VACC benefits - VACC Vascular Access Updated: 2023

(CNN) - Results from a landmark clinical trial this summer suggested, for the first time, that a medication given for weight loss alone could reduce the risk of heart attack, stroke or heart-related death in people with cardiovascular disease, bolstering physicians' excitement about an already-exploding class of new medicines.

Novo Nordisk's Wegovy, part of the booming group of drugs called GLP-1 receptor agonists, was shown to reduce those people's risk of another cardiovascular event by 20%, results that were confirmed in a presentation of the full dataset Saturday at the American Heart Association conference in Philadelphia.

"Imagine a future where we're treating obesity and, in effect, treating these other obesity-related diseases" like hypertension, high cholesterol and type 2 diabetes, Dr. Ania Jastreboff, director of the Yale Obesity Research Center, who helped conduct the trial, said at a briefing Friday. "Treating obesity clearly improves health outcomes."

A key question about the initial results, though, remained not fully answered: Is the heart benefit from Wegovy attributable to how much weight people lose while using the medicine? Or is it because Wegovy has other effects as well?

"It remains unclear to what degree the trial findings were dependent on weight loss, concomitant reductions in risk factors, or other salutary mechanisms of GLP-1 receptor agonism," Dr. Amit Khera, of the University of Texas Southwestern Medical Center Dallas, and the National Institutes of Health's Dr. Tiffany M. Powell-Wiley wrote in an editorial that was published Saturday in the New England Journal of Medicine along with the full results of the study, called Select.

Nonetheless, they added, "We are in a new era of treating obesity and cardiometabolic risk with a growing armamentarium of options."

The tool chest grew this week with US Food and Drug Administration approval of Zepbound for obesity, a drug from Eli Lilly that will compete directly with Wegovy. Both medicines were preceded by drugs for type 2 diabetes that use the same active compounds: Wegovy's sister drug is Ozempic, and both use semaglutide, while Zepbound's is Mounjaro, and both use tirzepatide. They're all taken once a week as a self-administered shot.

GLP-1 receptor agonists mimic hormones that stimulate the production of insulin, promote feelings of fullness and reduce appetite. Semaglutide targets GLP-1, while tirzepatide targets both GLP-1 and a hormone called GIP.

The trial showed that after two years, people using Wegovy were less likely to develop diabetes or blood sugar levels considered "prediabetes"; lost 9.4% of their body weight, compared with 0.9% on placebo; reduced their waist circumference by an additional 6.6 centimeters over placebo; and had greater reductions in systolic blood pressure, a marker of inflammation called C-reactive protein and triglycerides.

To cardiologist Dr. Steven Nissen of the Cleveland Clinic, who wasn't involved in the trial but is leading a similar one of tirzepatide, those effects are all evidence of the benefits of weight loss.

"When you lose weight, a lot of things change," Nissen said in an interview Saturday from the conference just after the Wegovy study presentation, which was given to a packed house with several rows of audience members standing at the back.

"We now have, for the first time in history, treatments that can actually really [help patients] lose enough weight to make a difference," Nissen said.

Tirzepatide has shown greater levels of weight loss than semaglutide in clinical trials, leading many, including Nissen, to hope it will show even stronger cardiovascular benefits.

The Wegovy study, sponsored by Novo Nordisk, enrolled 17,604 people whose body mass index was 27 or higher, putting them in the overweight category, and who had cardiovascular disease, meaning a previous heart attack or stroke or symptoms of peripheral artery disease - clogged arteries in the arms or legs.

Importantly, participants didn't have a history of diabetes; a previous trial had shown that treating people with diabetes with a GLP-1 drug, Ozempic, reduced their cardiovascular risk.

The Wegovy trial showed that 569 of 8,803 people taking the drug had a heart attack or stroke or died from heart-related causes, or 6.5%. That's compared with 701 of 8,801 people on a placebo, or 8%. The difference in those rates is what amounts to the 20% benefit reported in August.

The benefit was seen on top of medicines like statins to lower cholesterol, which 90% of the trial participants were taking, and other drugs considered the standard of care for heart patients.

"The differences in rates between the two treatment groups began to emerge very early after initiation of treatment, within the first months," the Cleveland Clinic's Dr. A. Michael Lincoff, who led the trial, said Friday.

The 20% reduction was on a combination of three measures; when looked at separately, not all reached statistical significance. The first individual measure the researchers looked at was death from cardiovascular causes, and while it appeared Wegovy lowered the risk by 15%, the results weren't statistically significant, meaning they don't hold as much weight.

