Tag: intracerebral haemorrhage

Apaxiban no Better than Aspirin for Preventing Recurrence in Cryptogenic Stroke and Atrial Cardiopathy

Trial comparing anticoagulant and antiplatelet therapy ends in a draw

Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0

Administering apaxiban to patients with cryptogenic stroke and evidence of atrial cardiopathy to prevent recurrence was no more effective than giving aspirin, a large randomised trial has found. The trial, published in JAMA, did however find a possible slight advantage in safety of apaxiban over aspirin.

Cryptogenic stroke (CS) is cerebral ischaemia of obscure or unknown origin. One third of ischaemic strokes are cryptogenic. 

Atrial cardiopathy is defined as any complex of structural, architectural, contractile, or electrophysiologic changes affecting the atria with the potential to produce clinically relevant manifestations. Atrial cardiopathy is strongly associated with incident atrial fibrillation and plays a role in thromboembolism related to atrial fibrillation.

Atrial cardiopathy is associated with stroke in the absence of clinically apparent atrial fibrillation. But it was not known whether anticoagulation, which has proven benefit in atrial fibrillation, prevents stroke in patients with atrial cardiopathy and no atrial fibrillation. The Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) trial was therefore designed to determine whether anticoagulation is superior to antiplatelet therapy for preventing recurrent stroke in such patients.

From 2018 to 2023, the researchers conducted a multicentre, double-blind, phase 3 randomised clinical trial of 1015 participants with CS and evidence of atrial cardiopathy – defined as P-wave terminal force greater than 5000μV×ms in electrocardiogram lead V1, serum N-terminal pro-B-type natriuretic peptide level greater than 250pg/mL, or left atrial diameter index of 3cm/m2 or greater on echocardiogram. Participants had no evidence of atrial fibrillation at the time of randomisation.

The participants were randomised 1:1 to receive either apaxiban (5mg or 2.5 mg) twice daily or aspirin (81mg) once daily. The primary outcome measure of stroke occurrence was identical in both arms (40 patients, 4.4%).

There were zero intracranial haemorrhage events for apaxiban vs seven for aspirin, which is known to increase the risk of these. This supports a superior safety profile for apxiban over aspirin, but given the small number of events, the authors caution that this may be a chance finding.

Study limitations included a higher than expected dropout rate due to the COVID pandemic. Additionally, few patients met the atrial cardiopathy criterion of severe left atrial enlargement, but restricting the trial participants to this criterion would have rendered the trial infeasible.

Brain Haemorrhage Risk Factor could be Transmissible via Blood Transfusion

A major study led by researchers at Karolinska Institutet suggests that a possible cause of spontaneous brain haemorrhage could be transmitted via blood transfusion. At the same time, it is very unlikely that anyone should suffer a brain haemorrhage after receiving donated blood, according to the study findings which are published in JAMA.

A common cause of spontaneous, recurring brain haemorrhages is the vascular disease cerebral amyloid angiopathy (CAA), in which proteins accumulate along the small blood vessels of the brain. Several studies have shown that CAA can be transferred from one individual to another through neurosurgery and probably via treatment using a certain type of growth hormone.

Few affected individuals

This new study led by researchers from Karolinska Institutet shows that patients who have received blood from donors who later suffered recurring brain haemorrhages are more than twice as likely to suffer a brain haemorrhage themselves.

The findings suggest that some factor that can give rise to spontaneous brain haemorrhages can be spread through blood transfusion. However, as only 0.1% of the donors in the study subsequently suffered recurring brain haemorrhages there were consequently only a few affected patients.

“Blood transfusions are relatively common, which makes possible negative effects an important public health issue,” says the study’s last author Gustaf Edgren, researcher at the Department of Medicine, Karolinska Institutet (Solna) and specialist physician at Södersjukhuset. “However, in this case, it’s very unlikely that you’d suffer a brain haemorrhage from something transmitted through a transfusion.”

CAA could be transmissible

According to the researchers, the most important implication of the study is instead that it adds further support to the hypothesis that CAA can be transmitted between individuals, which, if true, can have consequences in several fields.

