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Take a look at a selection of our recent media coverage:
25th July 2024
The UK’s medicines regulator has approved the use of semaglutide (brand name Wegovy) for cardiovascular prevention in obese and overweight patients with established cardiovascular disease (CVD).
The Medicines and Healthcare products Regulatory Agency (MHRA) granted the authorisation on Tuesday this week, making it the first weight loss drug to be prescribed as a preventative treatment for cardiovascular events.
The drug, supplied by Novo Nordisk, is already approved and recommended by the National Institute for Health and Care Excellence for use as a treatment for obesity, alongside lifestyle changes and support.
It can now be used to reduce the risk of overweight and obese adults suffering events such as cardiovascular death, non-fatal heart attacks and non-fatal strokes, in people with established cardiovascular disease and a body mass index (BMI) higher or equal to 27 kg/m2.
The MHRA has granted this authorisation based on data from a clinical trial which found that semaglutide reduces the incidence of major adverse cardiovascular events (MACE) by 20% when compared with a placebo.
There were over 17,600 participants in the multi-national, double-blind trial who were randomly assigned either Wegovy or a placebo.
Novo Nordisk first revealed headline figures from this study a year ago, with full results since published in the New England Journal of Medicine.
At the time, the company said it expected to file for regulatory approvals for a label indication expansion of semaglutide 2.4mg during 2023.
MHRA deputy director of innovative medicines Shirley Hopper said the safety of Wegovy will be kept ‘under close review’ but that the MHRA is ‘assured that the appropriate regulatory standards of safety, quality and effectiveness for the approval of this medicine have been met.
‘This treatment option that prevents heart disease and strokes is an important step forward in tackling the serious health consequences of obesity.’
Professor John Wilding, professor in the department of cardiovascular medicine at the University of Liverpool, said the approval is ‘good news’ based on evidence from the trial.
He said: ‘Semaglutide is already approved for treatment of obesity, but despite a favourable NICE appraisal since 2023, many people living with obesity in England and Wales are still unable to access this treatment due to funding restrictions and limited availability of NHS services for the treatment of obesity.
‘It is hoped that this new widened indication will help funders of services to understand the benefits of treatment for people living with obesity, and provide appropriate support for clinical services to provide treatment.’
Dr Martin White, associate professor in metabolic medicine at the University of Surrey, said that data from the trial also showed that there was ‘no difference in cardiovascular outcomes in those who did or did not achieve 5% weight loss’ after 20 weeks of semaglutide.
‘This hints that weight loss per se may not be a crucial factor, but any benefit may instead relate to benefits on blood pressure, glucose and body inflammation,’ he suggested.
Semaglutide, which is a GLP-1 receptor agonist, was launched on the NHS as a weight-loss drug in September.
The drug is available via specialist NHS weight management services for people who meet NICE criteria, or privately through a registered healthcare professional, but has been in short supply due to global demand.
A recent study indicated that weight loss in patients on semaglutide can be sustained for up to four years and that the drug can cut CVD risk.
And further research has shown that semaglutide could be beneficial in helping to treat patients with type 2 diabetes and obesity-related heart failure.
A version of this article was originally published by our sister publication Pulse.
9th July 2024
Professor Mona Bafadhel tells Katherine Price about developing a new tool that has identified less obvious yet crucial cardiovascular disease risk indicators such as chronic obstructive pulmonary disease. She hopes the tool will impact health inequalities by better predicting at-risk individuals and ensuring previously under-detected populations can access preventative therapies.
Professor Mona Bafadhel is the chair of respiratory medicine at King’s College London and director of the King’s Centre for Lung Health. Her work on chronic obstructive pulmonary disease (COPD) has recently led to her working with colleagues across King’s College London and the Universities of Oxford, Nottingham, Bristol and Edinburgh to support the development of a new cardiovascular disease(CVD) predictive calculator.
COPD is the third leading cause of death worldwide, causing more than three million deaths in 2019. Nearly 90% of deaths in patients under the age of 70 occur in low- and middle-income countries, and it’s estimated that in the UK, at least 4.9% of people over the age of 40 have COPD. By 2050, it’s predicted that global COPD prevalence will approach 600 million cases and become the leading cause of death globally. ‘[This] is an important group of patients,’ stresses Professor Bafadhel.
Among COPD patients, cause of death is often CVD, Professor Bafadhel explains. She and colleague Dr Richard Russell, head of department of the Peter Gorer Department of Immunobiology, were aware of the association between COPD and CVD based on their clinical experience and an increasing body of evidence. However, they wanted to understand more about the link between the two.
CVD is also a leading cause of death globally, responsible for an estimated 17.9 million deaths in 2019. Research into risk factors is abundant, but the tools available in clinical practice to score cardiovascular risk were unable to offer much insight into the CVD risk in a patient with COPD.
‘Indeed, it appears that current risk tools were underestimating the actual cardiovascular risk associated with patients with COPD,’ adds Professor Bafadhel.
The duo liaised with Professor Julia Hippisley-Cox from the University of Oxford and Carol Coupland from the University of Nottingham and others, who designed three iterations of QRISK – the CVD risk score that has been used across the NHS since 2009. It involves measuring patients’ blood pressure, age and medical history to identify those at high risk of developing CVD.
