Year: 2021

Categories : Medical Research & TechnologyTags :

Nicotine Linked to Sleep Apnoea Risk

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In a first-of-its-kind, scientists from the Heart Research Institute (HRI) have made the link between amounts of nicotine in the blood and their sleep apnoea risk.

Sleep apnoea occurs when a person’s throat and upper airway become partly or totally blocked during sleep, causing short periods where breathing ceases.

In a new paper published in ESC Heart Failure, Heart Research Institute (HRI) scientists found increases in nicotine levels were associated with a 2.3 minute increase in the time spent with oxygen saturations below 90%.

One of the markers of severity of sleep apnoea is time spent with an oxygen saturation less than 90%.

Lead researcher Dr John O’Sullivan, said this meant that for every cigarette a person smoked, the more they increased the risk of “dangerously low” oxygen levels.

“People who spend more time with an oxygen saturation less than 90 percent end up with more cardiovascular death than people who don’t,” Dr O’Sullivan said.

“We know smoking is bad for the heart – it’s one of the major risks for heart attacks – and although smoking is known to reduce oxygen concentration in the blood, the interaction of smoking with sleep apnoea has not been quantified. Using blood concentrations of the major nicotine metabolite, we were able for the first time to quantify the effect of smoking on oxygen concentrations at night in people with sleep apnoea.

“A standardised increase in levels of this metabolite was associated with 2.3 more minutes with an oxygen concentration less than 90 percent in people with sleep apnea. Time with an oxygen concentration less than 90% is a proven indicator of bad cardiovascular outcome.”

Sleep apnoea and congestive heart failure comorbidities are common, but their interaction is unclear. To find out more, Dr O’Sullivan’s team used hundreds metabolites to understand this interaction.

“Believe it or not, stiff heart failure – when the heart muscle can still pump blood but is stiff and cannot relax properly – is the most common form of heart failure today and we have almost no treatment options,” Dr O’Sullivan said.

“We measured molecules in the blood called metabolites and looked at the changes in these metabolites and related these to the severity of sleep apnoea.”

Metabolomics is a relatively new field of study that investigates metabolites, which are the components of your metabolism and play key roles in disease. They can provide insight into how one disease is linked to another, like in this case the consequences of sleep apnea and heart failure. Several metabolites are also key fuels for the working heart, and others form the units of energy by which the heart works.

The team studied metabolites and lipids in 3443 people from two US studies, including the landmark Framingham study.

Dr O’Sullivan said Framingham was known as the “town that changed America” because of the multi-generational study started in 1948 that subsequently identified the cardiovascular risk factors we still use today. Much research using this study is openly available internationally, enabling researchers around the world.

“Accurate measurement of disease combined with blood metabolite levels is far more accurate than self-reported questionnaires – that’s one of the strengths of this study,” he said.

While sleep apnoea is very common (up to one in four adults), its consequences and interactions with other diseases remain poorly understood. Almost no studies  have sleep study data, heart failure data, and metabolomic data in the same individuals, which is a major new feature of this study.

Source: Heart Research Institute

Categories : Cancer UncategorizedTags :

An Inspiration Led to Understanding Metformin’s Anti-tumour Effect

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Scientists report that metformin, used to treat type 2 diabetes mellitus, induces activation and proliferation of tumor-targeting CD8+ T-lymphocytes (CD8TIL), via mechanisms that involve the generation of reactive oxygen species in mitochondria of CD8TIL and an increase in glycolysis. Credit: Heiichiro Udono from Okayama University

Researchers in Japan have elucidated how the antidiabetic drug metformin exerts an anti-tumour effect as well.

Certain drugs like metformin have recently been found to have anti-cancer properties. Metformin appears to bolster anti-tumour immunity but the underlying immunological mechanisms were a mystery. With all the permutations and combinations of cancer, a blanket, yet targeted therapy would be ideal. 

