In a study of adults with advanced prostate cancer taking androgen-receptor pathway inhibitors and different types of anticoagulants, investigators found no evidence of an increase in patients’ bleeding or clotting risks, despite previous lab results that raised alarms. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.
Thromboembolism, caused by a circulating blood clot that gets stuck and causes an obstruction, is the second leading cause of death in people with cancer, surpassed only by progression of the cancer itself. Anticoagulants (blood thinners) are standard therapy to treat or prevent thromboembolism. For individuals with advanced prostate cancer, thromboembolism can be especially worrisome because lab experiments have indicated that androgen-receptor pathway inhibitors, which are recommended for nearly all patients with advanced prostate cancer, can interact with certain anticoagulants – specifically, direct oral anticoagulants (DOACs).
To investigate whether these lab-based findings correlate to real concerns in patients, researchers evaluated outcomes in patients taking both anticoagulants and androgen-receptor pathway inhibitors, including enzalutamide, apalutamide, and abiraterone.
In the retrospective population-based analysis of 2997 Canadian adults with prostate cancer who were prescribed anticoagulants (DOACs or non-DOACs) and enzalutamide or apalutamide between 2012 and 2023, investigators found no increased risks of clotting in the DOAC versus non-DOAC groups. Similarly, investigators compared DOAC and non-DOAC groups combined with abiraterone and did not find an increased risk of bleeding.
“As clinicians, we are faced with the question of choosing the best anticoagulant option for patients on a daily basis, and the complexity further increases in patients with cancer taking many other medications including anticancer therapies that could cause concerning drug–drug interactions,” said lead author Tzu-Fei Wang, MD, of the University of Ottawa at The Ottawa Hospital and the Ottawa Hospital Research Institute. “Our findings suggest that pharmacokinetic drug–drug interaction concerns may not translate into adverse clinical outcomes in the real world. These results can help clinicians and patients feel more confident when managing anticoagulation alongside modern prostate cancer treatments.”
For older people with irregular heart rhythms who are at high risk of stroke and bleeding, standard care (including the use of blood thinners when indicated) was found to be the better choice compared to a promising, catheter-based procedure, according to a preliminary late-breaking science presentation today at the American Heart Association’s Scientific Sessions 2025.
The trial, Left Atrial Appendage CLOSURE in Patients with Atrial Fibrillation at High Risk of Stroke and Bleeding Compared to Medical Therapy (CLOSURE-AF), compared a catheter-based procedure to medical therapy among patients with atrial fibrillation (AFib), an irregular heart rhythm.
While blood thinners can be highly effective at reducing the risk of stroke among people with AFib, the medication may cause severe bleeding in some people. Due to this risk, researchers are exploring alternative treatments including this catheter-based procedure. The procedure, called a left atrial appendage closure, seals a small pouch in the heart called the left atrial appendage, or LAA, where blood clots can form. If these blood clots enter the bloodstream, it increases the risk of stroke. Closing this pouch reduces the risk of stroke. It also can allow people to stop taking blood thinners for clot prevention.
The CLOSURE AF study compared catheter-based left atrial appendage closure with physician-directed standard medical care (including timely anticoagulant blood thinning when eligible) in patients with atrial fibrillation at high risk for stroke and bleeding. The aim of the study was to demonstrate non-inferiority for catheter-based LAA closure regarding risk of stroke, systemic embolism, cardiovascular/unexplained death or major bleeding. However, this was not reached.
“We expected that catheter-based LAA closure would be comparable to physician-directed standard medical care often using blood thinning anticoagulant medications,” said study lead researcher Ulf Landmesser, MD, chairman of the department of cardiology, angiology and intensive care medicine at Deutsche Herzzentrum Charité and professor of cardiology at Charité University Medicine in Berlin. “However, this was not the case in this trial of older patients at very high risk of bleeding and stroke.
“Our findings indicate that standard physician-directed medical care, including blood thinners for eligible patients, remains a valid management option for those older patients with irregular heartbeat who are at very high risk for stroke and bleeding.”
Landmesser said that the results of the procedure are different for lower-risk patients, and studies investigating this are currently underway. Moreover, ongoing studies are comparing LAA closure in addition to blood thinning in very high-risk patients.
Because medical treatments and LAA closure for AFib remain in development the results of this study may not apply to future research, other techniques or procedures.
Study details, background and design:
More than 900 adults with AFib who were at high risk of stroke and major bleeding participated in this study.
