Tag: aspirin

Categories : CancerTags :

Scientists Discover How Aspirin Could Prevent Metastasis in Some Cancers

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Scientists have uncovered the mechanism behind how aspirin could reduce the metastasis of some cancers by stimulating the immune system.

In the study published in Nature, the scientists say that discovering the mechanism will support ongoing clinical trials, and could lead to the targeted use of aspirin to prevent the spread of susceptible types of cancer and the development of more effective drugs to prevent cancer metastasis.

The scientists caution that aspirin can have serious side effects and that trials are underway to establish safety and efficacy.

A reduction in the spread of some cancers

Studies of people with cancer have previously observed that those taking daily low-dose aspirin have a reduction in the spread of some cancers, such as breast, bowel, and prostate cancers, leading to ongoing clinical trials. However, until now it wasn’t known exactly how aspirin could prevent metastases.

In this study, led by researchers at the University of Cambridge, the scientists say their discovery of how aspirin reduces cancer metastasis was serendipitous.

They were investigating the process of metastasis, because, while cancer starts out in one location, 90% of cancer deaths occur when cancer spreads to other parts of the body.

Lung cancer metastasis. Credit: National Cancer Institute

The scientists wanted to better understand how the immune system responds to metastasis. This is because when individual cancer cells break away from their originating tumour and spread to another part of the body, they are particularly vulnerable to immune attack.

An effect on cancer metastasis

The immune system can recognise and kill these lone cancer cells more effectively than cancer cells within larger originating tumours, which have often developed an environment that suppresses the immune system.

The researchers previously screened 810 genes in mice and found 15 that had an effect on cancer metastasis. In particular, they found that mice lacking a gene that produces a protein called ARHGEF1 had less metastasis of various primary cancers to the lungs and liver.

The researchers determined that ARHGEF1 suppresses T cells, which can recognise and kill metastatic cancer cells.

To find a suitable drug, the scientists traced signals in the cell to determine that ARHGEF1 is switched on when T cells are exposed to a clotting factor called thromboxane A2 (TXA2).

This was an unexpected revelation for the scientists, because TXA2 is already well-known and linked to how aspirin works.

Reduces the production of TXA2

TXA2 is produced by platelets; aspirin reduces the production of TXA2, leading to the anti-clotting effects, which underlies its ability to prevent heart attacks and strokes.

This new research found that aspirin prevents cancers from spreading by decreasing TXA2 and releasing T cells from suppression. They used a mouse model of melanoma to show that in mice given aspirin, the frequency of metastases was reduced compared to control mice, and this was dependent on releasing T cells from suppression by TXA2.

Professor Rahul Roychoudhuri, from the University of Cambridge, who led the study, said:

Despite advances in cancer treatment, many patients with early stage cancers receive treatments, such as surgical removal of the tumour, which have the potential to be curative, but later relapse due to the eventual growth of micrometastases – cancer cells that have seeded other parts of the body but remain in a latent state.

Most immunotherapies are developed to treat patients with established metastatic cancer, but when cancer first spreads there’s a unique therapeutic window of opportunity when cancer cells are particularly vulnerable to immune attack.

We hope that therapies that target this window of vulnerability will have tremendous scope in preventing recurrence in patients with early cancer at risk of recurrence.

More accessible globally

Dr Jie Yang, who carried out the research, at the University of Cambridge, said:

It was a Eureka moment when we found TXA2 was the molecular signal that activates this suppressive effect on T cells.

Before this, we had not been aware of the implication of our findings in understanding the anti-metastatic activity of aspirin. It was an entirely unexpected finding which sent us down quite a different path of enquiry than we had anticipated.

Aspirin, or other drugs that could target this pathway, have the potential to be less expensive than antibody-based therapies, and therefore more accessible globally.

In the future, the researchers plan to help the translation of their work into potential clinical practice by collaborating with Professor Ruth Langley, of the MRC Clinical Trials Unit at University College London, who is leading the Add-Aspirin clinical trial, to find out if aspirin can stop or delay early stage cancers from coming back.

Caution on aspirin use

Professor Langley, who was not involved in this study, commented:

This is an important discovery. It will enable us to interpret the results of ongoing clinical trials and work out who is most likely to benefit from aspirin after a cancer diagnosis.