Japanese scientists led by Professor Heiichiro Udono from Okayama University thus decided to address this oncological research question. In their recent study, they looked at how a specific subset of immune cells, called CD8+ infiltrating T-lymphocytes (CD8TIL), which specifically attack tumor cells, behaved in response to metformin. Their findings have been published as a research article in Journal for ImmunoTherapy of Cancer.

Interestingly, Prof. Udono almost gave up on his anti-cancer pursuits, when he lost his own father to cancer. However, a bolt of inspiration came at a conference: “Nearly 10 years ago, a switch turned on in my head when I attended a Keystone Symposia discussing cancer, and hypoxia, held in Banff, Alberta. I realised that we had missed addressing Warburg effect, an effect which bolsters the growth of cancer, in our previous research. So, reverting Warburg effect to normal metabolic profile in cancers became a topic that got me thinking. Surprisingly, I got a hint from the same conference that metformin may aid cancer immunity. So, we got to work!”

Prof Udono and his team got to work, meticulously conducting a series of experiments on cancer cell lines, and ‘knockout gene’ mice, searching for possible biomolecules that result in metformin-dependent anti-tumour immunity. They probed the intracellular mechanisms in CD8TIL, when exposed to metformin, and assessed different biomarkers for growth. Given that CD8TIL produces proteins called interferons to attack cancer cells, they also assessed corresponding levels.

Accordingly, the scientists found that metformin causes the generation of reactive oxygen species in the mitochondria of CD8TIL (mtROS) and increases glycolysis. They also found that mtROS activated growth pathways in CD8TIL, allowing these cells to proliferate. Notably, this is achieved through a transcription factor involved in anti-oxidative stress response, called Nrf. Though metformin did not directly cause apoptosis, ‘cell suicide’ in tumours, it did cause CD8TIL to secrete interferon-ɣ to alter the tumour microenvironment in favour death of tumour cells.

Summing up the findings, Prof. Udono said: “More than anything else, our study provides the knowledge that we can ourselves protect our body from cancer. We hope that this understanding will result in not only the reduction of cancer incidence and improve treatment, but also will help prolong our life.”

The researchers also added that these findings strongly suggest the possibility of using metformin as a drug to strengthen anti-tumour immunity in patients with cancer. The findings appear in the Journal for ImmunoTherapy of Cancer.

Source: EurekAlert!

Categories : HIVTags :

HIV-infected Cells Use Sugars to Avoid Immune Destruction

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HIV invading a human cell
HIV invading a human cell: Credit NIH

A new study shows how key features on the surface of HIV-infected cells such as certain sugar molecules help the disease evade detection by the immune system, and how they can be disabled. The findings, published in PLOS Pathogens, represent a first step to eradicating this persistent virus in patients.

“We identified a glyco-immune checkpoint interaction as a novel mechanism that allows HIV-infected cells to evade immune surveillance,” said Mohamed Abdel-Mohsen, PhD, assistant professor in the Vaccine & Immunotherapy Center at The Wistar Institute and coauthor on the paper. “And we developed a novel approach that selectively targets these interactions on the surface of these infected cells.”

Existing treatments can reduce HIV to undetectable levels, but eradication remains elusive, with the disease typically returning quickly when treatment stops. And even when controlled, HIV increases risk for other health problems, including neurological disorders, cardiovascular disease, and cancer.

For the new study, researchers looked at a type of sugar molecule called sialic acid on the surface of HIV-infected cells. These sugars bind with receptors called siglecs on the surface of disease-fighting ‘natural killer’ immune cells. When activated, these receptors act as inhibitors, restraining the killer cells and causing them to stop killing. “We thought, ‘is it possible that these HIV-infected cells are using this interaction – covering themselves with these sugars to evade the natural killer immune surveillance?’” said Prof Abdel-Mohsen.