Participants’ average age was 78 years, and 39% were women.
They were enrolled at 42 health care sites in Germany from March 2018 to April 2024, and they were followed for a median of 3 years.
Participants were randomly assigned to one of two treatment groups: standard medical care (including anticoagulant blood thinners, if eligible); or LAA closure.
Researchers compared the frequency of stroke, life-threatening blood clots, cardiovascular/unexplained death and major bleeding between the two treatment groups.
Disposable syringe of Clexane (enoxaparin), a low molecular weight heparin (LMWH). CC0
Researchers at McMaster University have discovered that a rare but dangerous reaction to heparin is caused by a single antibody – overturning decades of medical misunderstanding and opening the door to more precise ways of diagnosing and treating this medical complication.
The study, published in the New England Journal of Medicine, focused on heparin-induced thrombocytopenia (HIT), a serious immune complication that affects approximately one per cent of hospitalised patients treated with the blood thinner heparin. Nearly half of those who develop HIT experience life-threatening blood clots, which can lead to strokes, heart attacks, amputations, and even death, making early detection and treatment critically important.
Until now, scientists believed that the immune response causing HIT involved many different types of antibodies working together. But this research has revealed something surprising: in every patient studied, only one antibody was causing the disease, while the rest created what the researchers describe as a kind of “smokescreen,” making it harder to identify the true culprit. This discovery helps pinpoint the exact source of the problem, opening the door to more accurate diagnosis and better-targeted treatments.
“This study not only challenges our existing understanding of HIT but also revolutionises how we think about the immune response overall,” said Ishac Nazy, senior author of the study and scientific director of the McMaster Platelet Immunology Laboratory and co-director of the Michael G. DeGroote Center for Transfusion Research (MCTR).
“This work corrects decades of misunderstanding in HIT. This status quo was a key reason behind the high rate of false-positive test results and frequent misdiagnoses in HIT, which can lead to severe consequences for patients, including unnecessary treatment or avoidable complications. Our findings lay the groundwork for more accurate diagnostics and targeted treatments,” said Nazy, a professor in the Department of Medicine and the Department of Biochemistry and Biomedical Sciences at McMaster.
The research team was comprised of scientists from the McMaster Platelet Immunology Laboratory (MPIL) within MCTR as well as collaborators from the University of Massachusetts Amherst.
They analysed blood samples from nine patients diagnosed with HIT. In each case, they found that the antibodies targeting platelet factor 4 (PF4) – a protein involved in blood clotting – were monoclonal. This suggests that HIT may be driven by a highly specific immune reaction, rather than a generalised one.
“This discovery could reshape how we diagnose HIT and eventually how we treat it,” said Jared Treverton, first author of the study and a PhD candidate at McMaster. “Knowing that HIT is caused by a monoclonal antibody will allow us to develop improved tests specific to patients with this disorder and design better targeted therapies. This is a major step towards making diagnostics more accurate and treatments much safer.”
The findings are expected to have immediate relevance for haematologists, laboratory specialists, and researchers in immunology, as well as for patients receiving heparin in hospitals across Canada and around the world.
Ischaemic and haemorrhagic stroke. Credit: Scientific Animations CC4.0
Patients with atrial fibrillation who have experienced a stroke would benefit greatly from earlier treatment than is currently recommended in UK guidelines, finds a new study led by UCL researchers.
The results of the CATALYST study, published in The Lancet, included data from four randomised trials with a total of 5441 patients across the UK, Switzerland, Sweden and the United States, who had all experienced a recent stroke (between 2017-2024) due to a blocked artery and atrial fibrillation (irregular heartbeat).
Patients had either started medication early (within four days of their stroke) or later (after five days or more).
The researchers found that starting direct oral anticoagulants (DOACs, which thin the blood to prevent it from clotting as quickly) within four days of having a stroke was safe, with no increase in bleeding into the brain. Additionally, early initiation of treatment significantly reduced the risk of another stroke due to bleeding or artery blockage by 30% compared to those who started treatment later.
People with atrial fibrillation who have had a stroke have an increased risk of having another stroke, but this risk can be reduced by taking anticoagulants.
Anticoagulants come with the rare but dangerous side effect of bleeding into the brain, and there is a lack of evidence about when is best to start taking them after a stroke. Current UK guidelines are varied, suggesting that those who have had a moderate or severe stroke should wait at least five days before starting blood-thinning treatments.
