knowledge of the trial results but with knowledge that aggregate composite bleeding and vascular outcomes were higher than originally estimated, Dr. Devereaux noted.

Among all participants, the mean age was 70 years, 56% were male, almost a third had coronary artery disease, 15% had peripheral artery disease, and 8% had a prior stroke. About 80% were undergoing major surgery. Adherence to the study medications was 96.3% in both groups.

Secondary bleeding outcomes were lower in the TXA and placebo groups, including bleeding independently associated with mortality after surgery (8.7% vs. 11.3%), life-threatening bleeding (1.6% vs. 1.7%), major bleeding (7.6% vs. 10.4%), and critical organ bleeding (0.3% vs. 0.4%).

Importantly, the TXA group had significantly lower rates of International Society on Thrombosis and Haemostasis major bleeding (6.6% vs. 8.7%; P = .0001) and the need for transfusion of 1 or more units of packed red blood cells (9.4% vs. 12.0%; P <.0001), Dr. Devereaux noted.

In terms of secondary vascular outcomes, there were no significant differences between the TXA and placebo groups in rates of MINS (12.8% vs. 12.6%), MINS not fulfilling definition of MI (both 11.5%), MI (1.4% vs. 1.1%), and the net risk-benefit outcome (a composite of vascular death and nonfatal life-threatening, major, or critical organ bleeding, MINS, stroke, peripheral arterial thrombosis, and symptomatic proximal VTE; 20.7% vs. 21.9%).

The two groups had similar rates of all-cause (1.1% vs. 1.2%) and vascular (0.5% vs. 0.6%) mortality.

There also were no significant differences in other tertiary outcomes, such as acute kidney injury (14.1% vs. 13.7%), rehospitalization for vascular reasons (1.8% vs. 1.6%), or seizures (0.2% vs. <0.1%). The latter has been a concern, with the risk reported to increase with higher doses.

Subgroup analyses

Preplanned subgroup analyses showed a benefit for TXA over placebo for the primary efficacy outcome in orthopedic and nonorthopedic surgery and in patients with hemoglobin level below 120 g/L or 120 g/L or higher, with an estimated glomerular filtration rate less than 45 mL/min/1.73 m ²  or 45 mL/min/1.73 m ²  or higher, or with an N-terminal pro– B-type natriuretic peptide level below 200 ng/L or 200 ng/L or higher.

For the primary safety outcome, the benefit favored placebo but the interaction was not statistically significant for any of the four subgroups.

A post hoc subgroup analysis also showed similar results across the major categories of surgery, including general, vascular, urologic, and gynecologic, Dr. Devereaux told this news organization.

Although TXA is commonly used in orthopedic procedures, Dr. Devereaux noted, in other types of surgeries, “it’s not used at all.” But because TXA “is so cheap, and we can apply it to a broad population, even at an economic level it looks like it’s a winner to give to almost all patients having noncardiac surgery.”

The team also recently published a risk prediction tool that can help estimate a patient’s baseline risk for bleeding.

“So just using a model, which will bring together the patient’s type of surgery and their risk factors, you can look to see, okay, this is enough risk of bleeding, I’m just going to give tranexamic acid,” he said. “We will also be doing economic analyses because blood is also not cheap.”

The study was funded by the Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and the Research Grant Council (Hong Kong). Dr. Devereaux reports research/research grants from Abbott Diagnostics, Philips Healthcare, Roche Diagnostics, and Siemens. Dr. Mack reports receiving research grants from Abbott Vascular, Edwards Lifesciences, and Medtronic.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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

Regardless of the pandemic’s sometimes mercurial behavior, the cardiology community appears set to reclaim valued traditions perhaps taken for granted in the pre-COVID era.

They include the bustling scientific congress and its myriad educational and networking prospects, along with pleiotropic effects like unplanned reunions with colleagues and catching up face-to-face with old friends.

That seems evident in the growing number of registrants for live attendance at at the annual scientific sessions of the American College of Cardiology, set for this Saturday through Monday in Washington as well as virtually, for a global reach that was unattainable in the pre-COVID era.

Registrations had hit the 11,000 mark and were picking up speed in recent weeks, ACC 2022 cochair Pamela B. Morris, MD, Medical University of South Carolina, Charleston, said at a mid-March presentation to the media.

They had reached about 12,880 and were still climbing a week before the conference, the ACC confirmed to this news organization. By then the professional registration had surpassed 9,900, of whom more than two-thirds reported plans to attend in person.