The biggest benefit appeared to be in preventing heart attacks, where the risk reduction was 28%. Strokes were reduced by 7%. It's unclear what the statistical significance of those measures was, because researchers didn't calculate those values after the finding on deaths didn't meet the threshold. The overall finding of 20% risk reduction, though, was statistically very strong.

The study didn't uncover any new safety concerns, but it found that more people stopped taking semaglutide than placebo because of adverse events. The most common were gastrointestinal disorders like nausea, vomiting and diarrhea, and there was a small increase in gallbladder-related disorders on Wegovy compared with placebo.

The amount of weight loss seen in the trial, 9.4%, was less than in other studies of Wegovy, which showed average weight loss closer to 15%. Lincoff noted that this trial wasn't focused on weight management, where trials typically involve changes in diet and exercise and "close monitoring," but instead "models the way cardiovascular disease is treated in the real world."

He also noted that not all of the participants got the highest dose of Wegovy in this study; the dose of medicine was adjusted based on whether they had side effects.

On the question of whether the benefit in the trial came primarily from weight loss or from other drug effects, Lincoff pointed out that the heart benefits became apparent in the study earlier than the major differences between Wegovy and placebo on weight loss, and he noted that "lighter-weight patients to start with experienced the same magnitude of benefit."

"I think most of us believe that some of this is weight loss, but I think that that oversimplifies a very complex molecule, a complex receptor on multiple tissues, and I don't think it's as a simple as that," he said. "That's part of the reason why I don't think weight loss itself is the surrogate; we have to look at the mechanism of the weight loss."

"And," Jastreboff added, "it may be a combination of both."

The study left a few additional questions unanswered: It looked at heart risk only in people with existing cardiovascular disease, and researchers said it would be important to know whether the drug could benefit people who hadn't had a cardiac event. The trial also had racial and gender imbalances: Only 3.8% of participants overall were Black, and 28% were women.

The findings are expected to increase demand for the drug, which already is in short supply, and potentially Improve insurance coverage, which is spotty. Wegovy costs $1,349 a month before insurance.

And while "millions of additional patients" could benefit from the drug based on these results, Khera and Powell-Wiley wrote in their editorial, "semaglutide comes with a significant cost both to patients and to society at the current pricing for GLP-1 receptor agonists, which makes this treatment inaccessible for many."

Women with high blood pressure during pregnancy had long-term blood pressure and cardiac benefits if their blood pressure was carefully controlled for the first few weeks after having a baby, according to late-breaking science presented today at the American Heart Association's Scientific Sessions 2023. The meeting, Nov. 11-13, in Philadelphia, is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science. The full manuscript is also simultaneously published today in The Journal of the American Medical Association.

The heart undergoes significant changes during any pregnancy to cope with the increased circulatory demands of the growing baby, and these changes are much more profound during a hypertensive pregnancy, because of the increased stress of the pregnancy. Women who have had uncontrolled high blood pressure during pregnancy are at significantly greater risk of complications with their heart longer term. One-third develop hypertension again within 10 years of pregnancy and their risk of early heart attack and stroke are doubled."

Paul Leeson, M.B., B.Chir., Ph.D., lead study author, professor of cardiovascular medicine, University of Oxford, United Kingdom

In this prospective, randomized trial conducted in the U.K., researchers investigated the effects of improving blood pressure control immediately after pregnancy on long-term blood pressure levels.

This study included 220 new mothers who had high blood pressure during pregnancy and still needed medication for high blood pressure after giving birth.

Half of the participants were randomly assigned to the group that received a wireless blood pressure monitor and asked to send daily blood pressure readings via a phone app to the study doctors. The phone and app were connected to the blood pressure monitor via Bluetooth, and blood pressure measures were automatically uploaded to the app and automatically shared with the study doctors. The app sent automated prompts to the participants based on their blood pressure levels — to either repeat a studying or, if the studying was in a range that needed changes to their blood pressure medication, advised them to contact their doctor in the trial. The doctors then advised participants via phone or video call about how to adjust their medication to make sure their blood pressure remained below 140/90 mm Hg.

The remaining half of the participants received usual postpartum care, which, in the U.K., involves an office visit with the family physician or midwife 5-10 days after delivery and another at 6-8 weeks after giving birth.

