Tag: warfarin

Categories : AgeingTags : Leave a comment

Older Patients can Inadvertently be Put at Risk When Taken off Anticoagulants

On By ModernMedia
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For patients with atrial fibrillation, the risk of stroke or heart attack from stopping anticoagulants usually outweighs the risk of bleeding, according to new findings from the University of Bath.

Clinicians often worry about the dangers of prescribing blood thinning medications to older patients, due to concerns about falls and major bleeding, however this new study suggests that for patients with the common heart condition atrial fibrillation (AF), the health risks of not taking these drugs are significantly higher than the risk of a life-threatening bleed.

AF is associated with a fivefold increase in the risk of stroke. It also increases the risk of heart attacks and death. Anticoagulants are highly effective in managing AF and preventing strokes and other complications.

Older people also tend to fall more frequently, with falls being a leading cause of injury among adults aged 65 and older. These can lead to serious injuries, such as hip fractures and head injuries.

However, the new study, published in Heart, found that contrary to popular medical belief, stopping anticoagulants for patients aged 75 and over does not change the risk of major bleeds. These findings are important for clinicians to factor into their prescribing behaviour, according to the study’s authors.

“Prescribers need to consider the increased risk to patients of coming off anticoagulants, including stroke,” said Dr Anneka Mitchell, who conducted the research from the University of Bath and is a visiting researcher at the University’s Department of Life Sciences.

Rising cases

Cases of AF are rising in all age groups but particularly among people aged 85 years and over. In this age group, the number of people diagnosed with the condition doubled in men from 11.6% to 22.1% between 2000 and 2016, and increased in women from 9.6% to 16.5%. There is no data available to show trends from 2016.

Though there is a large body of evidence to support the use of blood thinners for older people with AF, the new study is believed to be the first to measure patient outcomes when anticoagulant medication is stopped.

Dr Mitchell’s study analysed data from the UK Clinical Practice Research Datalink (a research dataset that includes anonymised patient data from some UK general practices) between 2013 and 2017, focusing on patients aged 75 and older who were newly prescribed anticoagulants.

It found that the risks of stroke and death were three times higher during periods when patients were not receiving anticoagulation therapy. The risk of heart attacks was nearly double compared with periods when patients were treated with anticoagulants.

Warfarin versus direct oral anticoagulants

Dr Mitchell believes that as well as concern about falls, many clinicians base their decisions to withhold anticoagulants on the historic experience of patients taking the anticoagulant warfarin.

This medication – the only available option for treating AF until 2012 – is associated with a complex medication regimen, along with dietary restrictions and frequent blood-tests, making treatment difficult for many older patients.

Since 2013, however, a new family of drugs called direct oral anticoagulants (DOACs) have become the first line option for most patients. DOACs are as effective and safe as warfarin – sometimes more so – and are far more straightforward to take.

Dr Mitchell said: “For example, apixaban (a DOAC) has a lower risk of significant bleeding than warfarin, so for many older patients with AF, this would be an excellent medication.

“Our findings highlight the critical need for clinicians to carefully consider the risks of stopping anticoagulation therapy in older patients. Despite concerns about bleeding, this study suggests that discontinuing anticoagulation does not significantly affect the risk of major bleeding but does increase the risk of serious events such as stroke and death.”

She added: “Both the risks and benefits of medication must be discussed fully with patients before a medic stops prescribing anticoagulants, so that both doctor and patient are making a shared and informed decision. This study underscores the importance of evaluating the consequences of deprescribing anticoagulants, particularly in older adults who are at higher risk of adverse outcomes.”

Impacting the lives of older patients

Dr Anita McGrogan who led the research team from the Department of Life Sciences at Bath, said: “Older patients were poorly represented in clinical trials that evaluated the efficacy and safety of DOACs before these products were licensed, and those who were included were healthier than many people in the target group for prescribing. Because of this, the safety of these medications for people aged 75-plus was not evaluated, and many chose to avoid prescribing them for older people.

“This study has produced important results that will have an impact on patients in the future. It has filled the information gap by looking at anonymous data on 20 167 people aged over 75 years, collected by GPs. It clearly demonstrates the value of using big data to investigate important clinical questions, especially in vulnerable populations.”

Dr Tomas Welsh, an academic geriatrician at Royal United Hospitals Bath and research & medical director at ReMind, hopes the new research will provide both clinicians and patients with better evidence to inform their decisions regarding anticoagulants. He noted that, until now, clinicians advising patients to stop taking blood thinners were unable to quantify the increased risk of stroke.