To tackle this question, the researchers investigated the impact of early compared to delayed anticoagulant treatment.
Chief Investigator, Professor David Werring (UCL Queen Square Institute of Neurology) said: “Our new study supports the early initiation of DOACs in clinical practice, offering better protection against further strokes for a wide range of patients.”
The researchers now hope that their findings will influence clinical guidelines and improve outcomes for stroke patients worldwide.
First author and main statistician, Dr Hakim-Moulay Dehbi (UCL Comprehensive Clinical Trials Unit), said: “By systematically combining the data from four clinical trials, we have identified with increased confidence, compared to the individual trials, that early DOAC initiation is effective.”
The CATALYST study builds on findings from the British Heart Foundation funded OPTIMAS study – where the UCL-led research team analysed 3621 patients with atrial fibrillation who had had a stroke between 2019 and 2024, across 100 UK hospitals.
Half of the participants began anticoagulant treatment within four days of their stroke (early), and the other half started treatment seven to 14 days after having a stroke (delayed). Patients were followed up after 90 days to assess several outcomes including whether they went on to have another stroke and whether they experienced bleeding in the brain.
Both the early and late groups experienced a similar number of recurrent strokes. Early treatment was found to be effective and did not increase the risk of a bleed into the brain.
Professor Nick Freemantle, Senior Investigator and Director of the UCL Comprehensive Clinical Trials Unit (CCTU) that co-ordinated the OPTIMAS trial, said: “The benefits of early initiation of blood-thinning treatment are clear: patients receive the definitive and effective long-term stroke prevention therapy promptly, rather than waiting. This approach ensures that crucial treatments are not delayed or missed, particularly for patients who are discharged from the hospital.”
Study limitations
The timing for starting blood-thinning medication was based on previous trial designs (such as OPTIMAS), which may not cover all possible scenarios. Additionally, not all participants were randomised to the same timing groups, so some data was excluded. Lastly, the study didn’t include many patients with very severe strokes, so the findings might not apply to those cases.
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.
Direct oral anticoagulant (DOACs), such as rivaroxaban and apixaban, are under- or over-prescribed in up to one in eight patents, finds a new study. These prescribing issues can have life threatening consequences, and they most often occur after a provider writes the initial prescription, according to a Michigan Medicine-led study in Thrombosis and Haemostasis.
“Direct oral anticoagulants may be viewed as simpler to manage than traditional blood thinners, like warfarin, but our results highlight why providers need to be consistently monitoring anticoagulant medications before a patient experiences thrombotic or bleeding harms,” said Geoffrey Barnes, MD, MSc, senior author and associate professor of cardiology-internal medicine at U-M Medical School.
At hospitals across Michigan, off-label dosing of DOACs was relatively common among patients being treated for atrial fibrillation and venous thromboembolism, when blood clots form in the veins.
Researchers evaluated five years of prescribing data from 2018–2022 through the Michigan Anticoagulant Improvement Initiative, a statewide quality improvement collaborative funded by Blue Cross Blue Shield and Blue Care Network of Michigan.
Nearly 70% of the alerts to off-label dosing occurred during a follow up visit compared to the time of the initial prescription, according to the study results
When prescribers were contacted about the dosing issue, they made changes three-quarters of the time.
However, only 18% of dosing alerts resulted in contact to a prescriber.
“While many clinical decision support tools are designed to ensure accurate medication dosing at the time of an initial prescription, few address the need for ongoing monitoring,” said first author Grace C. Herron, a fourth-year student at U-M Medical School.
“Any health system that aims to improve safe and effective DOAC prescribing must address the ongoing prescribing period which can last months to years.”
Direct oral anticoagulants became available in 2010 and quickly gained popularity because, unlike conventional blood thinners, they do not require routine monitoring to test their effectiveness.
However, these medications have their own complicated dosing schemes that can vary based on factors such as kidney function and select interactions between drugs.
“The hospital systems in the Michigan Anticoagulation Quality Improvement Initiative are leading national efforts to develop, implement and test anticoagulation stewardship teams that ensure patients are always receiving the safest and most appropriate blood thinner possible,” Barnes said.
“The nurses and pharmacists on these teams play a critical role in helping to monitor for any prescription issue that might develop, even months or years after a patient starts on a blood thinner medication.”