In a small proportion of people, aspirin can cause serious side-effects, including bleeding or stomach ulcers. Therefore, it is important to understand which people with cancer are likely to benefit and always talk to your doctor before starting aspirin.

Source: UK Research and Innovation

Categories : Immune System Obstetrics & GynaecologyTags :

New Treatment for Pregnancy Loss Caused by Specific Autoantibody

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Amongst women who experience recurrent pregnancy loss, around 20% test positive for a specific autoantibody. A Kobe University-led research team now found a treatment using either of two common drugs that drastically increases these women’s chances of carrying to full-term without complications, reporting their findings in Frontiers in Immunology.

Recurrent pregnancy loss is a condition of women who have lost two or more pregnancies for non-obvious reasons. Kobe University obstetrician Tanimura Kenji and his team have previously found that in 20% of these women, they can detect a specific antibody in their blood that targets their own bodies: anti-β2-glycoprotein I/HLA-DR autoantibodies.

Tanimura explains: “There is no known treatment for this particular condition, but the antibodies have a similar target to those that play a role in a different condition that has an established treatment.” Therefore, he wanted to test whether that treatment also works in the cases with the newly discovered antibody.

Tanimura enlisted the help of obstetricians across five hospitals in Japan and over the course of two years analysed the blood of consenting women suffering from recurrent pregnancy loss for the antibodies. If any of these women got pregnant during this time frame, their doctors would offer treatment options also containing those drugs that are effective against the chemically similar condition, specifically, low-dose aspirin or heparin. The research team then observed how many of the women who included these drugs in their treatment had full-term live births or pregnancy complications and compared that to the pregnancy outcomes in women who did not take either of the two drugs.

They report that women who received the treatment were much more likely to have live births (87% did) compared to the ones without treatment (of which only 50% had live births). In addition, amongst the live births, the treatment reduced the likelihood of complications from 50% to 6%. “The sample size was rather small (39 women received the treatment and 8 did not), but the results still clearly show that a treatment with low-dose aspirin or heparin is very effective in preventing pregnancy loss or complications also in women who have these newly discovered self-targeting antibodies,” summarises Tanimura.

Many women who tested positive for the newly discovered self-targeting antibodies also tested positive for the previously known ones. However, the Kobe University-led team found that women who only had the newly discovered antibodies and who received the treatment were even more likely to have a live birth (93%) and, amongst these, none had pregnancy complications.

Looking ahead, Tanimura says: “The newly discovered self-targeting antibody has been demonstrated to be involved also in infertility and recurrent implantation failure, as well as a risk factor for arterial thrombosis in women with systemic rheumatic diseases. I therefore expect that studies about the effectivity of the treatment against a broader range of conditions might produce encouraging results.”

Source: Kobe University

Categories : Obstetrics & GynaecologyTags :

Low-dose Aspirin Might Help Prevent Pregnancy Complications Caused by Flu Infections

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A world-first study has found low-dose aspirin may treat flu-induced blood vessel inflammation, creating better blood flow to the placenta during pregnancy. Animal studies examined whether the treatment for preeclampsia could be applied to flu infections – and the results, published in Frontiers in Immunology, were very promising. 

Lead researcher and RMIT Post-Doctoral Research Fellow, Dr Stella Liong, said that flu infections during pregnancy can resemble preeclampsia, a pregnancy complication that causes inflammation to the aorta and blood vessels. Low-dose aspirin is commonly taken to prevent preeclampsia, as it stops the body from creating chemicals that cause inflammation.   

“When the vascular system is inflamed, it leads to poor blood flow and affects the aorta’s function,” she said. “This is especially a problem during pregnancy where good blood flow to the placenta is crucial to the development of the foetus.” 

The research, led by RMIT University in collaboration with Trinity College Dublin, Ireland Professor John O’Leary and University of South Australia Professor Doug Brooks, found foetuses and placenta from mice with influenza A were smaller than those from uninfected mice. 

Markers of low blood oxygenation and poor blood vessel development were also evident in the foetuses. The mice treated daily with low-dose aspirin had less inflammation and improved foetal development and offspring survival. 

