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Press Releases

Take a look at a selection of our recent media coverage:

Higher CVD risk in patients with obstructive sleep apnoea taking beta-blockers

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.

Beta-blocker usage in patients with OSA

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.

Cardiovascular polypill added to WHO List of Essential Medicines

7th August 2023

The World Health Organization (WHO) has added a cardiovascular polypill, which includes acetylsalicylic acid, ramipril and atorvastatin, to its List of Essential Medicines.

Developed by the Spanish National Centre for Cardiovascular Research (CNIC) in conjunction with the Ferrer Foundation, the cardiovascular polypill has been proven to be effective in preventing cardiovascular events after a heart attack.

Oscar Pérez, chief marketing, market access and business development officer at Ferrer, said: ‘The inclusion of this therapeutic solution in the WHO‘s List of Essential Medicines confirms our aim to make a positive impact in society and is an important step in our mission to bring significant and differential value to people with cardiovascular disease.‘

The polypill is currently marketed in 25 countries and the feasibility of extending its distribution to additional territories, including the United States, is under analysis.

The WHO defines essential medicines as ‘those that satisfy the priority health care needs of a population. They are intended to be available in functioning health systems at all times, in appropriate dosage forms, of assured quality and at prices individuals and health systems can afford.‘

Polypill clinical efficacy

The effectiveness of the polypill has been established in a clinical study published in the New England Journal of Medicine (NEJM) in the summer of 2022. The trial examined the effectiveness of the polypill as a secondary preventative measure in patients who had experienced a myocardial infarction.

The primary outcome for the study was a composite of cardiovascular death, non-fatal type 1 myocardial infarction, non-fatal ischaemic stroke or urgent coronary revascularisation. The results showed that the primary outcome occurred in 9.5% of patients in the polypill group and 12.7% in the usual-care group (hazard ratio = 0.76, 95% CI 0.60 to 0.96, P<0.001 for noninferiority; P=0.02 for superiority).

Dr Valentín Fuster, principal investigator of the NEJM study, said: ‘The SECURE results showed, for the first time, that the cardiovascular polypill developed by the CNIC and Ferrer achieves clinically relevant reductions in recurrent cardiovascular events in patients who have suffered a myocardial infarction.‘

Will the approval of colchicine lead to a paradigm shift in CVD management?

6th July 2023

Colchicine is a drug traditionally used for an acute attack of gout, but its most recent FDA approval has seen it repurposed for the management of atherosclerotic cardiovascular disease. Clinical writer Rod Tucker considers the evidence and what this means for CVD management.

Most clinicians will be familiar with the use of the anti-inflammatory agent colchicine as a treatment for acute attacks of gout, which is surprising given the lack of good quality evidence for the drug. But, recent events have put the drug on the map for a different purpose.

In late June 2023, the US Food and Drug Administration approved colchicine 0.5 mg for use in patients with cardiovascular disease to reduce adverse cardiac events. But how did a relatively inexpensive and widely used drug suddenly assume an important role in the management of atherosclerotic cardiovascular disease?

The prevailing wisdom is that atherosclerosis is due to the accumulation of cholesterol within the intimal of arteries and necessitates lipid-lowering therapy. An alternative cause, first mooted in 1999, has, until recently, been largely ignored. However, emerging evidence now implies that inflammation, rather than hypercholesterolaemia, is a more important driver of atherosclerosis, hence the rationale for the use of anti-inflammatory agents such as colchicine.

Inflammation and atherosclerosis

The fact that inflammation has a significant role in the development of atherosclerosis arose following the publication of the CANTOS study with canakinumab, which targets the pro-inflammatory agent interleukin-1β. In the trial, the use of canakinumab significantly reduced the primary efficacy endpoint of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death compared to the placebo.

While CANTOS clearly showed how reducing a single inflammatory marker lowered the risk of adverse cardiac events, earlier research had strongly implicated that neutrophils played a part in atherosclerosis.

The possible role of neutrophils in heart disease has been recognised for some time. In 1989, researchers identified an enhanced neutrophil function in patients with ischaemic heart disease although just where neutrophils sat in the pathophysiology of atherosclerosis remained unclear.

It was evident from a study in 1994, that inflammation was present at the immediate site of an atherosclerotic plaque rupture or erosion, leading to speculation that inflammatory changes had a pivotal role in destabilising the fibrous cap of an atherosclerotic plaque, enhancing the risk of coronary thrombosis.

The link between inflammation and neutrophils finally became much more intelligible in 2002, when it was discovered that neutrophil infiltration was actively associated with acute coronary events. Acknowledging the importance of neutrophils in cardiovascular disease, researchers then wondered if a drug that could inhibit the function of neutrophils might be advantageous to patients with cardiovascular disease.