June Bellamy’s 83-year-old mother got COVID in March 2022 and was in intensive care for two weeks. She was diagnosed with heart disease. When she was discharged, she was put on oxygen and prescribed medication, including blood-thinning tablets containing rivaroxaban.
During a visit to the doctor earlier this month, Bellamy and her mother were shown a list of different medications containing rivaroxaban. But when they tried to obtain the generic version at the dispensary, which is about 40% cheaper, the supervisor said that because of an ongoing court case they were not allowed to supply it anymore.
“We’ve had to buy the expensive one,” says Johannesburg resident Bellamy, who has been unemployed since 2017. It costs her R1100 a month and she also has to buy other medications. She says her mother is on a basic medical aid plan and the medication is not covered.
“While I’m financially decimated, I’m trying to do what I can,” said Bellamy.
One year and counting
There are a number of court cases dealing with the issue. One of these is between Bayer and Clicks and was heard in the court of the commissioner of patents in Gauteng. The details are complicated and we explain them below. But what is clear is that in April 2022 Judge Colleen Collis reserved judgment in this urgent matter about the sale of blood-thinning tablets. More than a year later, she has failed to hand down her ruling.
In urgent matters judgment is expected almost immediately. It is astonishing for a judge to take a year over any judgment, let alone an urgent one. The judicial norms and standards state that judgments, in non-urgent matters, should be handed down within three months of being reserved.
GroundUp previously reported that the last available list of late judgments on the judiciary’s website is 31 December 2021. The judiciary has stonewalled our requests for an updated list.
We asked for comment from Chief Justice Raymond Zondo and Judge Collis but received no response.
What the case is about
The case deals with the extension of Bayer’s patent on rivaroxaban from December 2020 to January 2026.
In 2000, Bayer obtained a patent on rivaroxaban. Patents are granted for 20 years and so the patent was to expire in December 2020.
The patent-holder of a medicine, in this case Bayer, has exclusive control over it. No other pharmaceutical company may sell the medicine in South Africa during the patent period, at least not without Bayer’s permission. Effectively a patent holder has a monopoly. The point of patents is to create an incentive for pharmaceutical companies to develop new medicines.
In 2007 Bayer obtained a patent for rivaroxaban to be dosed once daily (the original patent was silent on dosing). This extended the patent to 19 January 2026. This kind of patent extension is widely criticised by health activists and is called evergreening.
After the initial patent expired in December 2020, two pharmaceutical companies, Austell and Dr Reddy’s, launched generic versions of rivaroxaban. To cut a long story short, there followed a series of court actions which resulted in Austell and Dr Reddy’s being interdicted from selling their versions of rivaroxaban in South Africa. But the interdicts did not yet stop the big three pharmacy groups, Dis-Chem, Alpha Pharm and Clicks, selling the stock they had of both generic products.
Dis-Chem and Alpha Pharm reached a settlement with Bayer in respect of Dr Reddy’s product, Rivaxored, but Clicks did not. Bayer applied to the court of the commissioner of patents to interdict Clicks from selling rivaroxaban and obtained an urgent interim interdict in March 2022. Shortly after that, in April 2022, the main (and still urgent) hearing for this application took place and Judge Collis reserved judgment. That is where matters stand, over a year later.
As of 13 May, OpenUp’s medicine price website gives the price of a pack of 42 Xarelto (Bayer’s rivaroxaban product) 15mg tablets as R1532. Austell’s equivalent product, Rezalto, is R931.26. Dr Reddy’s product, Rivaxored, is a little higher priced than Rezalto (at 15mg) but considerably lower than Bayer. There’s also iXarola, Bayer’s “authorised generic”, which they brought to market just before the expiry of the 2000 patent. It’s priced at R1285. (These prices exclude the dispensing fee.)
The timeline below contains more detail.
Timeline
2000: Bayer gets patent for rivaroxaban (expires December 2020).
2007: Bayer gets patent for dosing rivaroxaban once daily instead of twice daily (effectively means that the patent expires on 19 January 2026).
2020, December: Initial patent expires.
2021, January: Austell launches its generic version of rivaroxaban, called Rezalto.
2021, April 1: Dr Reddy’s launches its generic version of rivaroxaban, called Rivaxored.
2021, May: Bayer obtains urgent interdicts that stop Austell from selling Rezalto.
2021, December: Bayer obtains interim interdict against Dr Reddy’s, but the interdict does not extend to stopping pharmacies from selling the stock they already had of Dr Reddy’s generic pills.