Dr. Morris said there had been 117 international submissions for what turned out to be 39 coveted spots on the meeting’s Late-Breaking Clinical Trial (LBCT) and Featured Clinical Research agenda spread across eight separate sessions.

On-site participants at the Walter E. Washington Convention Center should head for the Main Tent in Hall D for all LBCT presentations; venues for the Featured Clinical Research sessions are as noted below. Their real-time virtual equivalents will reside on the online platform’s Hot Topics channel. All noted session times are Eastern Daylight Time.
 

Saturday, April 2, 9:30 a.m.–10:30 a.m. Joint American College of Cardiology/Journal of the American College of Cardiology LBCT (I)

Leading off the conference’s first LBCT session, the randomized VALOR-HCM trial explored whether 16 weeks of mavacamten (MyoKardia) could help patients with severe obstructive hypertrophic cardiomyopathy (HCM) avoid septal reduction therapy, either surgical or by alcohol ablation.

The 22-center VALOR-HCM trial with an estimated enrollment of 100 follows EXPLORER-HCM, which in 2020 suggested the novel myosin-inhibiting agent could improve symptoms, exercise capacity, cardiac remodeling, and quality of life in such patients.

Simply advising people with heart failure (HF) to consume less salt is one thing, but it’s another to show them clinical trial evidence that it might help keep them out of the hospital. The SODIUM-HF (Study of Dietary Intervention Under 100 mmol in Heart Failure) study, conducted at 27 sites in six countries, sought to provide that evidence.

The trial randomly assigned 1,000 patients with NYHA class 2-3 HF to consume no more than 1,500 mg/day in sodium or to receive standard advice to limit sodium intake, and followed them for a year for the endpoint of death from any cause, cardiovascular (CV) hospitalization, or CV emergency department visit.

SODIUM-HF “may provide a rigorous evidence base for sodium restriction in patients with heart failure and may truly change our practice and how we recommend dietary modification,” ACC 2022 vice chair Douglas E. Drachman, MD, Massachusetts General Hospital, Boston, said at the media presentation.

In the same session, the CHAP (Chronic Hypertension and Pregnancy) study explored whether blood pressure (BP) control in pregnant women with new or untreated chronic hypertension could help avert preeclampsia, poor fetal outcomes, and other adverse events.

CHAP assigned about 2,400 women to receive either stepwise antihypertensive therapy to a BP goal of 140/90 mm Hg or lower or no such meds unless their BP reached or exceeded 160/105 mm Hg. Stepwise therapy featured either labetalol or extended-release nifedipine to start, the other agent added as necessary.

The LBCT block also includes the POISE-3 (Perioperative Ischemic Evaluation-3) comparison of the hemostatic agent tranexamic acid vs. placebo in nearly 10,000 patients undergoing noncardiac surgery. A separate randomization of the same cohort, to be reported at a Monday LBCT session, compared pre- and perioperative BP-control strategies.
 

Saturday, April 2, 12:00 p.m.–1:15 p.m. Featured Clinical Research I. Room 143A

This session features a subgroup analysis by age from the REVERSE-IT trial, which had previously showcased the monoclonal antibody bentracimab (PhaseBio Pharmaceuticals) for its ability to reverse the antiplatelet effects of ticagrelor.

REVERSE-IT is accompanied on the schedule by several secondary-endpoint presentations from trials whose primary outcomes have already been presented at meetings or in the journals.

They include the SCORED trial of sotagliflozin in patients with diabetes and chronic kidney disease (CKD); COMPLETE, which explored complete revascularization of multivessel coronary disease at primary stenting; and the FAME-3 comparison of coronary bypass surgery (CABG) vs. percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) readings.

The session is to conclude with EDIT-CMD, which was a small, randomized assessment of diltiazem for improving microvascular dysfunction in patients with chronic angina despite nonobstructive coronary disease.
 

Sunday, April 3, 8:00 a.m.–9:15 a.m. Joint American College of Cardiology/Journal of the American Medical Association LBCT (II)

The SuperWIN (Supermarket Web Intervention) study tested an innovative strategy for community-based promotion of healthy lifestyle choices: point-of-purchase dietary education for grocery shoppers with an online instructional component, and follow-up to determine whether it influenced future food choices.

“Dietary interventions are notoriously difficult for us to implement, let alone to study scientifically,” Dr. Drachman observed. “So we think that there may be opportunity for dietary interventions to be best implemented at grocery stores where people are doing their shopping for food.”