However, even QRISK3 does not capture several conditions that have recently been associated with increased CVD risk, including COPD, meaning it will potentially underestimate risk in these groups, who may subsequently not be offered beneficial interventions.
The new research, utilising several UK primary care databases to assess a cohort of more than 16.5 million UK citizens for derivation and validation of the algorithm, led to the development of QRISK4 or QR4, which showed that COPD was indeed a risk factor. In fact, QR4 outperformed three widely used international CVD scoring models, including QR3, due to the size and validity of the data, accurately identifying more high-risk patients.
‘The accuracy required has to be very vigorous with regard to validation tools and replication models,’ explains Professor Bafadhel. ‘It took a rigorous amount of work as standard because my collaborators Julia and Carol have experience of getting this into patient practice with QRISKs 1, 2 and 3, so we were guided and as sure as we can be that we were doing it even more rigorously for QR4.’
Like QR3, QR4 – if approved – would be a free-to-access web platform into which clinicians can enter details about patient health to generate a percentage risk of them developing CVD in 10 years’ time. Thresholds are also offered to inform clinicians as to when preventative treatment should be offered.
The difference is the inclusion of seven new risk factors. In addition to COPD, this includes learning disabilities, Down syndrome, four cancer types (blood, lung, oral and brain), pre-eclampsia and postnatal depression. While risk factors such as smoking and high cholesterol are well-recognised, this latest research identifies less obvious yet crucial risk indicators and highlights how other significant conditions impact on heart health.
Not only was an increased risk of severe cardiovascular events in patients with COPD identified, but the greatest effect was seen in females – a surprise for Professor Bafadhel.
Evidence previously suggested that COPD most commonly affected men, but more women appear to have COPD than first thought. What’s more, ‘it’s clear actually that women [with COPD] have more susceptibility to cardiovascular risk,’ Professor Bafadhel says, stressing that clinicians need to consider COPD as a diagnosis and confirm it with spirometry, especially in women, to mitigate these cardiovascular risks.
The risk was also highest in younger patients with COPD, which, for Professor Bafadhel, was another sign that conditions such as COPD need to be diagnosed earlier.
Ultimately, the research underlines the importance of prescribing therapies that reduce CVD risk, including optimising inhaled therapies, to reduce mortality.
By integrating these seven risk factors into the QR4 model, the researchers were able to develop a more nuanced and comprehensive tool for predicting CVD, ensuring preventative strategies are more personalised, inclusive and cater to the needs of a broader and more diverse population. It also provides clinicians with the clearest picture yet of individuals’ risk of developing heart and circulatory diseases.
Although the QR4 is based on UK population data, Professor Bafadhel hopes that other countries can use the research and their own population data to assess their own algorithms and tools. For countries with fewer resources, she says available tools can be used, mindful that the data may not be population relevant.
The hope is that, by providing a more accurate CVD risk estimation, QR4 should lead to significant improvements in health outcomes, particularly among populations whose risk may have previously been under-detected. If implemented, it is estimated that optimising the care of COPD patients would save more than 2,500 lives a year in the UK and promote earlier recognition of both COPD and the associated cardiovascular risk.
Professor Bafadhel argues the most important impact of this research would be driving awareness of the interlinked risks of CVD and COPD across the multidisciplinary field, and of how that risk can be modified.
‘We just haven’t had enough investment and funding in [COPD]. People may not know what it is until it’s too late. We really do need to improve the global awareness of it,’ she says.
‘We need to diagnose COPD earlier and be familiar with what COPD is. We need to optimise COPD treatments, including all the available tools we have. And then we need to try and understand what causes that very close association to cardiovascular disease, and of course exacerbations.’
She also highlights the importance of preventing CVD, catastrophic events and deaths by optimising COPD pharmacological treatment as well as primary prevention.
The researchers anticipate that QR4 will supersede QR3, although there is currently no timeline for this. Nevertheless, the next five years are expected to be an exciting time in the COPD field that will further shape understanding of this debilitating condition, according to Professor Bafadhel.
While she and her colleagues are looking at platelets in patients with COPD, other multidisciplinary groups are investigating pulmonary lung-heart events in this group – research Professor Bafadhel hopes will reduce inequalities, raise standards and empower patients to ensure they get the best treatment they need, when they need it.
‘Gone are the days where we think we can’t do anything for a person with COPD,’ she says. ‘We now have multiple tools, from physiotherapy to inhaled treatments, to non-invasive and invasive surgery, and in the next few months, hopefully also biologics in COPD.’
24th June 2024
Women who experience perinatal depression have an increased risk of developing cardiovascular disease, a study has found.
Researchers from the Karolinska Institutet in Sweden suggested that a history of perinatal depression could help predict cardiovascular disease.
Women who experience perinatal depression were found to have a 36% higher risk of developing cardiovascular disease and are more likely to develop high blood pressure, ischemic heart disease and heart failure in the 20 years after birth compared to women who have given birth without experiencing the condition.
The findings, published in the European Heart Journal, may help identify people at a higher risk of cardiovascular disease so that preventative measures can be taken to reduce the risk, the researchers said.