2022, January: Bayer then launches another urgent application to interdict three pharmacy groups from selling Dr Reddy’s generic pills still in stock. Dis-Chem and Alpha Pharm reach a settlement with Bayer. But Clicks refuses to settle and opposes Bayer’s application.
2022, March 15: Bayer obtains an urgent interim interdict against Clicks at the court of the commissioner of patents in Gauteng, pending a main hearing which takes place at the same court in April.
2022, April: The urgent interdict application between Bayer and Clicks is heard by Judge Colleen Collis in the court of the commissioner of patents in Gauteng. Collis reserves judgment.
2023, May: Judgment has still not been handed down by Judge Collis.
The anticoagulant drug heparin is widely given to patients with blood clotting disorders or after surgery to prevent complications. But it remains difficult to dose correctly, potentially leading to overdosing or underdosing. A team of Penn State researchers combined heparin with a protein fragment, peptide, to slow down the release of the drug and convey the medication directly to the site of a clot. They published their findings in the journal Small.
“We wanted to develop a material that can gradually deliver heparin over time rather than the current iteration that gets cleared from the body in a couple of hours,” said corresponding author Scott Medina, Penn State associate professor of biomedical engineering. “We also wanted to deliver the drug through the skin instead of through an IV.”
When mixed, positively charged peptides and negatively charged heparin bind to create a nanogranular paste that can be injected under the skin, forming a cache of material that is then diffused in the circulatory system and travels to blood clots when they appear. The turbulent flow of fluid near a blood clot triggers the two materials to separate, allowing heparin to begin its anticoagulating action.
“The peptide is ideal for pairing with heparin because it essentially blocks heparin’s action until it is needed in the body,” said Atip Lawanprasert, doctoral student in biomedical engineering and first author on the paper. “The peptide also has some anticoagulating properties on its own: It binds to platelets in the blood, enabling action at the clotting site.”
Without an added bonding agent, heparin applies its anti-clotting properties indiscriminately, not just at blood clot sites, and clears quickly, its half-life only 60 to 90 minutes. Using preclinical animal trials, researchers determined that the addition of peptide allows for a dramatic increase of heparin’s half-life, to up to nearly 24 hours.
“The peptide increases heparin’s effects by more than ten times longer than what is currently being used,” Medina said. “The increased half-life allows for sustained treatments for patients, less medication waste and more accurate dosing. Eventually, this could allow the medication to be injected under the skin just once a day, rather than an all-day IV drip.”
Next, researchers plan to replicate the study in a clinical setting, as well as study the effect of the medication’s toxicity with multi-day administration.
A major UK-wide trial has found that the the oral anticoagulant apixaban does not help patients recovering from moderate and severe COVID compared to standard care – despite this approach being offered to patients.
To date, more than a thousand NHS patients hospitalised with COVID have taken part in HEAL-COVID, a platform trial that is aiming to find treatments to reduce the number who die or are readmitted following their time in hospital.
The trial’s preliminary results have shown that prescribing the oral anticoagulant Apixaban does not affect subsequent mortality or rehospitalisation of COVID over the following year (apixaban 29.1%, versus standard care 30.8%).
As well as being ineffective, anticoagulant therapy has known serious side effects, and these were experienced by participants in the trial with a small number of the 402 participants receiving apixaban discontinuing due to bleeding events.
There was also no benefit from Apixaban in terms of the number of days alive and out of hospital at day 60 after randomisation (apixaban 59 days, versus standard care 59 days).
Following these results, the trial will continue to test atorvastatin, which acts on other mechanisms of disease that are thought to be important in COVID.
Chief Investigator for the trial Professor Charlotte Summers is an intensive care specialist at Addenbrooke’s Hospital and the University of Cambridge. She said: “These first findings from HEAL-COVID show us that a blood thinning drug, commonly thought to be a useful intervention in the post-hospital phase is actually ineffective at stopping people dying or being readmitted to hospital. This finding is important because it will prevent unnecessary harm occurring to people for no benefit. It also means we must continue our search for therapies that improve longer term recovery for this devastating disease.”
HEAL-COVID enrols patients when they are discharged from hospital, following their first admission for COVID. They are randomised to a treatment and their progress tracked.
Nirmatrelvir-ritonavir (Paxlovid) is often given to heart disease patients with symptomatic COVID to prevent progression to severe disease – but it can interact with some previously prescribed medications. A review paper published in the Journal of the American College of Cardiology examines the potential drug-drug interactions (DDIs) between Paxlovid and commonly used cardiovascular medications, as well as potential options to mitigate severe adverse effects.