While the research was still awaiting human clinical trials, Liong said low-dose aspirin was already recognised as safe to take during pregnancy. The research team however recommended pregnant people seek medical advice before taking new medications.  

Brooks said influenza A infections during pregnancy was a big concern as every pregnancy overlaps with part of a flu season.  

“There are long term implications for both the mother and the foetus, and aspirin might provide a simple solution for preventing this influenza associated pathology,” Brooks said. 

Why flu infection is dangerous during pregnancy 

O’Leary said the research findings had huge implications for pregnancy and seasonal influenza virus infections for pregnant people.

“This study shines a light, for the first time, on the role of vascular inflammation associated with influenza virus and the potential dramatic effect of the disease-modifying drug aspirin, in low dosage, in pregnant women with co-morbid influenza,” O’Leary said.

While there weren’t many studies of the impacts of flu infections during pregnancy, project lead and RMIT Professor Stavros Selemidis said it was clear that pregnancy changed how the body responded to the virus.

Liong and Selemidis’ earlier breakthrough research found the flu virus during pregnancy could trigger a damaging hyperactive immune response, causing the virus to spread around the body from the lungs through the blood vessels.

“We used to think the flu virus just stayed in the lungs, but during pregnancy it escapes from the lungs to the rest of the body,” Selemidis said.

“This infection could set you up for cardiovascular disease later in life, but also set up cardiovascular disease in the offspring later in life.” 

While vaccination was still the considered the best way to prevent flu infection during pregnancy, Selemidis pointed out vaccination rates were generally low in the pregnant population. 

“Low vaccination rates aside, the flu shot may not generate the perfect immune response, especially if someone is pregnant or has an underlying medical condition,” he said.  

“That’s why it’s useful to have a potential back up in low-dose aspirin to help prevent vascular dysfunction during pregnancy and improve foetal development.”

Source: RMIT University

Categories : Obstetrics & GynaecologyTags :

Low-dose Aspirin Could Help Prevent Pregnancy Complications Caused by Flu Infections

On By ModernMedia
Photo by SHVETS production

A world-first study in animals has found low-dose aspirin may treat flu-induced blood vessel inflammation, creating better blood flow to the placenta during pregnancy. The study, published in Frontiers in Immunology, showed that treatment for preeclampsia could be applied to flu infections – and the results, according to the research team, were very promising. 

Lead researcher and RMIT Post-Doctoral Research Fellow, Dr Stella Liong, said flu infections during pregnancy can resemble preeclampsia, a pregnancy complication that causes inflammation to the aorta and blood vessels.  

Low-dose aspirin is commonly taken to prevent preeclampsia, as it stops the body from creating chemicals that cause inflammation.   

“When the vascular system is inflamed, it leads to poor blood flow and affects the aorta’s function,” she said. 

“This is especially a problem during pregnancy where good blood flow to the placenta is crucial to the development of the foetus.” 

The research, led by RMIT University in collaboration with Trinity College Dublin, Ireland Professor John O’Leary and University of South Australia Professor Doug Brooks, found foetuses and placenta from mice with influenza A were smaller than those from uninfected mice. 

Markers of low oxygen to the blood and poor blood vessel development were also evident in the foetuses. 

However, mice treated daily with low-dose aspirin had less inflammation and improved foetal development and offspring survival. 

While the research was still awaiting human clinical trials, Liong said low-dose aspirin was already recognised as safe to take during pregnancy.  

However, the research team recommended pregnant people seek medical advice before taking new medications.  

Brooks said influenza A infections during pregnancy was a big concern as every pregnancy overlaps with part of a flu season.  

“There are long term implications for both the mother and the foetus, and aspirin might provide a simple solution for preventing this influenza associated pathology,” Brooks said. 

Source: RMIT University

Categories : CancerTags :

Study Explains How Aspirin can Help Prevent Colorectal Cancer Development

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Studies have shown that long-term daily use of aspirin can help to prevent the development and progression of colorectal cancer, but the mechanisms involved have been unclear. New research has revealed that aspirin may exert these protective effects by boosting certain aspects of the body’s immune response against cancer cells. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

To investigate the effects of aspirin (a nonsteroidal anti-inflammatory drug) on colorectal cancer, investigators in Italy obtained tissue samples from 238 patients who underwent surgery for colorectal cancer in 2015–2019, 12% of whom were aspirin users. Patients were enrolled in the METACCRE section of the IMMUNOlogical microenvironment in the REctal Adenocarcinoma Treatment (IMMUNOREACT 8) multicenter observational study. The study was funded by the Associazione Italiana per la Ricerca sul Cancro (AIRC) and was mainly carried out at the University Hospital of Padova.