Colchicine works by blocking the assembly and polymerisation of microtubules. These microtubules have numerous roles within cells including maintenance of cell shape, intracellular trafficking, cytokine and chemokine secretion, cell migration and the regulation of ion channels and cell division. But one important consequence of preventing the formation of microtubules is interference with neutrophil adhesion and recruitment to inflamed tissue.

It therefore seemed possible that a drug such as colchicine, might prove invaluable in patients with atherosclerotic cardiovascular disease. Whether this theoretical effect would benefit patients in practice remained to be seen.

Colchicine in cardiovascular disease

The road to the current approval of colchicine in cardiovascular disease was a long one, and the earliest attempts were disappointing.

In a 1992 study, scientists explored the value of the drug at preventing restenosis in patients following angioplasty, although colchicine proved to be no more effective than placebo. Fast forward to 2013, a study among patients who had recently experienced a myocardial infarction found that a daily dose of colchicine 0.5 mg combined with statin therapy appeared to be effective for the secondary prevention of cardiovascular events in patients with stable coronary disease.

Over the next seven years, more positive findings rolled in. For example, the secondary preventative value of colchicine was replicated in a 2019 study. Additionally, colchicine reduced adverse outcomes, in patients with any evidence of coronary disease and in those following either a recent (six to 24 months) or a prior (two to longer than seven years) acute coronary syndrome.

Assimilating the results from available studies, a 2021 meta-analysis of randomised trials with low-dose colchicine (0.5 mg), concluded that the drug lowered the risk of MACE, myocardial infarction, stroke and the need for coronary revascularisation in a broad spectrum of patients with coronary disease.

Given that atherosclerotic cardiovascular disease is largely assumed to be a direct consequence of elevated cholesterol, how important is the presence of inflammation?

A recent analysis, published in The Lancet, directly addressed this question. Researchers turned to three major statins trials in patients with, or at high-risk of, atherosclerotic disease to analyse the relative importance of inflammation and hypercholesterolaemia. The findings were very clear: inflammation rather than elevated levels of LDL cholesterol was the stronger predictor of future risk for both cardiovascular events and death.

While the mainstay of cardiovascular disease management over the past 20 years has been predicated on the notion that hypercholesterolaemia is a major cause, recent data does indeed suggest that inflammation is actually a more relevant prognostic marker.

With cardiovascular diseases still the leading cause of global deaths, the approval of colchicine is recognition of the need for a paradigm shift in the care of patients with the disease, and this will hopefully make a greater impact on overall mortality.

Wine drinking associated with reduced risk of adverse cardiovascular outcomes

23rd June 2023

Wine drinking is linked to a lower risk of death from cardiovascular disease but also reduces the risk of developing both cardiovascular and coronary heart disease, according to the findings of a recent meta-analysis.

Previous studies have hinted that the polyphenolic content of wine confers a cardio-protective effect whereas consumption of spirits, increases the risk of ventricular arrhythmias. In fact, evidence points to a J-shaped relationship between wine consumption and vascular risk.

Whether these purported benefits of wine are influenced by potential confounders such as age, gender, smoking status and the duration of follow-up within studies is uncertain. For the present study published in the journal Nutrients, researchers undertook a meta-analysis to examine the association between wine consumption and cardiovascular outcomes and assessed if this association was influenced by personal and study factors. The researchers looked for studies in adults and where the reported outcomes were cardiovascular mortality, cardiovascular disease (CVD) and coronary heart disease (CHD).

Wine consumption and adverse CV outcomes

There were 25 studies with 1,443,245 subjects included in the final analysis.

Wine consumption was associated with a 24% reduced risk of CHD (relative risk, RR = 0.76, 95% CI 0.69 – 0.84). In addition, there were also significant reductions in the risk of CVD (RR = 0.83, 95% CI 0.70 – 0.98) and for cardiovascular mortality (RR = 0.73, 95% CI 0.59 – 0.90).

In a sensitivity analysis, these associations remained statistically significant. However, publication bias was evidence for the link between wine and CVD but not for either CHD or cardiovascular mortality.

In further analysis, the effects of participants’ mean age, the proportion of women in studies, the duration of follow-up or if whether individuals currently smoked, did not impact on the reported associations.

The researchers did caution that increasing wine consumption could be detrimental for patients who are vulnerable to alcohol due to age, medication or pathology. They also suggested that further research is required to differentiate the observed effects by the type of wine.

Colchicine receives FDA approval for cardiovascular disease

22nd June 2023

Colchicine has become the first anti-inflammatory agent to be approved by the US Food and Drug Administration (FDA) for the treatment of cardiovascular disease (CVD).

According to the Europe-based manufacturer, Agepha Pharma, the FDA has approved colchicine 0.5 mg as the first anti-inflammatory athero-protective cardiovascular treatment, for patients either with established CVD or with multiple risk factors for the disease.