Perinatal depression can be experienced during or after pregnancy and is thought to affect one in five women who give birth worldwide. While major (non-perinatal) depression has consistently been associated with cardiovascular disease in previous studies, the long-term risk after perinatal depression is unknown.
Using data from the Swedish Medical Birth Register, the researchers analysed data from over 600,000 women who had given birth between 2001 and 2014. Of the women studied, 55,539 had been diagnosed with perinatal depression. All the women were followed up through to 2020 and assessed for cardiovascular disease.
The researchers found that women with perinatal depression were at a greater risk of developing heart disease, particularly high blood pressure, ischemic heart disease and heart failure.
Among the women with perinatal depression, 6.4% developed cardiovascular disease compared to 3.7% of women who had not suffered from it. Their risk of high blood pressure was around 50%, the risk of ischemic heart disease around 37%, and the risk of heart failure around 36% higher.
Dr Emma Bränn PhD, a postdoctoral researcher at the Karolinska Institute in Sweden, said: ‘This study adds to the established health risks of perinatal depression. Our findings provide more reason for ensuring maternal care is holistic, with equal attention on both physical and mental health.’
The researchers said it was unclear how perinatal depression leads to cardiovascular disease. Analysis of the sisters of women with the condition highlighted that they had a 20% higher risk of cardiac disease, suggesting there may be a genetic component to the findings.
Dr Bränn explained: ‘The slightly lower difference in risk between sisters suggests that there could be genetic or familial factors partly involved. There could also be other factors involved, as is the case for the link between other forms of depression and cardiovascular disease. These include alterations in the immune system, oxidative stress and lifestyle changes implicated in major depression.’
She added: ‘We need to do more research to understand this so that we can find the best ways to prevent depression and lower the risk of cardiovascular disease.’
A version of this article was originally published by our sister publication Nursing in Practice.
20th June 2024
Weight loss in patients taking semaglutide can be sustained for up to four years, according to results from the SELECT study presented at the European Congress on Obesity and published in the journal Nature Medicine.
A second as-yet-unpublished analysis from the same trial, also presented at the conference, found semaglutide delivered cardiovascular benefits irrespective of starting weight or amount of weight lost.
It follows a report last year that adults with overweight or obesity but not diabetes taking semaglutide for more than three years had a 20% lower risk of heart attack, stroke, or death due to cardiovascular disease.
Now, the updated analysis by UK researchers of the participants, who had already had a heart attack, stroke or had peripheral artery disease, suggests that even those with relatively mild levels of obesity, or those who only lose modest amount of weight, may have improved cardiovascular outcome.
Both findings have potential implications for current UK practice, experts noted.
Sustained weight loss was seen for men and women and across all races, ages and body sizes, the researchers reported, for what is the longest trial of the drug for this purpose to date.
In all, weight loss continued to Week 65 and then plateaued for four years, with participants’ losing on average 10.2% of their body weight and 7.7cm from their waistline, compared with 1.5% and 1.3cm respectively in the placebo group, the study found.
Study author Professor Donna Ryan, from Pennington Biomedical Research Centre in Louisiana, US, said: ‘This degree of weight loss in such a large and diverse population suggests that it may be possible to impact the public health burden of multiple obesity-related illnesses.
‘While our trial focused on cardiovascular events, many other chronic diseases including several types of cancer, osteoarthritis and anxiety and depression would benefit from effective weight management.’
Professor John Deanfield, professor of cardiology at University College London and consultant cardiologist at the Barts Heart Centre, London, UK, carried out the analysis on cardiovascular risk. He said there were important clinical implications for those with existing cardiovascular disease but cautioned against extrapolating the data more widely because it was not a primary prevention trial.
‘Around half of the patients that I see in my cardiovascular practice have levels of weight equivalent to those in the SELECT trial and are likely to derive benefit from taking semaglutide on top of their usual level of guideline directed care,’ he said.
‘Our findings show that the magnitude of this treatment effect with semaglutide is independent of the amount of weight lost, suggesting that the drug has other actions which lower cardiovascular risk beyond reducing unhealthy body fat.’
This could include positive impacts on blood sugar, blood pressure, or inflammation, as well as direct effects on the heart muscle and blood vessels, he said.
Professor Bryan Williams, chief scientific and medical officer at the British Heart Foundation, said it was important both that longer-term use of this approach for the treatment of obesity appears safe and that treatment is reported to significantly reduce the risk of death from heart diseases.
‘The latter confirms what we have long suspected, notably, that the increase in the risk of a number of cardiovascular diseases associated with obesity will be reversed is weight is reduced,’ he said.
‘This is likely to relate to a number of mechanisms, including improved blood fat profiles, lower blood pressure, less diabetes and less inflammation related to all of the above.’
He said a lot had been made of the potential benefit ‘beyond weight loss’ but in his view it was ‘all likely to be due to the reversal of the abnormal and damaging biology of obesity by reversing the weight gain’.
Professor Tricia Tan, professor of metabolic medicine and endocrinology at Imperial College London, said it suggested that NICE guidelines needed to be updated to increase funding for treatment up to four years or more.