Compared with tissue samples from patients who did not use aspirin, samples from aspirin users showed less cancer spread to the lymph nodes and higher infiltration of lymphocytes into tumours. In analyses of colorectal cancer cells in the lab, exposing the cells to aspirin caused increased expression of a protein called CD80 on certain immune cells, which enhanced the capacity of the cells to alert other immune cells of the presence of tumour-associated proteins. Supporting this finding, the researchers found that in patients with rectal cancer, aspirin users had higher CD80 expression in healthy rectal tissue, suggesting a pro-immune surveillance effect of aspirin.

“Our study shows a complementary mechanism of cancer prevention or therapy with aspirin besides its classical drug mechanism involving inhibition of inflammation,” said principal investigator Marco Scarpa MD, PhD, of the University of Padova. “Aspirin is absorbed in the colon by passive diffusion to a significant degree. Its absorption is linear and depends on concentration along the bowel, and in the rectum, the concentration of orally administered aspirin can be much lower than in the rest of the colon. Thus, if we want to take advantage of its effects against colorectal cancer, we should think of how to guarantee that aspirin reaches the colorectal tract in adequate doses to be effective.” 

Source: Wiley

Categories : Cardiovascular Disease Surgeries & ProceduresTags :

Stop Aspirin after Stent to Reduce Bleeding in MI Patients, Study Suggests

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Percutaneous coronary intervention.
Percutaneous coronary intervention. Credit: Scientific Animations CC4.0

Withdrawing aspirin one month after percutaneous coronary intervention (PCI) in high-risk heart patients and keeping them on ticagrelor alone safely improves outcomes and reduces major bleeding by more than half when compared to patients taking aspirin and ticagrelor combined (also known as dual antiplatelet therapy or DAPT), which is the current standard of care.

These are the results from the ULTIMATE-DAPT study announced during a late-breaking trial presentation at the American College of Cardiology Scientific Sessions on Sunday, April 7, and published in The Lancet.

This is the first and only trial to test high-risk patients with recent or threatened heart attack (acute coronary artery syndromes, or ACS) taking ticagrelor with a placebo starting one month after PCI, and compare them with ACS patients taking ticagrelor with aspirin over the same period. The significant findings could change the current guidelines for standard of care worldwide.

“Our study has demonstrated that withdrawing aspirin in patients with recent ACS one month after PCI is beneficial by reducing major and minor bleeding through one year by more than 50 percent. Moreover, there was no increase in adverse ischaemic events, meaning continuing aspirin was causing harm without providing any benefit,” says Gregg W. Stone, MD, the study co-chair of ULTIMATE-DAPT, who presented the trial results.

“It is my belief that it’s time to change the guidelines and standard clinical practice such that we no longer treat most ACS patients with dual antiplatelet therapy beyond one month after a successful PCI procedure. Treating these high-risk patients with a single potent platelet inhibitor such as ticagrelor will improve prognosis,” adds Dr Stone.

The study analysed 3400 patients with ACS at 58 centres in four countries between August 2019 and October 2022. All of the patients had undergone PCI, a non-surgical procedure in which interventional cardiologists use a catheter to place stents in the blocked coronary arteries to restore blood flow. The patients were stable one month after PCI and were on ticagrelor and aspirin. Researchers randomised the patients after one month, withdrawing aspirin in 1700 patients and putting them on ticagrelor and a placebo, while leaving the other 1700 patients on ticagrelor and aspirin. All patients were evaluated between 1 and 12 months after the procedure.

During the study period, 35 patients in the ticagrelor-placebo group had a major or minor bleeding event, compared to 78 patients in the ticagrelor-aspirin group, meaning that the incidence of overall bleeding incidents was reduced by 55 percent by withdrawing aspirin. The study also analysed major adverse cardiac and cerebrovascular events including death, heart attack, stroke, bypass graft surgery, or repeat PCI. These events occurred in 61 patients in the ticagrelor-placebo group compared to 63 patients in the ticagrelor-aspirin group, and were not statistically significant – further demonstrating that removing aspirin did no harm and improved outcomes.