The researchers found that these infected cells can actually exploit this inhibitory connection to evade immune surveillance. They then investigated whether they could manipulate this connection to make the killer cells more effective at killing HIV-infected cells. Disabling the inhibitors from the killer cells was found to cause the immune cells to attack indiscriminately. The researchers turned to the HIV cells, using the enzyme sialidase to remove the sialic acid sugars that were activating the immune inhibitors but this affected all cells, again causing the killer cells to attack indiscriminately. Finally, they developed a sialidase conjugate linked to HIV antibodies, which only targeted sialic acid on HIV cells. With the sialic acid removed from these cells, the killer immune cells attacked and killed the HIV-infected cells, leaving healthy cells alone.

“The killer cells become a super killer for the HIV-infected cells and they now attack them in a selective manner,” said Prof Abdel-Mohsen. “The discovery could be a missing link in the “shock and kill” approach to HIV treatment that has been a focus of research for the past several years,” he added. This two-step process involves first “shocking” the HIV out of latency so it can be detected, and then stimulating the immune system to “kill” the virus once and for all. However, while effective methods have been discovered to reverse latency, scientists haven’t yet found a way to make HIV-infected cells more killable once reactivated. “We may have the shock, but we don’t yet have the kill,” Prof Abdel-Mohsen said. “Our method actually increases the susceptibility of HIV-infected cells to killing, which is one of the top unmet needs in the HIV field.”

First author Samson Adeniji, Ph.D., a postdoctoral fellow at Wistar, noted that the team’s approach could be tested in combination with broadly neutralizing antibody therapies currently being studied in clinical trials. “By combining approaches, we could turn these immune cells from a cop into a kind of Robocop,” he said.

The researchers also noted that, besides  HIV, the approach could be applied in infectious diseases that may evade the immune system, including hepatitis and COVID. In vivo tests with animals are the next step. They’re also investigating other sugar molecules on HIV that may play a similar role as sialic acid. “HIV-infected cells are likely evading immune surveillance through many potential glyco-immune checkpoints,” Abdel-Mohsen said. “We are investigating other mechanisms and how to break them.”

Source: Wistar Institute

Categories : Diet and Nutrition Obstetrics & GynaecologyTags :

Moderate Caffeine Intake May Reduce Gestational Diabetes Risk

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Pregnant coffee lovers can breathe a sigh of relief, as consuming a low amount of caffeine during pregnancy could help to reduce gestational diabetes risk, according to a new study published in JAMA Network Open.

“While we were not able to study the association of consumption above the recommended limit, we now know that low-to-moderate caffeine is not associated with an increased risk of gestational diabetes, preeclampsia, or hypertension for expecting mothers,” said the study’s lead author Stefanie Hinkle, PhD, an assistant professor of Epidemiology at the University of Pennsylvania.

The current recommendation from the American College of Obstetricians and Gynecologists (ACOG) is that pregnant women limit their caffeine consumption to less than 200 mg (about two cups) per day. The recommendations are based on studies that suggest potential associations with pregnancy loss and foetal growth at higher caffeine levels. However, there remains limited data on the link between caffeine and maternal health outcomes.

To better understand this association, researchers studied prospective data from 2529 pregnant participants from 2009 to 2013.

At enrollment and at each visit thereafter, women reported their weekly intake of caffeinated coffee, caffeinated tea, fizzy drinks, and energy drinks. Concentrations of caffeine were also measured in the participants’ plasma at 10 to 13 weeks into their pregnancies. The researchers then matched their caffeine consumption with primary outcomes: clinical diagnoses of gestational diabetes, gestational hypertension, and preeclampsia.

The research team found that caffeine at 10 to 13 weeks gestation was not related to gestational diabetes risk. During the second trimester, drinking up to 100 mg of caffeine per day was associated with 47% less diabetes risk. No statistically significant differences in blood pressure, preeclampsia, or hypertension between those who did and did not consume caffeine during pregnancy.

The findings are in line with research that found an association between and improved energy balance and decreased fat mass, the researchers noted. However, other constituents of coffee and tea such as phytochemicals could be the cause.

The group’s previous work has however shown that caffeine consumption during pregnancy, even in amounts less than the recommended 200 mg per day, was associated with smaller neonatal anthropometric measurements, according to Prof Hinkle.