‘Secondly, we also need proper funding from the NHS to implement the specialist clinics necessary for us to effectively deliver these life-saving and cost-effective medications,’ she added.
A version of this article was originally published by our sister publication Pulse.
17th February 2024
Speaking at Hospital Healthcare Europe’s Clinical Excellence in Cardiovascular Care event, Dr Rebecca Dobson discussed the need and demand for cardio-oncology services, how they’ve developed over time and the current state of play in this evolving field, as well as providing an overview of cardio-toxicity.
A decade or two ago, there was no such thing as cardio-oncology, and Dr Rebecca Dobson, consultant cardiologist specialising in imaging and cardio-oncology at Liverpool Heart and Chest Hospital and the Clatterbridge Cancer Centre, says things have ‘progressed somewhat from the days when all you were interested in was an ejection fraction’.
In fact, specialists like Dr Dobson – who also heads up her regional cardio-oncology service – now combine their wide-ranging cardiology expertise with close multidisciplinary working to allow cancer patients to receive the best possible treatments safely and minimise cancer therapy-related cardio-toxicity across the entire continuum of cancer care.
For a long time, everyone’s known that certain cancer therapies can affect the heart and, traditionally, these patients have been seen in heart failure clinics because we were looking for left ventricular systolic dysfunction.
But as the global burden of cancer has increased, and the treatments that we use to treat these cancers have increased, we’re seeing more and more patients with cancer who are exposed to more and more potentially cardio-toxic therapies, who would then potentially require the input of a cardiologist to maximise their cardiac health.
Previously, if a patient had cancer and was treated with cardio-toxic treatment, unfortunately, their outlook would have been relatively poor and a cardiologist would very rarely have to get involved with that patient’s treatment. Whereas now patients are living a lot longer with the effects of the cancer therapies.
And I think this is a real testament to the advances within oncology – the field is advancing at a really rapid pace, which is great for patients from a cancer point of view but it has important implications from a cardiology point of view.
What we don’t want to do with patients is cure their cancer and forget about their heart because it would be a real tragedy to cure someone’s cancer and then they end up having an avoidable cardio-toxicity.
It’s really important that we think about these patients’ cardiovascular health, and I think in the past, as cardiologists we’ve often almost shied away from patients with cancer. And I think we’ve probably done some of our patients a bit of a disservice because there is a lot we can do, and we need a rapid response service so that we can see these patients quickly.
I think a lot of patients worry that when they come to a cardio-oncology clinic, that we’re going to put up barriers and say, ‘you can’t have your cancer therapy’. And sometimes we do have to do that, but it’s actually quite rare. Far more often, we can facilitate the necessary cancer therapy by optimising the cardiac side of things.
Then at the other end of the spectrum, we look after patients who have been happily cured of their cancer, but who are at risk of late effects. So, these will be, perhaps, children or young adults who’ve had cancer at a young age and had lots of cardio-toxic therapy, but who are living with that increased risk for the rest of their lives.
These are the patients that we really don’t want to lose track of – they need to stay on someone’s radar so that we can screen them at regular intervals and pick up any issues at the earliest possible point.
One of the service fundamentals, I would say, is that we provide prompt cardiology input. At the moment, the way we’ve set our service up means we can see patients within a week to two weeks, so it’s a very responsive service. There’s lots of moving patients around to try and make sure that the most urgent patients get seen most quickly.
It also has to be based upon collaborative, multidisciplinary working. There is no point me sitting in my hospital at Liverpool Heart and Chest doing my cardiac thing with the patients and not talking to the oncologist who’s three miles up the road. It’s all about efficient communication with the oncologists, with the surgeons, anaesthetists, whoever it is who’s involved in that patient’s care. It is a truly multidisciplinary specialty, and I think it has to be because these are complicated patients and the last thing we want to do is make a decision that denies someone that a potentially life-saving cancer therapy.
I’d like to think that we offer a really holistic approach to patient care. And I say that with a smile on my face as a cardiologist because I know we’re not known for that – cardiologists will often focus on the heart and nothing but the heart. And I think these patients have such a lot going on with them, it’s really important that we recognise that within the service and work with other specialties to make sure we treat all of the patient and not just their heart.
Traditionally, cardiologists and oncologists have not worked closely together; we speak different languages. Certainly, when I when I first started in this subspecialty, I had no idea what a TKI was or what CHOP meant. And similarly, cardiologists have their own language talking about DAPT and TAVI and GLS. It’s really important that we try and understand where each other is coming from, understand clinical priorities, and have that collaborative approach to bridge the gap between the two specialties.
I’d recommend reading the 2022 ESC guidelines on cardio-oncology. It’s a really comprehensive document that covers lots of different types of cardio-toxicity.
It also includes a diagram that illustrates quite nicely the role of cardio-oncology care pathway. It’s important that we see patients at the beginning of their diagnosis, we follow them through their treatment, and we follow them up in the long term.
The diagram really illustrates the importance of risk stratifying patients at baseline and tailoring their cardio-oncology input accordingly.
I set up the service in 2019 and at that point, we were doing two cardio-oncology clinics a month. Now we’re running two and a half clinics a week and are looking to increase that further because the demand is there.