“It was previously believed that discontinuing dual antiplatelet therapy within one year after PCI in patients with ACS would increase the risk of heart attack and other ischaemic complications, but the present study shows that is not the case, with contemporary drug-eluting stents now used in all PCI procedures. Discontinuing aspirin in patients with a recent or threatened heart attack who are stable one month after PCI is safe and, by decreasing serious bleeding, improves outcomes,” Dr Stone adds. “This study extends the results of prior work that showed similar results but without the quality of using a placebo, which eliminates bias from the study.”

Source: The Mount Sinai Hospital / Mount Sinai School of Medicine

Categories : Cardiovascular DiseaseTags :

Heart Disease Research Challenges ‘One Size Fits All’ Aspirin Guidelines

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Analysis of results from international trials question whether current aspirin recommendations apply to all patients

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Heart disease researchers have identified a group of patients in whom international guidelines on aspirin use for heart health may not apply. In a study published in the medical journal Circulation, the findings of a review of data from three clinical trials challenge current best practice for use of the drug for primary prevention of heart disease or stroke – otherwise known as atherosclerotic cardiovascular disease.

The research examined the results from clinical trials involving more than 47 000 patients in 10 countries, including the US, the UK and Australia, which were published in 2018.

The analysis focused on findings for a subgroup of 7222 patients who were already taking aspirin before the three trials commenced. Those studied were at increased risk for cardiovascular disease and were taking aspirin to prevent the first occurrence of a heart attack or stroke.

The data showed a higher risk of heart disease or stroke – 12.5% versus 10.4% – for patients who were on aspirin before the trials and who then stopped, compared to those who stayed on the drug.

Analyses also found no significant statistical difference in the risk for major bleeding between the two groups of patients.

The research was led by Professor J. William McEvoy, Established Professor of Preventive Cardiology at University of Galway and Consultant Cardiologist at Saolta University Health Care Group, in collaboration with researchers in University of Tasmania and Monash University, Melbourne.

Professor McEvoy said: “We challenged the notion that aspirin discontinuation is a one-size-fits-all approach.”

The research team noted results from observational studies which suggest a 28% higher risk of heart disease or stroke among adults who were prescribed aspirin to reduce the risk for a first heart attack or stroke, but who subsequently chose to stop taking the aspirin without being told to do so by their doctor.

Based in large part on three major clinical trials published in 2018, international guidelines no longer recommend the routine use of aspirin to prevent the first occurrence of heart attack or stroke.

Importantly, aspirin remains recommended for high-risk adults who have already had a heart disease or stroke event, to reduce the risk of a second event.

The move away from primary prevention aspirin in recent guidelines is motivated by the increased risk of major bleeding seen with this common medication in the three trials, albeit major bleeding is relatively uncommon on aspirin and was most obvious only among trial participants who were started on aspirin during the trial, rather than those who were previously taking aspirin safely.

These trials primarily tested the effect of starting aspirin among adults who have not previously been treated with the drug to reduce the risk of atherosclerotic cardiovascular disease. Less is known about what to do in the common scenario of adults who are already safely taking aspirin for primary prevention.

Professor McEvoy said: “Our findings of the benefit of aspirin in reducing heart disease or stroke without an excess risk of bleeding in some patients could be due to the fact that adults already taking aspirin without a prior bleeding problem are inherently lower risk for a future bleeding problem from the medication. Therefore, they seem to get more of the benefits of aspirin with less of the risks.

“These results are hypothesis-generating, but at present are the best available data. Until further evidence becomes available, it seems reasonable that persons already safely treated with low-dose aspirin for primary prevention may continue to do so, unless new risk factors for aspirin-related bleeding develop.”

Source: University of Galway

Categories : Cardiovascular DiseaseTags :

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

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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.

Categories : Cardiovascular Disease Implants and ProsthesesTags :

No-aspirin Regimen Benefits Heart Failure Patients with LVADs

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A recent clinical trial published in JAMA found that excluding aspirin for advanced heart failure (HF) patients with a ventricular assist device saw a reduction in bleeding events while maintaining their survival rates.