“It would not be advised for women who are non-drinkers to initiate caffeinated beverage consumption for the purpose of lowering gestational diabetes risk,” she said. One meta-analysis found that any amount of caffeine was a risk to the foetus. “But our findings may provide some reassurance to women who already are consuming low to moderate levels of caffeine that such consumption likely will not increase their maternal health risks.”

Source: Penn Medicine

Categories : PoliticsTags :

NHI Implementation on the Financial Rocks – For Now

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South Africa’s National Health Insurance (NHI) implementation continues to flounder, as the National Treasury notes its expenditure will not be a significant cost in the medium term. This scheme, which seeks to address the country’s huge gulf in healthcare inequality, has still made barely any progress since its inception over a decade ago.

In its Medium Term Budget Policy Statement published on Thursday (MTBPS), the Treasury said that the national health insurance policy was estimated to cost R40 billion per year in additional funding in the first five years, and perhaps considerably more over time. Therefore, it dismissed the possibility of any substantial work on it, saying that presently, “there is insufficient capacity in the health sector to work substantively on national health insurance. The national health insurance indirect grant has been underspent, the National Health Insurance Fund has not yet been established, and the National Health Insurance Bill still needs to be passed by Parliament.

“It is therefore unlikely that national health insurance will be a significant cost pressure in the medium term,” it said.

While the Department of Health has time and again reiterated its commitment to the NHI system, several studies highlight the system’s deep unpopularity among healthcare professionals. 

“To fund this, we need taxpayers,” said senior researcher Morné Malan at Solidarity Research Institute, when former Health Minister Dr Zweli Mkhize tabled the NHI Bill in Parliament in August 2019.

“To be a taxpayer you must be employed… only 12% of South Africans pay tax.”

In August 2021, trade union Solidarity published a report drawing on three surveys from 2018 to 2021, with 20.8% of respondents already preparing to leave.

Across the studies, the overarching response from healthcare professionals is one of uncertainty and mistrust around the NHI, with general sentiment towards the system being overwhelmingly negative.

“Almost all the respondents have serious concerns regarding the state’s ability to manage and administer the NHI,” Solidarity said. “The total administration and management of funds and decision-making will be in the hands of the state.

“Most are seriously concerned about the fact that the state can determine and enforce tariffs, place of work, type of diagnostic tests and type of medication and treatment.”

The opinions of those surveyed are likely shaped by the observed mismanagement and maladministration at state institutions such as Eskom, Solidarity noted. The NHI will be considerably larger and more complicated, and will have to manage and execute many contracts, it said.

Source: Businesstech

Categories : COVID VaccinesTags :

WHO Predicts Shortfall in Syringe Production

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The World Health Organization has said that with the goal of two COVID vaccine doses for seven billion people between now and 2023, a shortage of at least one billion syringes “could occur”, if manufacturing does not increase. This could endanger other immunisation programmes.

Lisa Hedman, WHO Senior Advisor, from the Access to Medicines and Health Products division, warned that there could be a generation of children who miss scheduled immunisation jabs unless manufacturers come up with a way to make more single-use disposable syringes.

“When you think about the magnitude of the number of injections being given to respond to the pandemic, this is not a place where we can afford shortcuts, shortages or anything short of full safety for patients and healthcare staff,” said the WHO expert.

She told media that more than 6.8 billion doses of COVID vaccines are being administered globally per year – nearly twice the yearly number for routine inoculations.

“A shortage of syringes is unfortunately a real possibility and here’s some more numbers. That [given] the global manufacturing capacity of around six billion a year for immunisation syringes it’s pretty clear that a deficit in 2022 of over a billion could happen if we continue with business as usual.”

Reuse of syringes was inadvisable, also noting that syringes were particularly prone to transport delays because they took up 10 times the space of a vaccine.

Meanwhile, the heads of the International Monetary Fund (IMF), World Bank Group, WHO and the World Trade Organization (WTO) held a follow up session of High-Level Consultations with the CEOs of leading COVID vaccine manufacturing companies on Tuesday.