I also do a weekly ward round at Clatterbridge Cancer Centre, our local cancer hospital, which provides really useful input to the oncologists and radiotherapists there for inpatients with cancer who have a cardiac issue like atrial fibrillation or high blood pressure.
We run four weekly cardio-oncology echo lists and a weekly cardio-oncology MDT, which we do virtually and that’s probably the most important part of the service. Any patient who is particularly complex, where we’ve got important clinical decisions to make, will come through our MDT, and that will always have oncology, cardiology, radiology and usually cardiothoracic surgical representation.
We’ve recently taken over surveillance and management of all the region’s carcinoid heart disease patients. We’ve set up immunotherapy baseline screening programme so we can try and detect cardio-toxicity at an early stage. And we’ve worked with the radiotherapists at Clatterbridge to educate them and enable them to do their own cardiac monitoring for patients with cardiac devices when they’re receiving radiotherapy.
We’re quite busy, and we’re getting busier all the time, which is why we’re looking to bring in a cardio-oncology nurse specialist as soon as possible. We’re going to be running a physiologist-led echo clinic for those patients that don’t need to see a cardiologist. And we are also looking to improve our baseline ECG review for patients who are receiving immunotherapy.
I could talk for days about this! In the past, we’ve always thought about left ventricular systolic dysfunction being what we mean when we say ‘cardio-toxicity’. Certainly, a lot of what I deal with is cardiac dysfunction or heart failure, but it’s not the only thing I deal with.
It’s a real broad church of different manifestations of cardio-toxicity, which I think is probably another reason why I really enjoy my job – it keeps me on my toes. The more I do in this field, the more I realise that I’ve got a lot to learn and I’m always coming across another cardio-toxicity with a different type of drug.
From a cardiac dysfunction point of view, the drugs that we worry about the most are anthracyclines, the anti-HER2 therapies like herceptin.
From an arrhythmia point of view, oncologists do use arsenic to treat some types of cancers, and arsenic and tyrosine kinase inhibitors (TKIs) are very good at causing atrial fibrillation and arrhythmias. And TKIs and mTOR inhibitors are the main offenders for causing hypertension.
For vascular toxicity, it’s usually the drugs that we use to treat bowel cancer so 5FU, which can cause coronary artery spasm, which can be incredibly dramatic. We’ve seen patients who’ve presented with the peri-arrest with ST elevation that’s all settled down as that spasm is released.
And myocarditis is usually caused by checkpoint inhibitors or immunotherapies, but there are other drugs that can do it as well.
Cardio-toxicity does not always occur at the beginning when someone has commenced on systemic anti-cancer therapy. Patients who present very acutely within hours or days of commencing their therapy, although they tend to have a very dramatic presentation, ironically, they seem to have the best prognosis. Everything usually settles down with some treatment and is reversible.
It’s the patients who present months to years after having their treatment, who can be most challenging. This is why it’s so important to take a proper medical history for all patients and think outside the box.
Keep an open mind and remember that cardio-toxicity has lots of manifestations but also has a very variable timescale. If you’ve got a patient with any of these cardiovascular problems, always think: are they a cancer patient? Have they had treatment? When was the treatment?
Demand for collaborative cardio-oncology services is only going to go in one direction and it’s not just for cardio-oncologists, either. All clinical cardiologists are going to see patients with cancer in their clinics, whether that’s valve clinics, percutaneous coronary intervention clinics, heart rhythm clinics or hypertension clinics, because, as I’ve said, cardio-toxicity is much broader than left ventricular systolic dysfunction.
ESC’s position paper on baseline cardiovascular risk assessment in cancer patients from a few years ago is a really useful document.
If we can identify patients at high risk of cardio-toxicity from the beginning, we can optimise things as much as possible. It’s really important that we work with the oncologist to persuade them to take a blood pressure, to do an ECG and to take a history at the beginning of cancer therapy so that we can focus our energies and resources on those that probably need us most.
The ESC guideline published in 2022 comes with a risk calculator. You can download the app onto your phone, and then you put in the patient’s variables: age, troponin, previous history, whatever it might be. Then it will tell you whether they’re low, medium, high or very high risk.
In terms of what that means for their cancer therapy, we will sometimes make a decision with the oncologist and the patient that their risk is too high to proceed with cancer therapy. These are usually patients who are not due to receive curative chemo. If the chemotherapy makes the difference between life and death and is potentially lifesaving then it would be unusual for us to say we can’t give it.
Usually, we will do everything in our power to enable the oncologist to give what they need. But there are certain circumstances where that wouldn’t be the case. For example, I’d be very reluctant for patients who’ve had coronary artery spasm with cardiac arrest to have more of the same chemo because we know that the risk of recurrence is significant. But that would be quite extreme and, as I say, we would work hard to enable the chemo or other treatment to continue.
Sometimes there might be two different treatment options with different risks and benefits. We’ll always bring the patient into that conversation and say, ‘look, we’ve got two different options from a cancer point of view, one is associated with a risk to your heart, the other isn’t’, and we’ll talk a bit about the risk and benefit from the cancer and cardiology sided, and then make that decision together.