"The trial suggests the timing of this second appointment may miss a critical window for early blood pressure optimization," Leeson said. "While this visit includes a blood pressure examination and participants are likely to be on blood pressure medication until their blood pressure is back in a normal range, their blood pressure will not be as carefully monitored and medication will not be as tightly adjusted as in the intervention group of the trial."

The trial results found:

• Nine months after delivery, the women in the intervention group had an average clinic blood pressure of 126/82 mm Hg, compared to 131/86 mm Hg for the women who received usual care.
• This long-term reduction in blood pressure was seen even though 70% of the women in both groups no longer needed high blood pressure medication by around six weeks after delivery. Participants in the intervention group had a median duration of treatment with anti-hypertensive medication of 39 days.
• The effect on lowering high blood pressure persisted for eight to nine months after participants stopped taking high blood pressure medication.
• Fewer women who received the intervention needed to go back into the hospital in the first three weeks after delivery as a result of high blood pressure.

"We were surprised by the size and consistency of the blood pressure reduction in the women who received the intervention. The benefits started to emerge within the first week or two after pregnancy, and the effect on blood pressure persisted after the medication was stopped," Leeson said.

"A 5-10 mm Hg reduction in blood pressure is typically associated with a 20% reduction in longer-term cardiovascular risk," he added. "If the reduction in blood pressure we observed at nine months is sustained long-term, this could slow progression to needing treatment for hypertension by an average of up to a decade."

Approximately 90% of participants agreed to have the researchers also perform cardiac magnetic resonance imaging and echocardiography on them at nine months postpartum. Women who had received the tighter blood pressure control after delivery showed clear improvements in the structure and function of the heart compared to women who had usual care.

Study details and background:

• Approximately 80% of the participants were white women, with an average age of 33 years.
• Approximately 65% of the study participants had just completed their 1st pregnancy, 30% had completed their second pregnancy and 5% had completed their 3rd pregnancy.

Study limitations included that the study was conducted at a single research center, meaning that the intervention may need to be modified before being repeated at multiple centers, and that the research team delivering the study intervention knew who had the self-monitoring devices, which may bias results. To overcome this potential for bias, the researchers ensured that blood pressure measurements were digitally collected by the participants' 24-hour blood pressure machines, which downloaded measurements and added them to the research database. This method was independent of the study team and mothers, and those who conducted the analysis were blinded to how the home blood pressure monitoring devices were allocated, Leeson said.

Future work will involve replicating the study in more racially and ethnically diverse patient populations in the U.K., identifying the optimal way to provide care after pregnancy and exploring the potential mechanisms of cardiac remodeling that may underpin the long-term lowering of blood pressure, Leeson said.

The 2017 ACC/AHA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults classifies stage 1 hypertension as having clinic top and bottom numbers greater than or equal to 130/80 mm Hg and stage 2 hypertension as having top and bottom numbers greater than or equal to 140/90 mm Hg.

Health- and fitness-conscious individuals worldwide opt for artificially sweetened beverages (ASBs) over their sugar-sweetened counterparts (SSBs), but the health advantages of ASBs remain debated within the scientific community. In a accurate umbrella review published in the journal Advantages in Nutrition, researchers examined the results of previous systematic reviews and meta-analyses to verify the credibility of medical and ASB-industry-funded research to evaluate whether AIBs truly meet the health gains that their manufacturers market. Their findings from 11 meta-analyses and seven systematic reviews indicate that frequent ASB consumption can lead to a higher risk of obesity, all-cause mortality, hypertension, type 2 diabetes (T2D), and cardiovascular disease (CBD), contrary to current consumer belief.

Review: Artificially Sweetened Beverages and Health Outcomes: An Umbrella Review. Image Credit: VTT Studio / Shutterstock

What are AIBs?

Artificially sweetened beverages (ASBs) are beverages containing sucrose-replacing sweeteners, including saccharin, sucralose, neotame, and advantame. Since they contain little to no conventional sugar (sucrose), they have little calorific value and are marketed as healthier alternatives to traditional sugar-sweetened beverages (SSBs). These drinks are trendy amongst health- and fitness-minded individuals and those overweight or obese based on the assumption that fewer calories, all else being equal, is better than more.