All participants at the meeting agreed on the urgency of increased vaccine dose delivery to low-income countries, where less than 2.5% of the population has been fully vaccinated.

The meeting’s aim was to identify how to ensure more equitable distribution of vaccines and all participants pledged to continue working together to clarify donations, vaccine swaps and delivery schedules, so that distribution of the life-saving vaccines can be more effectively targeted towards needy countries.

The meeting of the Multilateral Leaders Task Force on COVID-19 built on technical work undertaken by multidisciplinary teams during the months of September and October.

During the consultations, the leaders of the four organisations and the CEOs also examined how best to tackle trade-related bottlenecks; how to improve the donation process; what additional steps are needed to reach the vaccination target of 40% of people in all countries by the end of the year; and how to improve transparency and data sharing with the IMF-WHO Vaccine Supply Forecast Dashboard and the Multilateral Leaders Task Force.

The effort will require close collaboration between manufacturers, governments and the international COVAX initiative, on enhanced delivery schedules, especially for doses that are being donated.

Source: UN News

Categories : Medical Research & TechnologyTags :

Why Some Drugs Have Side Effects

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Researchers have discovered how unwanted side effects can result from how some drugs affect various membrane-spanning proteins in addition to their intended target. The findings, published in PNAS, illuminate one of the main problems of drug discovery and point to new strategies to overcome it.

Any class of drug can have side effects, but those that interact directly with cellular membranes have been especially problematic. “Those drugs tend to affect many membrane proteins, and we suspected that there’s some kind of non-specific mechanism at work,” said first author Dr Radda Rusinova, assistant professor of research in physiology and biophysics at Weill Cornell Medicine. “We wanted to see whether it could be linked to the cell membrane.”

Dr Rusinova and her colleagues used sensitive assays that allowed them to compare how different drugs affected the activities of two channel proteins that span membranes: the gramicidin ion channel and a potassium channel called KcsA. Gramicidin was used to measure the magnitude of drugs’ effect on the membrane while KcsA reflected effects these drugs could have on typical membrane proteins.  They found that membrane-associated drugs can affect KcsA in at least three ways: by interacting directly with the proteins, by interfering with the proteins’ structural connections to the membrane, or by causing broad changes in membrane characteristics such as thickness or elasticity.

Changes in membrane characteristics have well-known effects on the gramicidin ion channel, an antibiotic isolated from bacteria that has long been used as a standard tool for studying such changes. “Gramicidin is a probe essentially for changes in bilayer and membrane properties, and will report on the magnitude of the changes,” said Dr. Rusinova.

“But we needed to go further to see how a more typical cell membrane protein would react,” Dr. Rusinova said. KcsA belongs to a class of proteins – potassium channels – that drive many aspects of cell physiology in everything from bacteria to humans, making it a good comparative probe.

The comparative assay results revealed a more nuanced process than the  straightforward model currently used to explain how membrane-binding drugs can affect membrane-spanning proteins.

“The more data that Dr Rusinova got, the more it became apparent that this simple model did not actually cover the full spectrum of effects that we saw,” said senior author Dr Olaf Andersen, professor of physiology and biophysics.

“The investigators who are looking into molecules that can move into the cell membrane need to worry about at least three mechanisms for off-target effects,” Dr Rusinova said.

However, not all is bad news: in some cases, off-target effects at the cellular level cause no trouble to the organism, and in a few instances they can even be beneficial. Dr Rusinova points to two of the drugs her team tested as an example: amiodarone, a heart medication whose membrane-mediated effects actually boost its efficacy, and troglitazone, an anti-diabetic drug whose side effects included liver toxicity, ultimately forcing regulators to pull it from the market.

The investigators hope to develop more predictive models for such off-target effects. “We would like to determine the structural characteristics of a membrane protein that would make it more or less sensitive to bilayer effects,” Dr Rusinova said.