Nobody should be making unilateral decisions about these patients; it should be a real collaborative, multidisciplinary approach.
The spring 2024 Clinical Excellence in Cardiovascular Care event will take place on 19 March, with Dr Rebecca Dobson as chair. Registrations for all members of the multidisciplinary team are now open.
16th February 2024
Patients who successfully reversed a type 2 diabetes diagnosis though lifestyle changes substantially reduced their cardiovascular disease (CVD) and chronic kidney disease (CKD) risk in the long term, a study has found.
Published in the journal Diabetologia, the results came from a large trial of almost 4,500 participants in which doctors were comparing an intensive lifestyle programme with standard diabetes education and support.
Taking no diabetes medications and having a HbA1c of less than 48 mmol/mol (6.5%) at a single point in time was classed as remission.
Overall, those who achieved remission through the lifestyle changes – in whichever group – had a 33% lower rate of CKD and a 40% lower rate of CVD.
But those who had the most intensive support were more likely to be in remission from their diabetes, with 12% meeting the criteria at least one follow-up and falling to 7% over time compared with around 2% in the regular support group.
Being in remission overall was significantly linked to changes in weight and risk factors over the years, the study found.
Average weight loss associated with remission was 7.3kg after one year and 4.5kg after four years.
There were also significantly greater improvements in HDL-cholesterol and fitness after one and four years, and significantly greater systolic blood pressure improvements after one year among participants with remission compared with those without remission, the team said.
The analysis also showed systolic blood pressure decreased more and HDL-cholesterol increased more among participants who achieved a greater duration of diabetes remission.
There was a dose-response relationship with those who had remission for at least four visits seeing the most impact, the researchers said.
Those taking part in the study – which ran between 2001 and 2016 – had a mean age of 59 years and on average were in the range of severe obesity.
It was noted that while 18% of participants achieved remission at some point during follow-up, the percentage of participants with current remission had decreased to 3% by the eighth year of the study.
The figures underline, the challenges of keeping weight off using lifestyle interventions, the researchers said.
But for those with at least four years of remission the risk of CKD and CVD was reduced by 55% and 49% respectively.
The analysis also noted participants with a short duration of diabetes, low starting HbA1c and a large magnitude of weight loss were most likely to experience remission.
Study lead Professor Edward Gregg, head of the School of Population Health, RCSI University of Medicine and Health Sciences in Dublin, said: ‘As the first intervention study to associate remission with reduction of diabetes-related complications, this is encouraging news for those who can achieve remission from type 2 diabetes.
‘While our study is also a reminder that maintenance of weight loss and remission is difficult, our findings suggests any success with remission is associated with later health benefits.’
Another recent study has found that regular bouts of moderate to vigorous physical activity can protect patients with type 2 diabetes from developing kidney disease.
A version of this article was originally published by our sister publication Pulse.
17th August 2023
JAK inhibitors are known to increase the risk of major adverse cardiovascular events when used in rheumatoid arthritis, but does this elevated risk also apply when this class of drugs is used in atopic eczema? Clinical writer Rod Tucker investigates.
Since the 1990s, the treatment of severe rheumatoid arthritis (RA) has centred on biologics such as tumour necrosis factor (TNF) inhibitors. However, a better understanding of cell signalling pathways and, in particular, intracellular signal transduction, led to the development of alternative therapies, one of which being oral Janus kinase (JAK) inhibitors. Several of these have been approved for use in RA since 2011.
What’s more, as JAK inhibitors disrupt intracellular signalling through a variety of cytokine and haematopoietic growth factor receptors, this mode of action suggests the drug class may have a much wider role in a number of immune-mediated inflammatory diseases. As such, approvals for JAK inhibitors in Crohn‘s disease, psoriasis and atopic eczema have been seen in recent years.
Despite their apparent effectiveness in RA, a recent post-marketing study has raised safety concerns over JAK inhibitors compared to TNF inhibitors. The Oral Rheumatoid Arthritis Trial (ORAL) was a randomised, post-authorisation, non-inferiority trial designed to evaluate the safety and efficacy of the JAK inhibitor tofacitinib compared to a TNF inhibitor such as etanercept or adalimumab. It focused on patients with RA who were aged 50 or older and had at least one additional cardiovascular risk factor.
The findings were somewhat disturbing. JAK inhibitor use led to a significantly higher incidence of both major adverse cardiovascular events (MACE) and cancers compared to a TNF inhibitor, even though the efficacies were broadly similar.
The ORAL trial served to highlight how JAK inhibitors may increase the risk of MACE when used in patients with RA who are already at an elevated risk due to their condition. Indeed, a meta-analysis of 24 studies with over 111,000 RA patients estimated a 50% higher risk of cardiovascular mortality.
So, with three JAK inhibitors (upadacitinib, baricitinib and abrocitinib) approved for atopic eczema, and representing an important and promising development for its treatment, should dermatologists be concerned over the risk of MACE when using this class of drugs?
Before considering whether JAK inhibitors might increase the risk of adverse cardiovascular sequelae in those with atopic eczema, its worth exploring whether atopic eczema, itself an inflammatory condition, is linked to a higher risk of MACE. After all, such a risk is theoretically possible, given the emerging evidence of the pivotal role of inflammation in the development and progression of both cardiac and vascular diseases.