The study drew on the data of more than a million patients the Swedish-Danish transfusion database SCANDAT, which contains data on blood donors and patients receiving a transfusion from the 1970s onwards. The primary analyses were conducted in Sweden and then repeated with the Danish data, with almost identical results.

Confirmation needed

The researchers now hope to corroborate the hypothesis that the link between brain haemorrhage and blood transfusion concerns CAA. They will therefore be examining samples from the Danish Blood Donor Study biobank to see if they can identify aberrant proteins associated with the disease.

The plan is also to obtain CAT and MR scans from the affected donors and patients to see if they might also be able to support the hypothesis.

“This study does not demonstrate causality, so the observed increase in risk could depend on other factors,” says the study’s first author Jingcheng Zhao from Dr Edgren’s group at Karolinska Institutet. “More research is needed to confirm our findings and understand the potential underlying mechanism.”

Source: Karolinska Institutet

New Care Bundle Boosts Intracerebral Haemorrhage Survival and Outcomes

Photo by Alex Fedini on Pixabay

New data from the phase III INTERACT3 study demonstrates that a new combination of treatments for stroke due to intracerebral haemorrhage (ICH) significantly improves the chances of favourable outcomes and reduces deaths by one in every 35 patients. The results are important for low- and middle-income countries like South Africa, as the proportion of ICH is much higher in such countries.

The INTERACT3 study is the first-ever randomised controlled trial to show a clearly positive outcome for the treatment of ICH. Timely administration of the new Care Bundle centred on rapid hypertension control, led to improved recovery, lower rates of death, and better overall quality of life in ICH patients. The findings were presented at the European Stroke Organisation Conference in Munich, Germany, and simultaneously published in The Lancet.

Professor Craig Anderson, Director of Global Brain Health at The George Institute and a senior author of the research said, “Despite the high rates of ICH and its severity, there are few proven options for treating it, but early control of high blood pressure is the most promising. Time is critical when treating this type of stroke, so we tested a combination of interventions to rapidly stabilise the condition of these patients to improve their outcomes. We estimate that if this protocol was universally adopted, it could save tens of thousands of lives each year around the world.”

In the INTERACT3 study, over 7000 patients were enrolled across 144 hospitals in 10 countries – nine middle-income countries and one high-income country. The research team evaluated the effectiveness of the new Care Bundle, which included early intensive lowering of systolic blood pressure, strict glucose control, fever treatment, and rapid reversal of abnormal anticoagulation.

They found that using this new treatment protocol compared to usual care reduced the likelihood of a poor functional outcome, including death, after six months. This was estimated to prevent one additional death for every 35 patients treated.

Central to this was a rapid reduction in systolic blood pressure, where target levels were achieved, on average, in 2.3 hours [range 0.8 to 8.0hrs], compared to 4.0 hours [range 1.9 to 16.0hrs] in the control group. The interventional protocol resulted in a statistically significant reduction in mortality, number of serious adverse events, and time spent in hospital, as well as demonstrating an improvement in health-related quality of life.

 Patients in the care bundle group had fewer serious adverse events than those in the usual care group (16.0% vs 20.1%).

The burden of ICH is greatest in low- and middle-income countries. In 2019, 30% of all stroke cases in LMICs were ICH, almost double the proportion seen in high-income countries (16%). This is in part due to high rates of hypertension and limited resources for primary prevention strategies, including identification and management of stroke risk factors by healthcare services.

Dr Lili Song, joint lead author and Head of the Stroke Program at The George Institute China, said, “A lack of proven treatments for ICH has led to a pessimistic view that not much can be done for these patients. However, with INTERACT3, we demonstrate on a large scale how readily available treatments can be used to improve outcomes in resource-limited settings. We hope this evidence will inform clinical practice guidelines across the globe and help save many lives.”

Source: George Institute for Global Health

Physical Activity may Reduce Bleed Volume of Intracerebral Haemorrhages

Photo by Barbara Olsen on Pexels

Regular physical activity and exercise may reduce bleeding in individuals with intracerebral haemorrhage, a University of Gothenburg study shows. The study, published in the journal Stroke and Vascular Neurology, analysed data on 686 people treated for intracerebral haemorrhage at Sahlgrenska University Hospital in Gothenburg during the years 2014 to 2019.