“These data help patients and clinicians have a firmer grasp of the risks that they are being exposed to,” he said.

Dr Welsh also stressed that new-generation blood thinners were not always the right course of action for frail, older people.

“Suspending any medication or reducing the use of multiple medications in a frailer older patient is always a nuanced and individual discussion,” he said.

Source: University of Bath

Categories : Lab Tests and ImagingTags :

Experimental Model Identifies New Drug–drug Interactions

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Photo by Myriam Zilles on Unsplash

When taking oral drugs, transporter proteins found on cells that line the gastrointestinal tract facilitate their entry into the bloodstream. But for many drugs, it is not known which of those transporters they use to exit the digestive tract.

Identifying the transporters used by specific drugs could help to improve patient treatment because if two drugs rely on the same transporter, they can interfere with each other and should not be prescribed together.

Researchers at MIT, Brigham and Women’s Hospital, and Duke University have developed a multipronged strategy to identify the transporters used by different drugs, which appears in Nature Biomedical Engineering. Their approach, which makes use of both tissue models and machine-learning algorithms, has already revealed that a commonly prescribed antibiotic and a blood thinner can interfere with each other.

“One of the challenges in modelling absorption is that drugs are subject to different transporters. This study is all about how we can model those interactions, which could help us make drugs safer and more efficacious, and predict potential toxicities that may have been difficult to predict until now,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study.

Learning more about which transporters help drugs pass through the digestive tract could also help drug developers improve the absorbability of new drugs by adding excipients that enhance their interactions with transporters.

Former MIT postdocs Yunhua Shi and Daniel Reker are the lead authors of the study.

Drug transport

Previous studies have identified several transporters in the GI tract that help drugs pass through the intestinal lining. Three of the most commonly used, which were the focus of the new study, are BCRP, MRP2, and PgP.

For this study, Traverso and his colleagues adapted a tissue model they had developed in 2020 to measure a given drug’s absorbability. This experimental setup, based on pig intestinal tissue grown in the laboratory, can be used to systematically expose tissue to different drug formulations and measure how well they are absorbed.

To study the role of individual transporters within the tissue, the researchers used short strands of RNA called siRNA to knock down the expression of each transporter. In each section of tissue, they knocked down different combinations of transporters, which enabled them to study how each transporter interacts with many different drugs.

“There are a few roads that drugs can take through tissue, but you don’t know which road. We can close the roads separately to figure out, if we close this road, does the drug still go through? If the answer is yes, then it’s not using that road,” Traverso says.

The researchers tested 23 commonly used drugs using this system, allowing them to identify transporters used by each of those drugs. Then, they trained a machine-learning model on that data, as well as data from several drug databases. The model learned to make predictions of which drugs would interact with which transporters, based on similarities between the chemical structures of the drugs.

Using this model, the researchers analysed a new set of 28 currently used drugs, as well as 1595 experimental drugs. This screen yielded nearly 2 million predictions of potential drug interactions. Among them was the prediction that doxycycline, an antibiotic, could interact with warfarin, a commonly prescribed blood-thinner. Doxycycline was also predicted to interact with digoxin, which is used to treat heart failure, levetiracetam, an antiseizure medication, and tacrolimus, an immunosuppressant.

Identifying interactions

To test those predictions, the researchers looked at data from about 50 patients who had been taking one of those three drugs when they were prescribed doxycycline. This data, which came from a patient database at Massachusetts General Hospital and Brigham and Women’s Hospital, showed that when doxycycline was given to patients already taking warfarin, the level of warfarin in the patients’ bloodstream went up, then went back down again after they stopped taking doxycycline.

That data also confirmed the model’s predictions that the absorption of doxycycline is affected by digoxin, levetiracetam, and tacrolimus. Only one of those drugs, tacrolimus, had been previously suspected to interact with doxycycline.

“These are drugs that are commonly used, and we are the first to predict this interaction using this accelerated in silico and in vitro model,” Traverso says. “This kind of approach gives you the ability to understand the potential safety implications of giving these drugs together.”

Source: Massachusetts Institute of Technology

Categories : Cardiovascular DiseaseTags :

With Warfarin, Dropping Aspirin Reduces Bleeding Complications for Some

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Red blood cells
Source: Pixabay

Research from Michigan Medicine suggests that, for venous thromboembolism (VTE) or atrial fibrillation (AF) patients without a history of heart disease who are taking warfarin, stopping aspirin use causes their risk of bleeding complications to drop significantly.

For the study, which is published in JAMA Network Open, researchers analysed over 6700 people treated at anticoagulation clinics across Michigan for VTE as well as AF. Patients were treated with warfarin but also took aspirin despite not having history of heart disease.