While both inflammation and hypercholesterolaemia jointly contribute to atherothrombotic disease, an analysis published in The Lancet in 2023, found that in patients receiving statins, inflammation was a stronger predictor for risk of future cardiovascular events and death than cholesterol. Colchicine achieves a beneficial effect in CVD at the cellular level through several mechanisms that include inhibition of endothelial cell dysfunction and inflammation, smooth muscle cell proliferation and migration, macrophage chemotaxis, migration, adhesion and platelet activation. 

Colchicine in patients with CVD

Evidence that colchicine is effective in CVD comes from a large study published in the New England Journal of Medicine. Over 5,000 patients with chronic coronary disease were randomised to colchicine 0.5 mg daily or matching placebo. The primary endpoint for the trial was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischaemic stroke or ischaemia-driven coronary revascularisation.

After a median of 28.6 months, significantly fewer patients assigned to colchicine experienced a primary endpoint event (hazard ratio, HR = 0.69, 95% CI 0.57 – 0.83, p < 0.001). Other work has also revealed how colchicine is effective in patients with chronic coronary disease both prior to and following an acute coronary syndrome.

Commenting on the approval, Paul Ridker, a consultant for Agepha Pharma as well as professor of medicine at Harvard Medical School and director of the Centre for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, said: ‘Approval by the FDA of the first drug to target cardiovascular inflammation is an important step forward for the care of our patients.

‘To treat coronary disease effectively, cardiologists must aggressively reduce inflammation and cholesterol. For appropriate patients already taking a statin, adding the anti-inflammatory drug colchicine at a dose of 0.5 mg daily has been proven to significantly lower risks of recurrent heart attack and stroke.

Colchicine is formulated as a once-daily, continuous-use oral treatment for adults that can be used safely either alone or in combination with standard-of-care lipid-lowering medications to effectively reduce the risk of heart attack and stroke.

The manufacturer anticipates that it will be available for prescription in the US in the second half of 2023. Potential plans for gaining approval in the UK or EU are currently unknown.

Almost 100,000 excess cardiovascular deaths in England since the start of the pandemic

Almost 100,000 more people have died with cardiovascular disease in England than expected in the three years since the pandemic began, a new analysis from the British Heart Foundation (BHF) shows.

The data up to this month shows an average 500 additional deaths a week involving cardiovascular disease since the start of the pandemic.

A range of factors are likely to contribute to the figures, which came from the Office for Health Improvement and Disparities (OHID), including Covid-19 itself, extreme pressure on the NHS and disrupted healthcare as well as changing patient behaviour and worsening population health, the charity said.

It noted that the number of patients waiting for time-sensitive cardiac care was at a record high of nearly 390,000 at the end of April in England, while average ambulance response times for heart attacks and strokes have consistently been above 30 minutes since the beginning of 2022.

The analysis found at 96,540 excess deaths involving cardiovascular disease between March 2020 and May this year – more than any other disease group.

Rates also changed over time with Covid-19 infection driving high numbers of excess deaths involving cardiovascular disease in the first year where more than 50% of the higher than expected deaths occurred.

Excess deaths involving cardiovascular disease then dropped significantly in the second year of the pandemic before increasing again in year three by 13,000.

In the third year of the pandemic, the number of excess deaths involving cardiovascular disease outnumbered the number of deaths where cardiovascular disease was mentioned but where Covid-19 was the underlying cause by around 19,400 deaths, the BHF said.

Urgent cardiovascular disease crisis

The charity warned the UK Government must take charge of the increasingly urgent cardiovascular disease crisis.

Dr Charmaine Griffiths, BHF chief executive, said: ‘It is deeply troubling that so many more people with cardiovascular disease have lost their lives over the last three years. My heart goes out to every family who has endured the pain of losing a loved one, all too often in distressing circumstances.

‘For years now, it has been clear that we are firmly in the grip of a heart and stroke care emergency. If little changes, we could continue to see a sustained rise in death rates from cardiovascular conditions that undoes decades of scientific progress to reduce the number of people who die of a heart attack or stroke.’

Dr Sonya Babu-Narayan, associate medical director at the BHF and consultant cardiologist, said Covid-19 no longer fully explains the significant numbers of excess deaths involving cardiovascular disease.

‘Other major factors are likely contributing, including the extreme and unrelenting pressure on the NHS over the last few years.

This story was originally published by our sister publication Pulse.

UK Government launches major conditions strategy consultation

18th May 2023

Doctors are among those who have been asked to respond to a consultation ahead of the UK Government’s major conditions strategy set to publish later this year.

A call for evidence has been launched on how to prevent, diagnose, and manage six conditions that account for 60% of ill health and early deaths in England.

The online survey for individuals and organisations asks questions on what the priorities should be for cardiovascular disease – including stroke and diabetes – chronic respiratory diseases; dementia; and; musculoskeletal disorders. It will be open until the 27 June.