“Awareness of the presence of drug-drug interactions of Paxlovid with common cardiovascular drugs is key. System-level interventions by integrating drug-drug interactions into electronic medical records could help avoid related adverse events,” said Sarju Ganatra, MD, senior author of the review.
He continued: “The prescription of Paxlovid could be incorporated into an order set, which allows physicians, whether it be primary care physicians or cardiology providers, to consciously rule out any contraindications to the co-administration of Paxlovid. Consultation with other members of the health care team, particularly pharmacists, can prove to be extremely valuable. However, a health care provider’s fundamental understanding of the drug-drug interactions with cardiovascular medications is key.”
In December 2021, Paxlovid received emergency use authorisation from the US Food and Drug Administration as an oral antiviral agent for the treatment of symptomatic, non-hospitalised adults with mild to moderate COVID infection who are at high risk for progression to severe disease. Patients with heart disease and other risk factors, including diabetes, high blood pressure, chronic kidney disease and smoking make up a large portion of the high-risk population for whom Paxlovid is beneficial.
According to the authors, Paxlovid has been shown to be very effective in patients with existing heart disease, but it has significant DDIs with commonly used cardiovascular medications, highlighting the importance for all clinicians to be familiar with these DDIs. As there is limited clinical information regarding DDI-related adverse events, the authors used existing knowledge and data regarding how therapies like Paxlovid typically react with other medications to provide guidance regarding potential interactions and the associated likely consequences based on the degree of interaction.
The review provides an in-depth overview of a variety of cardiovascular medications used to treat many forms of heart disease. Five of the most important cardiovascular drug interactions with Paxlovid to be aware of include:
Anti-arrhythmic agents
Many anti-arrhythmic agents are metabolised in a way that increases plasma levels when co-administered with Paxlovid. While it may be possible to start Paxlovid after 2–2.5-day temporary discontinuation of the anti-arrhythmic agents, this may not be feasible from a practical standpoint. Clinicians are advised to consider alternative COVID therapies and avoid co-administration of these agents with Paxlovid. Sotalol, another anti-arrhythmic agent, is renally cleared and does not interact with Paxlovid.
Antiplatelet agents and anticoagulants
Antiplatelet agents are used for the treatment of coronary artery disease, particularly if a patient has received a stent. Aspirin and prasugrel are safe to co-administer with Paxlovid. There is an increased risk of blood clots when Paxlovid is given alongside clopidogrel and an increased risk of bleeding when given with ticagrelor. When possible, these agents should be switched to prasugrel. If patients have contraindication to taking prasugrel, then co-administration of Paxlovid should be avoided and alternative COVID therapies should be considered.
Anticoagulants such as warfarin may be co-administered with Paxlovid but require close monitoring of clotting factors in bloodwork. The plasma levels of all direct oral anticoagulants increase when co-administered with Paxlovid, therefore dose adjustment or temporary discontinuation and use of alternative anticoagulants may be required.
Certain statins
Co-administration of simvastatin or lovastatin with Paxlovid can lead to increased plasma levels and subsequent myopathy and rhabdomyolysis, a condition in which the breakdown of muscle tissue releases a damaging protein into the bloodstream. These agents should be stopped prior to initiation of Paxlovid. A dose reduction of atorvastatin and rosuvastatin is reasonable when co-administered with Paxlovid. The other statins are considered safe when given along with Paxlovid.
Ranolazine
Plasma concentration of ranolazine, used to treat angina and other heart-related chest pain, is exponentially increased in the presence of CPY450 inhibitors like Paxlovid, thereby increasing the risk of clinically significant QT prolongation and torsade de pointes (a type of arrhythmia). Co-administration of Paxlovid is therefore contraindicated. Temporary discontinuation of ranolazine is advised if prescribing Paxlovid.
Immunosuppressive agents
The plasma levels of immunosuppressive agents prescribed for patients who have undergone heart transplantation exponentially rise to toxic levels when co-administered with Paxlovid. Temporary reduction of dosing of immunosuppressive agents would require frequent monitoring and be logistically difficult. Therefore, alternative COVID therapies should be considered in these patients.
The authors conclude awareness and availability of other COVID therapies enable clinicians to offer alternative treatment options to patients who are unable to take Paxlovid due to DDIs.