The study was a retrospective analysis and could not determine causation. Nonetheless, it was clear that those who reported regular physical activity had smaller haemorrhages than those who reported being inactive.

Physically active was defined as engaging in at least light physical activity, such as walking, cycling, swimming, gardening, or dancing, for at least four hours weekly.

50 percent less bleeding volume

The main author of the study is Adam Viktorisson, a PhD student in clinical neuroscience at Sahlgrenska Academy, University of Gothenburg, and doctor in general practice at Sahlgrenska University Hospital.

“We found that individuals who engage in regular physical activity had, on average, bleeding volumes that were 50 percent smaller upon arriving to the hospital. A similar connection has previously been seen in animal studies, but no prior study has demonstrated this in humans.”

Everyone who comes to the hospital with a suspected intracerebral haemorrhage undergoes a computerized tomography (CT) scan of the brain. Depending on the severity of the haemorrhage, neurosurgery may be required. However, in most cases, non-surgical methods and medications are used to manage symptoms and promote patient recovery.

Intracerebral haemorrhage is the most dangerous type of stroke and can lead to life-threatening conditions. The risk of severe consequences from the haemorrhage increases with the extent of the bleeding.

“In cases of major intracerebral haemorrhages, there is a risk of increased pressure within the skull that can potentially lead to fatal outcomes” says Thomas Skoglund, associate professor of neurosurgery at the University of Gothenburg, neurosurgeon at the University Hospital, and one of the study’s co-authors.

Better understanding of intracerebral hemorrhages

The findings were significant regardless of the location within the cerebrum. Physically active individuals exhibited reduced bleeding in both the deep regions of the brain, which are often associated with high blood pressure, and the surface regions, which are linked to age-related conditions like dementia.

The study creates scope for further research on intracerebral haemorrhages and physical activity. Katharina Stibrant Sunnerhagen, professor of rehabilitation medicine at the University of Gothenburg and senior consultant physician at Sahlgrenska University Hospital, oversees the study.

“We hope that our findings contribute to a deeper understanding of intracerebral haemorrhages and aid in the development of more effective preventive measures” she concludes.

Source: University of Gothenburg

Statins Found to Reduce Intracerebral Haemorrhage Risk

Credit: American Heart Association

People taking statins may have a lower risk of having an intracerebral haemorrhage (ICH), according to a new study published in the journal Neurology.

It has been suggested that statins increase the risk of ICH in people with a history of stroke, which has led to a precautionary principle of avoiding statins in patients with prior intracerebral haemorrhage. Recent research suggests that such prescribing reticence may be unfounded and potentially harmful when considering the well-established benefits of statins.

“While statins have been shown to reduce the risk of stroke from blood clots, there has been conflicting research on whether statin use increases or decreases the risk of a person having a first intracerebral haemorrhage,” said study author David Gaist, MD, PhD, of the University of Southern Denmark in Odense. “For our study, we looked at the lobe and non-lobe areas of the brain to see if location was a factor for statin use and the risk of a first intracerebral haemorrhage. We found that those who used a statin had a lower risk of this type of bleeding stroke in both areas of the brain. The risk was even lower with long-term statin use.”

The lobe area of the brain includes most of the cerebrum, including the frontal, parietal, temporal and occipital lobes. The non-lobe area primarily includes the basal ganglia, thalamus, cerebellum and brainstem.

For the study, researchers looked at health records in Denmark and identified 989 people, average age 76, who had an ICH in the lobe area of the brain. They were compared to 39 500 matched controls.

They also looked at 1175 people, average age of 75, who had an ICH in the non-lobe parts of the brain. They were compared to 46 755 matched controls. Prescription data was used to determine information on statin use.

Of the total participants, 6.8% who had a stroke had been taking statins for five or more years, compared to 8.6% of those who did not have a stroke.

After adjusting for factors such as hypertension, diabetes, and alcohol use, researchers found that people currently using statins had a 17% lower risk of having a stroke in the lobe areas of the brain and a 16% lower risk of stroke in the non-lobe areas of the brain.