The current evidence of an association between atopic eczema and MACE is equivocal. Some work, for instance, clearly demonstrates that atopic eczema is associated with increased risk of myocardial infarction compared to the general population. In contrast, another study found no such independent association in women.
Nevertheless, pooling data from several studies does suggest a positive relationship. For example, a 2018 meta-analysis of 15 studies, which included over 3.5 million participants, did show that atopic eczema was independently associated with an increased risk of stroke and myocardial infarction, especially in male subjects and those with more severe disease.
In addition, a recent Danish study, looked at what happened to patients over time following a diagnosis of atopic eczema. It included over 40,000 atopic eczema patients and an equal number of matched controls and found that adults were at a significantly higher risk of experiencing a subsequent cardiovascular disease.
Finally, a UK prospective study including 387,439 patients with atopic eczema followed for over five years, concluded that severe active atopic eczema was associated with an increased risk of cardiovascular outcomes.
While prospective studies are subject to confounding, Mendelian randomisation studies, are able to provide an estimate causality without the influence of confounders. One such study showed that asthma and atopic eczema were causal risk factors for heart failure and suggested that the underlying inflammatory nature of both diseases was a major contributory factor.
As ever, things are never that straightforward. In a recent bidirectional Mendelian randomisation study, it was found that there was no robust association between cardiovascular disease and atopic eczema.
In trying to establish if there was a higher risk of MACE in patients with atopic eczema prescribed a JAK inhibitor, researchers recently undertook a systematic review and meta-analysis. The findings were published in July 2023 in the British Journal of Dermatology and included phase 2b or 3 randomised controlled trials and controlled cohort studies.
The primary outcome was the occurrence of MACE, which the researchers defined as a composite of acute coronary syndrome (ACS), ischaemic stroke and CV death.
A total of 23 studies were included in the analysis. Very few cases of MACE were found, leading the researchers to suggest that JAK inhibitors may have little-to-no effect on the occurrence of MACE in patients with atopic eczema compared to placebo. However, they did add the caveat that the evidence was uncertain.
In addition, MACE generally occurred in patients at a high cardiovascular risk and not in the younger, healthy patients typically seen in routine clinical practice.
Further and reassuring evidence of the absence of a possible association with MACE comes from real-world studies on the use of JAK inhibitors in atopic eczema. There have been at least four such studies, none of which have identified any cases of MACE, even though some have been conducted in patients with more severe disease.
Although patients with atopic eczema may have a higher risk of MACE, this is more likely to occur either in those with severe disease or for patients at a greater risk of cardiovascular disease. Over time, pharmacovigilance data will no doubt shed further light on the level of risk associated with JAK inhibitors.
For now, the European Medicines Agency (EMA) issued advice in January 2023 on the use of JAK inhibitors in all chronic inflammatory disorders, including atopic eczema. This recommended avoiding against the use of a JAK inhibitor in those aged 65 years or above, in patients at an increased risk of major cardiovascular problems, smokers and individuals at a higher risk of cancer, unless there are no suitable alternatives.
For most patients with atopic eczema, JAK inhibitors represent a potentially game-changing addition to a dermatologist’s armamentarium for their treatment. Provided that clinicians heed the current safety guidance, those prescribed a JAK inhibitor for atopic eczema have much to gain but without the attendant risk of MACE.
16th August 2023
The use of beta-blockers is associated with an increased risk of cardiovascular disease (CVD) and a trend for a higher mortality risk among patients with obstructive sleep apnoea (OSA), according to the findings from a recent study.
Researchers from University College London School of Pharmacy found that the use of beta-blocker drugs in patients with OSA increases the five-year risk of mortality and adverse cardiovascular outcomes.
In the absence of real-world evidence, the study, published in The Lancet Regional Health – Europe, investigated the impact of beta-blocker use on all-cause mortality and adverse cardiovascular outcomes in patients with OSA.
For the purposes of their analysis, the researchers turned to IQVIA Medical Research Data – a nationwide database of primary care records in the UK that contains around 6% of the total UK population in 2015. The database includes demographic and lifestyle information such as smoking and alcohol consumption, medical diagnoses and procedures, together with prescribing information.
Included patients were adults aged over 18 who had a diagnosis of OSA in their medical records. The team then compared the treatment strategies of initiating oral beta-blockers versus not starting a beta-blocker in these patients.
The outcomes of interest were all-cause mortality or a diagnosis of CVD, defined as a composite event of angina, myocardial infarction, stroke/transient ischaemic attack, heart failure or atrial fibrillation.
A total of 37,581 patients met the eligibility criteria and were followed for a median of 4.1 years.
The five-year absolute risk of all-cause mortality and CVD outcomes were 4.9% and 13.0% among beta-blocker users, compared to 4.0% and 9.4% among non-beta-blocker users, respectively.
Commenting on these findings, study lead Dr Kenneth Man said: ‘Our study underscores the urgent need for further investigation into the relationship between beta-blockers and health outcomes in OSA patients.