The ARIES-HM3 Randomised Clinical Trial assessed the safety and efficacy of excluding aspirin from the antithrombotic regimen in patients with advanced HF who have undergone implantation of a fully magnetically levitated left ventricular assist device (LVAD).

“We can now safely say that not giving aspirin is not only safe from a thromboembolic risk profile but results in improved adverse event rate by a significant reduction in non-surgical bleeding which is a well-known complication related to LVAD therapy,” said Mirnela Byku, MD, P.D, MBA, co-author of the study and director of the UNC Durable Mechanical Circulatory Device Program at the UNC School of Medicine.

“Improving not only longevity but also reducing morbidity and improving quality of life is a big focus in the field of MCS.”

Until this study, there had been no consensus in the field about use of or dose of aspirin in the LVAD population.

The international clinical trial followed a randomised, double-blind, placebo-controlled design and involved 628 patients across 51 centres in 9 countries.

The patients were divided into two groups: one receiving aspirin (100mg/d) and the other receiving a placebo in addition to vitamin K antagonist (VKA) therapy.

A focus was to determine if the likelihood a patient experiences major nonsurgical haemocompatibility-related adverse events (such as stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) within 12 months differed between the two groups.

The results showed that not giving aspirin to patients with advanced HF, treated with a fully magnetically levitated LVAD who are receiving VKAs, did not make their survival worse. Furthermore, aspirin avoidance was associated with a significant reduction (34%) in major nonsurgical bleeding events.

Source: University of North Carolina Health Care

Categories : Ageing Cardiovascular DiseaseTags :

Rethink Preventative Aspirin for Older Adults, Researchers Say

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Low-dose aspirin is used as primary prevention for ischaemic stroke, but its protective effect weighed against the increased risk of bleeding events is controversial. A new secondary analysis of daily aspirin in older people found that, in this population, aspirin failed to reduce the risk for ischaemic stroke but increased it for intracranial bleeding. The findings were presented in JAMA Network Open.

The researchers analysed data from the ASPREE randomised clinical trial, the first large-scale trial to study the risks and benefits of 100mg daily aspirin in an older population, where increased bleeding risk may alter the balance of risks and benefits of aspirin. This is particularly relevant to intracerebral events because intracranial haemorrhage is harder to treat than ischaemic events and more frequently fatal or disabling. With previous aspirin trials in mostly younger participants, excess intracerebral haemorrhagic events was seen, though usually few in number and non-significant.

Cloud et al. performed a secondary analysis of the ASPREE trial, which included 19 114 older adults, and found a statistically significant 38% increase in intracranial bleeding resulting from a combination of haemorrhagic stroke and other causes of intracerebral haemorrhage among individuals randomised to aspirin. The difference in incidence of ischaemic stroke was not statistically significant.

While aspirin did not cause a statistically significant reduction in ischaemic stroke (hazard ratio [HR], 0.89), there was a a statistically significant 38% increase in intracranial bleeding. Rates of intracranial bleeding from those assigned to aspirin (1.1%) were higher than placebo (0.8%). This came from an increase in a combination of subdural, extradural, and subarachnoid bleeding with aspirin (0.6%) compared with placebo (0.4%). Haemorrhagic stroke was recorded in 0.5% of those assigned to aspirin compared with 0.4% for placebo.

Absolute numbers of haemorrhagic and non-haemorrhagic events were small. Among 1000 individuals taking 100mg/day of low-dose aspirin over five years, there were 2.5 fewer ischaemic strokes at the expense of 3.5 cases of intracranial haemorrhage, but not statistically significant. No difference would be expected for overall stroke incidence or stroke mortality, but haemorrhagic stroke was associated with a mortality rate of nearly a third, compared to 7.7% for ischaemic stroke. Major extracranial haemorrhage was driven by the increased risk of upper gastrointestinal bleeding with aspirin compared with placebo, as previously found (Hazard Ratio, 1.87).

The researchers concluded that “there was no statistically significant benefit from aspirin in preventing stroke or any conventional stroke etiological subtype. However, aspirin significantly increased the overall risk of intracranial bleeding.”