SuperWIN compared supermarket shoppers with at least one CV risk factor who participated in the education intervention to a nonintervention control group for any changes in their DASH scores. The scores reflected consistency with the venerable DASH diet based on participants’ food purchases over 3 months.

In the same session, the MITIGATE trial explored whether daily administration of icosapent ethyl (Vascepa) might cut the risk of upper respiratory infection (especially from SARS-CoV-2 or seasonal influenza virus) in persons 50 or older with a history of clinical coronary, neurovascular, or peripheral vascular disease or revascularization. The trial has an estimated enrollment of 39,600.

Accompanying SuperWIN and MITIGATE are studies of several dyslipidemia drugs, including the discontinued antisense agent vupanorsen (Pfizer), as tested in TRANSLATE-TIMI 70;  the PCSK9 inhibitor alirocumab (Praluent), explored for its effects on coronary plaque volume and composition in the PACMAN-AMI trial; and the APOLLO trial, a phase 1 evaluation of SLN360 (Silence Therapeutics), a short interfering ribonucleic acid (siRNA) that suppresses the molecular machinery in the liver that produces lipoprotein(a), or Lp(a).

The 32-patient APOLLO trial’s recently released top-line results suggested that SLN360 at varying dosages reduced Lp(a) levels by about one-half to more than 90%. Although elevated Lp(a) is known to track with CV risk, it remains to be shown whether dropping Lp(a) levels pharmacologically is protective.
 

Sunday, April 3, 9:45 a.m.–11:00 a.m. Joint American College of Cardiology/New England Journal of Medicine LBCT (III)

The meeting’s all-HF late-breaker session includes the METEORIC-HF trial, which compared the myotropic agent omecamtiv mecarbil (Cytokinetics) against placebo for effects on exercise performance over 20 weeks. The trial entered 276 patients with HF with reduced ejection fraction (HFrEF) and reduced peak VO₂.

The GALACTIC-HF trial had previously suggested that the drug improved the risk of HF-related events or CV death in more than 8000 patients with HFrEF, those with the lowest ejection fractions benefiting the most.

This block of trials also features DIAMOND, the latest trial with a gemologic name to look at the potassium sequestrant patiromer (Veltassa) for any protection against hyperkalemia, a familiar side effect of renin-angiotensin-aldosterone inhibitors. DIAMOND tested patiromer in 878 patients with HFrEF who were on beta-blockers and other HF-appropriate medications and had a history of drug-associated hyperkalemia.

Previously, the AMBER trial of patients with CKD or refractory hypertension on spironolactone had suggested the drug might be protective enough against hyperkalemia to allow higher and more consistent dosing of BP-lowering agents.

Also in the session: the randomized IVVE (Influenza Vaccine to Prevent Adverse Vascular Events) trial, with an estimated 5,000 patients with HF in Africa, Asia, and the Middle East; PROMPT-HF, with a projected 1,310 HF patients and billed as a cluster-randomized pragmatic trial of a strategy for improving guideline-directed outpatient medical therapy; and MAVA-LTE, the long-term extension study of an estimated 310 patients who were in the MAVERICK-HCM and EXPLORER-HCM mavacamten trials.
 

Sunday, April 3, 12:15–1:30 p.m. Featured Clinical Research II. Main Tent, Hall D

The arrhythmia-centric session includes PARTITA, with its estimated 590 patients with primary- or secondary-prevention implantable cardioverter-defibrillators (ICDs). The trial followed them initially for burden of untreated nonsustained ventricular tachycardia (VT) or events treated with anti-tachycardia pacing. Then it randomly assigned those who experienced a first appropriate ICD shock to either immediate VT ablation or standard care. The latter included ablation on next occurrence of arrhythmic storm.

Investigational oral factor XIa inhibitors, viewed by many as potentially safer as anticoagulants than contemporary oral inhibitors of factor Xa, are now on the scene and include milvexian (Bristol-Myers Squibb/Janssen) and, lately, asundexian (BAY 2433334; Bayer). The latter agent was compared to the factor Xa inhibitor apixaban (Eliquis) in 753 patients with AF in the phase 2 PACIFIC-AF trial, which looked at the newer drug’s safety and optimal dosing.

Also on the bill: a long-term follow-up of the mAFA-2 (Mobile AF Application 2) extension study, which explored the value of a smartphone-based atrial fibrillation (AF) screening app for improving risk of AF-related events; a presentation billed as “Residual Leaks Post Left Atrial Appendage Occlusion”; and one that declares “low rates of guideline-directed care” to be “associated with higher mortality” in patients with pacemakers or ICDs.
 