Recent medical research has challenged these assumptions, with a growing body of literature suggesting that ASBs may be linked to rapid unwanted changes in the gut microbiome and associated with increased all-cause mortality risk. Alarmingly, some studies have reported ABSs as contributing to cancers and cardiovascular disease (CVD), while others have found no such association. These conflicting medical reports are further complicated by industry-funded research, most of which gives ASBs their approval as safe for human consumption.

Umbrella reviews are a novel class of reviews that summarize and evaluate the results of previous reviews and meta-analyses while also verifying the technical and scientific soundness of the methodology and analyses that led to those results. They present an ideal means of cutting through the fluff, especially when multiple scientific reports suggest starkly contradictory outcomes (healthy versus not healthy) of the same treatment (ASB consumption).

About the study

The present umbrella review aims to examine the certainty of claimed health outcomes due to ASBs and identify potential biases or inconsistencies in the literature. This review further evaluates the methodologies employed in previous reviews and meta-analyses both as a test for credibility and to inform future authors of the best practices to use when conducting ASB-health studies.

This study adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Data was collated from three publication repositories, PubMed, Embase, and the Web of Science, from their inception until 25 May 2022. Inclusion criteria comprised all systematic reviews, meta-analyses, cohort, and case-control studies testing the associations between ASBs and health. However, cross-sectional studies were excluded due to the inherent weakness of evidence the study design suffers from. Results from systematic reviews comprising mixed study designs (cross-sectional alongside others) were filtered to remove the cross-sectional results, with the remaining results reanalyzed.

Collated data included the first author's name, the year of study publication, PECO (population, exposure, comparison group, outcome), exposure and outcome variables, and effect sizes. Additionally, the funding source of studies, both the meta-analyses and their constituent publications, were recorded.

The A MeaSurement Tool to Assess systematic Reviews (AMSTAR) tool (specifically AMSTAR-2) was used to evaluate the methodological soundness of included studies. The tool comprises 16 items that guide researchers in verifying the quality of systematic reviews.

"1) use of PECO elements in the description of aims and methods of the review, 2) adherence to a well-developed study protocol, 3) justification of the selection of study designs, 4) use of a comprehensive literature search strategy, 5) study selection in duplicate, 6) data extraction in duplicate, 7) provide a list of excluded studies and justification, 8) description of included studies in adequate detail, 9) proper technique used to assess risk of bias of included studies, 10) reporting of the sources of funding of selected studies, 11) appropriate methods for statistical analyses of the meta-analysis, 12) results of risk of bias assessments were considered in meta-analyses, 13) results of risk of bias assessments were discussed, 14) the sources of statistical heterogeneity were discussed, and 15) publication bias was assessed and discussed."

A random-effects model using the lowest study-specific ASB consumption as a standardization parameter was used to estimate the average effects of each 'high-quality' systematic review to test the effects of inter-study heterogeneity. This was then compared to results from a fixed-effects model assuming a lack of inter-study heterogeneity. Inconsistency between studies was computed using I², a metric that presents the amount of variability in effect results due to heterogeneity rather than study sampling error. Egger's test was used to compute slight study effect bias.

Study findings

The initial repository sweep identified 7,218 publications, of which 68 met inclusion criteria following title and abstract screening—of these 68, full-text screening and the exclusion of cross-sectional studies resulted in seven systematic reviews and 11 meta-analyses reporting PECO that were included in the statistical pipeline.

Collectively, the included studies reported the associations between ASB consumption and 13 health outcomes. Of these, present study analyses revealed that high- and regular ASB consumption depicted a positive association with CVD risk, CVD-associated mortality, chronic kidney disease, obesity, all-cause mortality, hypertension, T2D, and pancreatic cancer. Following AMSTAR assessments of the studies reporting these findings, however, the association between ASBs and CVD-associated mortality, chronic kidney disease, and pancreatic cancer was found to be weak and inconclusive.

Dependable study results revealed that sucralose and saccharin used in most ASBs have a rapid and severely detrimental impact on the human cardiovascular system, impairing glucose tolerance in hitherto healthy adults following only two weeks of daily ASB consumption. Human and animal studies further showed that some artificial sweeteners stimulate immune inflammatory responses in the gut wall.

"Results obtained with the AMSTAR-2 tool indicate that most authors of systematic reviews are not making use of predefined study protocols, which may increase the risk of making unfounded decisions during all the stages of the systematic review. Furthermore, all reviews did not add information of the sources of funding of the literature reviewed. The Cochrane handbook for systematic reviews of intervention recommends to examine closely the conflicts of interest of lead and corresponding authors, based on information reported in the present or previous publications or even searching in additional databases."