Source: Weill Cornell Medicine

Categories : Metabolic DisordersTags :

A Needle-free Way of Blood Glucose Monitoring

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In order to find an alternative to lancets for blood glucose monitoring, researchers applied needle-free jet injection, an emerging but well-developed technique in which a drug is delivered directly with a high-speed narrow jet of fluid.

The study, led by ABI researchers Jiali Xu and James McKeage, demonstrated for the first time that a jet injector could also be used to collect blood samples from humans – that is, release enough blood for glucose sampling, sans needles. The findings appear in the Journal of Diabetes Science and Technology.

Fingertips are the preferred site for blood sampling because they have a high density of blood vessels, they are also sensitive, and pain, skin damage, bruising and risk of infection from regular ‘pricking’ has spurred increasing efforts to develop needle-free methods of blood testing for people with diabetes.

Jet injection, which does not rely on a needle, is an appealing alternative. Jiali Xu of the Auckland Bionengineering Institute (ABI) and her team demonstrated that the technology, using electric motors rather than the standard mechanical spring, could also be used to pierce the skin with a small volume of harmless saline solution, releasing enough blood for glucose concentration measurement.

The study involved 20 healthy participants, each of which received a lancet prick and jet injection on four fingertips through three differently shaped and sized nozzles. “Which were designed to mimic the wound left from a lancet prick, in the anticipation that it might release blood in a way similar to a lancet prick,” said Ms Xu.

Some nozzle shapes performing better than others – a ‘slot’ shaped nozzle released more blood than a circle-shaped nozzle, for instance.

Most of the different jet injection nozzles were generally perceived by the participants, who were unable to see the injections, as no more painful than a standard lancet, and in some cases, less so. A questionnaire was given 24 hours later to assess pain, swelling and bleeding.

People with diabetes may find jet injection more acceptable than using a needle, but the researchers caution against jumping to conclusions. “When you know there’s not a device that is pricking your skin, you could speculate that people will find jet injection more acceptable,” says Professor Andrew Taberner, head of the Bioinstrumentation Lab at the ABI, and Ms Xu’s supervisor. “But we don’t have evidence to back that up. That wasn’t part of this study. We were first trying to find out if it worked, and it did.”

He was pleased, but not surprised. “Diesel mechanics have known for years that you should never put your finger in front of a fuel injector, because it will inject fuel into your finger. They found this out the hard way. But we’re taking advantage of what diesel mechanics discovered accidentally years ago, with a very small amount of harmless liquid, to deliberately release blood.”

The team is now trying to see if they can also extract blood with this technology, allowing for the design of an even smaller nozzle.

Moreover, “our technology has the capability to both deliver and withdraw fluid. No other jet projection technology has that capacity,” said Dr Taberner.

Development and commercialisation of the technology will take time but he believes Ms Xu’s research will contribute to the ultimate aim, of the development of a single lancet-free reversible technology that will allow for both blood sampling and insulin delivery based on the glucose measurement in one device.

“I hope that this research will contribute to that, and the improvement in human healthcare, especially in the management of diabetes,” said Ms Xu.

Source: University of Auckland

Categories : Genetics NeurologyTags :

Scientists Identify A New Recessive Neurodevelopmental Disorder

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Image source: Pixabay

In the Journal of Clinical Investigation, researchers have reported a rare neurodevelopmental condition characterised by intellectual disability, ataxia with cerebellar hypoplasia and delayed puberty with hypogonadotropic hypogonadism (HH).

Patients with this unusual combination of conditions were referred to Mehul Dattani (UCL), and affected individuals were found to carry the same homozygous mutation in the PRDM13 gene, which encodes a chromatin modifying factor that contributes to regulating cell fate. Intriguingly, an unaffected heterozygous carrier of this mutation was identified by screening 42 unaffected individuals in the Maltese population, suggesting that this mutation is present at low levels in the population.

The researchers set out to model this condition and identify the underlying causes using a PRDM13-deficient mouse model. The researchers found evidence that both the cerebellar hypoplasia and reproductive phenotypes resulted from defects in the specification of specific populations of GABAergic neuronal progenitors in the developing cerebellum and hypothalamus, respectively.