‘Our hope is that this information will help medical professionals make more informed decisions when treating patients with OSA.‘
This extensive study is one of the few exploring the real-world implications of medical treatment in OSA patients. It emphasises the importance of careful and continued monitoring of these patients and encourages further investigation in this field.
Further studies are anticipated to confirm these findings and delve deeper into understanding the association between beta-blocker usage and patient outcomes. Until such studies are conducted, the medical community is urged to consider the potential risks highlighted by this research when treating patients with OSA.
25th April 2023
Psychological therapy that improves a patient’s depression could also reduce their risk of developing cardiovascular diseases in the future, according to new research.
In the first-of-its-kind study, published in the European Heart Journal, researchers retrospectively examined a cohort of 636,955 individuals who had completed the Improving Access to Psychological Therapy (IAPT) primary care programme for depression.
Individuals were free of cardiovascular disease (CVD) before entry into the IAPT and over 45 years of age, with a mean age of 55. Some 58.6% showed an improvement in their depression. Regression models then estimated the association between improvement of depression and the risk of subsequent CVD events.
In fully adjusted models, those whose depression symptoms improved after psychological therapy were 12% less likely to experience a cardiovascular event than those who did not, over an average three-year follow up.
Indeed, improving depression symptoms gave rise to a significant lowering in the risk of any new onset of CVD (hazard ratio, HR = 0.88, 95% CI 0.86 – 0.89). This was true for coronary heart disease (HR = 0.89), stroke (HR = 0.88) and all-cause mortality (HR = 0.81).
This reduction in CVD risk and risk of death from all causes was higher in those aged under 60, with 15% and 22% decreased risk respectively. Those over 60 years of age had a 5% decreased risk of developing CVD and 14% decreased risk of death from all other causes.
The authors suggest that management of depression with psychological therapies might therefore reduce the risk of subsequent CVD, but more research is needed to understand the causality of these associations.
Commenting on the study, lead author Celine El Baou, PhD candidate from UCL Psychology & Language Sciences, said: “The findings are important as they suggest that the benefits of psychological therapy may extend beyond mental health outcomes and to long-term physical health. They stress the importance of increasing access to psychological therapy to under-represented groups, for example minority ethnic groups who may be more at risk of experiencing cardiovascular disease.”
The authors also noted that previous studies have shown that people who experience depression are around 72% more likely to develop cardiovascular disease in their lifetime.
A study published earlier in 2023 also highlighted that depression and poor mental health among young adults is more likely to lead to premature CVD and suboptimal cardiovascular health. The researchers concluded that prioritising mental health might help to reduce CVD risk and improve cardiovascular health in young adults.
In 2021/22, 1.24 million referrals accessed the Improving Access to Psychological Therapies (IAPT) programme (now renamed NHS Talking Therapies for anxiety and depression) compared to 1.02 million the previous year, according to latest NHS Digital statistics.
24th February 2023
Women who experience pregnancy hypertensive disorders such as preeclampsia have a higher risk of developing cardiovascular disorders in the future according to the findings of a Mendelian randomisation analysis by UK and Dutch researchers.
Hypertensive disorders during pregnancy affect 8% to 10% of all pregnant women and can lead to serious complications including mortality. In fact, one systematic analysis revealed how 14% of maternal deaths were due to hypertensive disorders. Moreover, observational evidence suggests that having a pregnancy-related hypertensive disorder increases the risk of cardiovascular events in later life. Nevertheless, observational data cannot be used to determine a causal relationship due to potential confounding. However, a better study design that can determine whether such a relationship is causal is the use of Mendelian randomisation (MR). This approach uses the genetic risk of disease as a proxy for the disease itself and can be used to mitigate the effect of confounding, as the MR estimate can be used to interpret the effect of the exposure, in this case pregnancy-related hypertensive diseases, on the outcome of interest (cardiovascular disease).
In the current study, researchers used estimates of genetic association obtained from genome-wide association data, to examine the association between gestational hypertension and preeclampsia and the risk of subsequently developing coronary artery disease, ischaemic stroke, heart failure and atrial fibrillation. The team also employed mediation analysis based on multivariable MR, to consider the impact of potential mediators e.g., body mass index, systolic blood pressure etc, on any identified associations.
Pregnancy hypertensive disorders and future cardiovascular risk
For any genetically predicted hypertensive disorder, there was an elevated risk of developing coronary artery disease (Odds ratio, OR = 1.24, 95% CI 1.08 – 1.43, p = 0.02). The risk was also elevated when considering gestational hypertension (OR = 1.08, p = 0.04), preeclampsia or eclampsia (OR = 1.06, p = 0.03) and ischaemic stroke (OR = 1.27, P < 0.001). However, the risks were non-significant for both gestational hypertension and preeclampsia and there were also non-significant for both heart failure and atrial fibrillation.
In the mediation analysis, there was a partial attenuation of the overall risk for CAD after adjusting for systolic blood pressure (adjusted OR = 1.10 vs 1.24) and the presence of type 2 diabetes (adjusted OR = 1.16 vs 1.24).
The authors concluded that given their findings, the presence of pregnancy-related hypertensive disorders should be considered as risk factors for cardiovascular disease.
Citation
Rayes B et al. Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease. JAMA Netw Open. 2023
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