Outstanding 12-month first-in-human data from Xeltis’ aXess hemodialysis vascular conduit trial presented at VEITHsymposium 2023

• aXess demonstrated exceptional patency rates and no infections to date

EINDHOVEN, The Netherlands – 17 November 2023, Xeltis, a leading developer of transformative implants that enable the natural creation of living and long-lasting vessels, announces outstanding 12-month data from its first-in-human (FIH) aXess vascular conduit trial (NCT04898153). The data was presented yesterday by Prof. Dr. Frans Moll at the 50^th Annual VEITHsymposium in New York.

At 12 months, 100% secondary patency, 78% primary assisted patency and 0% infections were observed in data from 20 patients implanted with the aXess conduit. These outstanding results represent a significant improvement over current standard of care. This performance builds on the very encouraging 6-month data presented in April 2023 at the Vascular Access Society Congress in Porto, Portugal. To date, more than 3500 dialysis sessions have been conducted across the six centers in Belgium, Italy, Latvia and Lithuania.

aXess is a restorative conduit which enables the creation of a new, long-term living vessel for hemodialysis vascular access. The aXess FIH trial is a single arm feasibility study in Europe evaluating the preliminary safety and performance of the aXess graft in subjects older than 18 years with end-stage renal disease and deemed unsuitable for fistula creation. Follow-up visits were conducted at regular intervals after the initial procedure, with study follow-up visits to be conducted for five years. A separate pivotal trial of aXess is underway, enrolling up to 110 patients across up to 25 sites in nine EU countries, with over 40 patients already implanted.

The full data were presented today by Prof. Dr. Frans Moll, Department of Vascular Surgery, University Medical Centre Utrecht, The Netherlands, in a presentation entitled: Novel Application Of Polymer Technology To Create Endogenous Tissue with Host Collagen And Endothelium Compatible With Flowing Blood: 1-Year Clinical Results Of The aXess Graft.

Professor Dr. Frans Moll, vascular surgeon and member of Xeltis’ Medical Advisory Board, said: “The 12-month data from the aXess FIH trial are highly encouraging, and continue to demonstrate the potential of the aXess vascular conduit to combine the early benefits of AVG, such as early cannulation and no maturation needed, with the long-term advantages of AVF, including better patency rates, a reduced need for intervention and low infection rates.”

Eliane Schutte, CEO of Xeltis commented: “The outstanding 12-month data from our FIH study highlights aXess’ potential to transform the field of vascular access as a whole by stopping the cycle of interventions and infections. These latest results, alongside the excellent progress in enrollment for our pivotal trial, brings us closer to bringing our breakthrough solution to hemodialysis patients worldwide.”

-End-

About Xeltis
Xeltis is a medtech company developing transformative implants that enable the natural creation of living and long-lasting vessels. Xeltis seeks to address the limitations of currently available options for the millions of people requiring hemodialysis access grafts or cardiovascular replacements every year. The Company’s proprietary endogenous tissue restoration (ETR) platform utilizes an advanced polymer implant which regenerates the patient’s own tissue before gradually being absorbed and leaving new, living and long-lasting vessels in place. Xeltis’ most advanced product currently under clinical development is aXess^TM, an implantable blood vessel for hemodialysis vascular access. Xeltis’ groundbreaking technology has high potential to be applied to other major vascular and cardiovascular diseases.

Xeltis is based in The Netherlands and the USA. Its investors include DaVita Venture Group, EQT Life Sciences, Kurma Partners, VI Partners, Ysios Capital, Grand Pharma Group, the European Innovation Council and Invest-NL, in addition to other public and private investors.

About VEITHsymposium
Now in its 50th year, VEITHsymposium provides vascular surgeons, interventional radiologists, interventional cardiologists and other vascular specialists with a unique and exciting format to learn the most current information about what is new and important in the treatment of vascular disease. The 5-day event features rapid-fire presentations from world renowned vascular specialists with emphasis on the latest advances, changing concepts in diagnosis and management, pressing controversies and new techniques.

Contacts
Xeltis
Eliane Schutte, CEO
Alexander Goemans, CFO
info@xeltis.com

ICR Consilium
Amber Fennell / Chris Welsh                         
+44 (0) 20 3709 5700
xeltis@consilium-comms.com

VEITHsymposium
Pauline T. Mayer
+1 (0) 631-8076335