Monday, April 4, 8:30 a.m.–9:45 a.m. LBCT IV

This session is to open with the PROTECT trial, which sought to determine whether perioperative “aggressive warming” may be cardioprotective in patients with CV risk factors undergoing noncardiac surgery. Its estimated 5,100 patients were randomly assigned to a procedure that achieves normothermia, that is 37° C (98.6° F), vs. standard care in which patients’ core temperature may decline to no further than 35.5° C (95.9° F).

Next on the list are a second POISE-3 comparison of BP-control strategies comparing hypotension avoidance vs. hypertension avoidance in patients undergoing noncardiac surgery; the pivotal CLASP 2 TR trial of patients with symptomatic tricuspid regurgitation on optimal medical therapy with vs. without treatment with the Edwards PASCAL Transcatheter Repair System; and one said to provide “insights from the Corevalve US Pivotal and SURTAVI trials” on 5-year incidence, timing, and predictors of hemodynamic valve deterioration transcatheter and surgical aortic bioprostheses.”

Rounding out the block of presentations: the ADAPT-TAVR comparison of the factor Xa inhibitor edoxaban (Lixiana) to dual-antiplatelet therapy for prevention of leaflet thrombosis after successful transcatheter aortic valve replacement (TAVR). The 235-patient trial was conducted at five centers in South Korea, Hong Kong, and Taiwan.
 

Monday, April 4, 11:00–12:15 p.m. LBCT V

This session includes the FLAVOUR randomized comparison of PCI guided by either FFR or intravascular ultrasound (IVUS) in 1,700 patients with 40%-70% stenoses. The patients from centers in China and South Korea were followed for death from any cause, MI, or any repeat revascularization at 24 months.

Also scheduled: the 2-year report on 4,000 patients with ST-segment elevation MI (STEMI) in the ACC-sponsored quality improvement program GHATI (Global Heart Attack Treatment Initiative); the GIPS-4 myocardial protection study of an estimated 380 patients with STEMI assigned to receive pre- and post-PCI infusions of sodium thiosulfate or placebo, with infarct size at 4 months as the primary endpoint; and a randomized test of an arrhythmia-monitoring implant for influence on clinical outcomes in 802 patients with a history of MI but no pacemaker or ICD indication, called BIO-GUARD-MI,

Last in the session: the Chocolate Touch Study of peripheral-artery angioplasty using a drug-coated balloon (DCB) with a confectionery name that treats lesions not with theobromine, but the antiproliferative mainstay paclitaxel.

The randomized comparison of the Chocolate Touch DCB (TriReme Medical) and the more established Lutonix DCB (Bard) assigned a projected 585 patients with symptomatic peripheral vascular disease to treatment of superficial femoral or popliteal artery lesions with one of the two paclitaxel-coated balloon catheters.
 

Monday, April 4, 12:45–2 p.m. Featured Clinical Research III. Room 143A 

The final session features five subgroup analyses or other updates from trials that have already reported their primary outcomes. Among them is the SPYRAL HTN-ON MED trial, which helped to revitalize hopes for renal denervation therapy as a catheter-based treatment for drug-resistant hypertension by showing significant effects on both systolic and diastolic blood pressure. The new data follow the trial’s more than 400 patients out to 3 years.

There is also a symptom and quality-of-life analysis from the 530-patient EMPULSE trial of 530 patients with stabilized acute HF assigned in-hospital to start on empagliflozin (Jardiance) or placebo. The trial made a splash last year when it reported a significant improvement in risk for death or HF rehospitalization for its patients put on the SGLT2 inhibitor.

A secondary analysis from CANTOS is also featured; the trial had randomly assigned more than 10,000 patients with recent acute MI and elevated C-reactive protein (CRP) levels to receive or not receive the anti-inflammatory canakinumab (Ilaris). Those assigned to active therapy showed benefits for a range of outcomes, including CV mortality and stroke, but no decreases in cholesterol levels. Billing for the new CANTOS analysis promises insights on the “differential impact of residual inflammatory risk and residual cholesterol risk among atherosclerosis patients with and without chronic kidney disease.”

The session also features “trends and final results” from the NACMI (North American COVID-19 Myocardial Infarction) registry, which had shown excellent primary-PCI results without compromise of door-to-balloon times in patients with confirmed SARS-CoV-2 infection; and a FIDELITY analysis of cardiorenal endpoints by history of CV disease in the study’s more than 13,000 patients with diabetes and CKD assigned to placebo or finerenone (Kerendia), a mineralocorticoid receptor antagonist.

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