The results indicate that this condition results from abnormal cell fate specification during development. Consequently, the hypoplastic cerebellum is deficient in molecular layer interneurons, which play critical roles in regulating cerebellar circuits. In the hypothalamus, fewer Kisspeptin neurons, which are important regulators of gonadotropin releasing hormone and puberty, were present in PRDM13 mutant mice.

Together, these findings identify PRDM13 as a critical regulator of neuronal cell fate in the cerebellum and hypothalamus, providing a mechanistic explanation for the co-occurrence of hypogonadism and cerebellar hypoplasia in this syndrome.

Source: King’s College London

Categories : Cardiovascular DiseaseTags :

Guidelines for Percutaneous Coronary Intervention May Need Changing

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Percutaneous coronary intervention (PCI) is often performed after a heart attack, or to alleviate symptoms of chest pressure, but a new study published in Nature questions the efficacy of the current guidelines. 

Current American Heart Association guidelines recommend that patients who undergo PCI, a minimally invasive procedure to open clogged arteries, be prescribed dual antiplatelet therapy (DAPT) to prevent blood clots, and that they continue using the combination of aspirin and a second antiplatelet medication for at least one year after the procedure with continuation of DAPT beyond one year for patients with acceptable bleeding risk.

The current guidelines are based on previous research, including the DAPT Study, a large clinical trial 10 years ago of patients undergoing PCI with a stent, that found using DAPT beyond one year after PCI decreased ischaemic events but posed a higher risk of bleeding. Since then, questions have arisen as to whether the evidence is representative of real-world populations and changing practice patterns.

To better understand whether the results of prior trials of DAPT duration are applicable today, researchers at Beth Israel Deaconess Medical Center (BIDMC) developed new analytic methods to update a previously conducted trial to better reflect contemporary practice. The findings, published in Circulation, suggest that because of improvements in stent technology and changes in the types of patients receiving stents, the risks of DAPT may now outweigh the benefits for the average patient.

“Clinical research can become outdated as practices and technologies evolve,” said corresponding author Robert W. Yeh, MD, MSc, an interventional cardiologist at BIDMC. “By extrapolating what an older trial might have shown had it been conducted today, we found that many patients who’ve received stents and are currently on combination antiplatelet therapy may actually benefit from stopping one of those antiplatelet drugs – adding to growing evidence that aspirin and drugs like it may be less useful than previously thought.”

Yeh and colleagues extrapolated the results of 5743 DAPT Study participants to national data from 568 540 patients undergoing PCI with a stent. Using new analytic methods, the team estimated a contemporary “real-world” treatment effect of 30 months versus 12 months of DAPT after coronary stent procedures. Compared to the previous trial population, contemporary registry patients had more comorbidities and were more likely to present with heart attack and receive second generation drug-eluting stents. After adjustment to represent the registry population, the researchers no longer saw a significant effect of prolonged DAPT on reducing stent thrombosis or heart attack, but increased risk of bleeding persisted.

Additionally, the team used their previously developed risk tool called the DAPT Score to stratify subgroups of patients who may or may not benefit from prolonged DAPT. They found that the projected ischemic benefits of prolonged DAPT in the subgroup of patients with DAPT score less than two disappeared, while the bleeding risk persisted. In contrast, in the subgroup of patients with DAPT score of two or greater, ischemic benefits of prolonged DAPT persisted, though were slightly attenuated, with negligible increase in bleeding.

“While patients at highest risk of ischaemic event, [a] small group of patients should likely remain on these medications, longer duration DAPT may have more limited benefits and greater harms for most,” said lead author Neel M. Butala, MD, MBA, a research fellow in the Smith Center. “These results illustrate the importance of a nuanced interpretation of clinical trials to guide clinical decision-making. The methods may be applicable across various cardiovascular conditions to help ensure that evidence is up-to-date and appropriate for real world populations.”

Source: Beth Israel Deaconess Medical Center