In addition, longer use of statins was associated with a lower risk of stroke in both areas of the brain. With more than five years of statin use, people had a 33% lower risk of having a stroke in the lobe area of the brain and a 38% lower risk of stroke in the non-lobe area of the brain.

“It’s reassuring news for people taking statins that these medications seem to reduce the risk of bleeding stroke as well as the risk of stroke from blood clots,” Gaist added. “However, our research was done in only the Danish population, which is primarily people of European ancestry. More research should be conducted in other populations.”

Source: American Academy of Neurology

The American Heart Association’s New Intracerebral Haemorrhage Guideline

Credit: American Heart Association

A new guideline published in the journal Stroke reveal that home treatments or preventive therapies used to manage intracerebral haemorrhages (ICH) are not as effective as previously believed.

The guideline from the  American Heart Association/American Stroke Association includes recommendations on surgical techniques, individual activity levels after an ICH, and additional education and training for at-home caregivers. It reflects advances in the intracerebral haemorrhage field since the last guideline on ICH management was published in May 2015.

“Advances have been made in an array of fields related to ICH, including the organisation 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,” said Steven M. Greenberg, M.D., Ph.D., FAHA, chair of the guideline writing group.

Updates to Standard Care Practices

The new guideline suggests that many techniques widely considered “standard care” are unnecessary. For example, wearing compression socks or stockings to prevent deep vein thrombosis after ICH was not found to be effective. Instead, use of intermittent pneumatic compression may be helpful if started on the same day of an ICH diagnosis.

“This is an area where we still have a lot of exploration to do. It is unclear whether even specialised compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed. Even more research is needed on how new blood clot prevention medications may help, especially within the first 24 to 48 hours of the first symptoms,” said Dr Greenberg.

Use of anti-seizure medicines or anti-depressants after ICH is also updated; neither of these classes of medications helps a person’s overall health unless a seizure or depression is already present, therefore, they are not advised for most people. Anti-seizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of anti-depressants increased the chance of bone fractures.

The guideline writing group also addresses previously standard in-hospital therapies. They suggest administering steroids to prevent complications from a bleeding stroke is ineffective and highlight that platelet transfusions, unless used during an emergency surgery, may worsen the stroke survivor’s condition.

Surgical Intervention

Some research suggests procedures with a less invasive approach are less likely to damage brain tissue while removing the fluid build-up.

“The evidence is now reasonably strong that minimally invasive surgery may improve the likelihood that a patient will survive following a moderate or large ICH,” says Greenberg. “It is less clear, however, whether this or any other kind of surgical procedure improves the chances of survival and recovery from ICH, which are our ultimate goals.”

Recovery and Rehabilitation

Stroke rehabilitation includes several strategies to help restore the individual’s quality of life, and the guideline reinforces the importance of having a multi-disciplinary team to develop a plan for recovery. Research suggests a person with a mild or moderate ICH may begin activities like stretching, dressing, bathing and other normal daily tasks 24–48 hours after the stroke to improve survival rate and recovery time; however, moving too much or too intensely within 24 hours is linked to an increased risk of death within 14 days after an ICH.

Home Caregivers

The guideline also recommends education, practical support and training for family members so they may be involved and knowledgeable about what to expect during rehabilitation.

Other Highlights

The guideline suggests there may be an opportunity to prevent ICH in some people by using MRI which can image small blood vessel damage. In addition, major risk factors for small vessel damage are high blood pressure, Type 2 diabetes and older age. Blood thinners remain an important topic since the use of these medications may increase complications and death from a bleeding stroke. Updated guidance is provided for immediate reversal of the newer blood thinners like apixaban, rivaroxaban, edoxaban and dabigatran, as well as older medications like warfarin or heparin.

Renewed emphasis is placed on the complexities of a do-not-attempt-resuscitation (DNAR) status versus the decision to limit other medical and surgical interventions. The writing group highlights the need to educate medical professionals, stroke survivors and/or the individual’s caregiver about the differences. The guideline recommends the severity of a hemorrhage, as measured by the standard scales, not be used as the sole basis for determining life-saving treatments.

Source: American Heart Association