“We know that aspirin is not a panacea drug as it was once thought to be and can in fact lead to more bleeding events in some of these patients, so we worked with the clinics to reduce aspirin use among patients for whom it might not be necessary,” said senior study author and cardiologist Geoffrey Barnes, MD.

Over the course of the study, aspirin use among patients fell by 46.6%. With aspirin used less commonly, the risk of a bleeding complication dropped by 32.3% – equivalent to preventing one major bleeding event per every 1000 patients who stop taking aspirin.

“When we started this study, there was already an effort by doctors to reduce aspirin use, and our findings show that accelerating that reduction prevents serious bleeding complications which, in turn, can be lifesaving for patients,” said Dr Barnes. “It’s really important for physicians and health systems to be more cognisant about when patients on a blood thinner should and should not be using aspirin.”

Several studies had found concerning links between concurrent use of aspirin and different blood thinners, which prompted this aspirin de-escalation.

One study reported that patients taking warfarin and aspirin for AF and VTE experienced more major bleeding events and had more ER visits for bleeding than those taking warfarin alone. Similar results were seen for patients taking aspirin and direct oral anticoagulants – who were found more likely to have a bleeding event but not less likely to have a blood clot.

“While aspirin is an incredibly important medicine, it has a less widely used role than it did a decade ago,” Dr Barnes said. “But with each study, we are seeing that there are far fewer cases in which patients who are already on an anticoagulant are seeing benefit by adding aspirin on top of that treatment. The blood thinner they are taking is already providing some protection from clots forming.”

For some people, aspirin can be lifesaving. Many patients who have a history of ischaemic stroke, heart attack or a stent placed in the heart to improve blood flow — as well as those with a history of cardiovascular disease — benefit from the medication.

The challenge comes when some people take aspirin without a history of cardiovascular disease and are also prescribed an anticoagulant, said first author Jordan Schaefer, MD.

“Many of these people were likely taking aspirin for primary prevention of heart attack or stroke, which we now know is less effective than once believed, and no one took them off of it when they started warfarin,” Dr Schaefer said. “These findings show how important it is to only take aspirin under the direction of your doctor and not to start taking over-the-counter medicines like aspirin until you review with your care team if the expected benefit outweighs the risk.”

Source: Michigan Medicine – University of Michigan

Categories : Diseases, Syndromes and ConditionsTags :

Apaxiban is an Option in Severe Renal Dysfunction

On By ModernMedia
Photo by Robina Weermeijer on Unsplash

The anticoagulation options for patients with concomitant renal impairment are limited and until recently, warfarin was the only recommended option due to insufficient data supporting alternative drugs in such patients. A new study published in Blood Advances suggests that apixaban is a viable option in patients with severe renal dysfunction.

Apixaban in patients with impaired renal function is supported by limited data. Landmark clinical trials evaluating apixaban in patients with atrial fibrillation and/or acute venous thromboembolism excluded patients with creatinine clearance (CrCl) <25 mL/min. 

A multicentre, retrospective chart review was conducted to evaluate the safety and effectiveness of apixaban compared with warfarin in patients with CrCl <25 mL/min. Included patients were newly initiated on apixaban or warfarin for at least 45 days with a CrCl <25 mL/min.


Patients were evaluated for thrombosis and bleeding outcomes six  months following initiation of anticoagulation. The primary outcome was the time to first bleeding or thrombosis event. A total of 128 patients met inclusion criteria in the apixaban group and 733 patients in the warfarin group. 

Time to first bleeding or thrombosis event was significantly different between the apixaban and warfarin groups. After controlling for atrial fibrillation and coronary artery bypass grafting, risk of thrombotic and bleeding events was lower in the apixaban group (hazard ratio 0.47). There was no statistical difference between time to thrombosis (83 days vs 54 days, P = .648), rate of thrombosis (5.5% vs 10.3%, P = .08), time to bleeding (46 days vs 54 days, P = .886), or rate of bleeding (5.5% vs 10.9%, P = .06). The severity of bleeding and thrombotic events was not different between groups. 

The results suggest apixaban may be a reasonable option for patients with severe renal dysfunction despite the known increase in apixaban exposure, the researchers concluded. They add that, “These results add to the growing body of evidence of real-world data that apixaban is a reasonable option for patients with severe renal dysfunction.”

The researchers recommend investigating the use of apixaban in patients with a severe renal dysfunction, especially those on haemodialysis, in order to definitively determine the role of apixaban in this patient population.

Source: Blood Advances