The Government said it wanted to see what impactful interventions can be adopted and scaled quickly – that is, in the next one to two years – how to improve outcomes for people with more than one condition and how to tackle gender, ethnic and geographical disparities, the evidence call said.

It will also look at how to best support those with multiple conditions, with one in four people having two or more of the major long-term conditions included in the strategy.

Ministers are particularly keen to hear from those who suffer from, care for or provide treatment to people who suffer from multiple long-term conditions as part of the consultation, as well as those working for the NHS, local government, voluntary and community sector.

For each major condition area, participants are asked to select up to three priorities: prevention, stopping or delaying progression, improving speed of diagnosis, improving urgent and emergency treatment, or improving non-urgent and long-term treatment and care.

Positive response

Plans for the major conditions strategy were first announced in January as being ‘critical’ to achieving the Government’s manifesto commitment of five extra years of healthy life expectancy by 2035, and to narrow the gap in healthy life expectancy by 2030.

Health and social care secretary Steve Barclay, said: ‘Patients often live with more than one major condition, so it’s vital that we do all we can to understand how best to manage their care.

‘I encourage patients, carers and healthcare professionals to contribute to our call for evidence so we can ensure our Major Conditions Strategy is as targeted and patient-focused as possible.’

Minister of state for social care Helen Whately added: ‘We want to hear from as many people as possible affected by these conditions in our call for evidence. It’ll help us join up care across the NHS and mean better treatment for millions of people.

‘It’s also really important that we hear from professionals working in areas like dementia or cancer too. Their frontline experience will be invaluable to make sure our strategy includes plans which will really work in practice.’

Samantha Benham-Hermetz, director of policy and public affairs at Alzheimer’s Research UK, said: ‘Since the previous dementia strategy expired in 2020, the number of people living with the condition in the UK, and the challenges they face every day, have only continued to grow.’

She added that promising new treatments for early dementia were in development. ‘Bringing these into routine use will be challenging, and the major conditions strategy presents a huge opportunity to address these challenges and transform our health system,’ she said.

Sarah Woolnough, chief executive of Asthma + Lung UK, said: ‘Lung conditions are the third biggest killer in the UK, but historically haven’t received the attention they deserve, so the major conditions strategy is a big opportunity to change that.’

The Government said the views and ideas gathered will inform the priorities, content and actions in the major conditions strategy, which it will be publishing later this year. It will also publish an interim report in the summer.

10-year cancer plan

The Government has also published a summary of responses to its call for evidence on priorities for the 10-year cancer plan.

Most agreement was on the need to get people diagnosed quicker which 90% of individuals and 74% of professionals and organisations said should be a key focus over the next decade.

Suggested interventions included funding to expand the GP workforce and tackle geographical disparities to help people be seen sooner and training for GPs to recognise a wider range of symptoms.

Some respondents also called for GPs to listen better to patient concerns and act sooner ‘moving away from a culture of watch and wait’ as well as greater use of self-referral and at home tests for diagnostics.

A version of this story was originally published by our sister publication Pulse.

Pregnancy hypertensive disorders linked to higher future risk of cardiovascular disease

24th February 2023

Pregnancy hypertensive disorders increase the longer term risk of cardiovascular diseases according to a results of a Mendelian analysis

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.

Rayes B et al. Association of Hypertensive Disorders of Pregnancy With Future Cardiovascular Disease. JAMA Netw Open. 2023

Depression and poor mental health linked to higher incidence of CVD in young adults

3rd February 2023

Both depression and poor mental health days in young adults are associated with a higher risk of premature cardiovascular disease

Depression and poor mental health among young adults is more likely to lead to premature cardiovascular disease (CVD) and suboptimal cardiovascular health according to the findings of a large study of US adults by US and UK researchers.

A worrying trend over the past 20 years is the observed increase in the prevalence of recognised cardiovascular disease risk factors e.g., obesity, physical inactivity and a poor diet, among younger individuals in developed countries. Moreover, though not considered as a traditional CVD risk factor, the American Heart Association accepts that depression should be considered as a risk factor for adverse outcomes in patients with acute coronary syndrome. But to what extent does the presence of depression or even poor mental health, affect the risk of CVD among younger adults was the subject of the current study.

Researchers used data from the behavioural risk factor surveillance system which includes a nationally representative sample of non-institutionalised adults. The system assesses health-related risk behaviours and chronic health conditions, based on an annual telephone survey. The research team collected data on self-reported depression and poor mental health days (PMHDs), as well as CVD and suboptimal cardiovascular (CV) health, based on recognised risk factors, e.g., smoking, physical inactivity. In addition, self-reported PMHDs were categorised as 0, 1 – 13 or 14 to 30.

Depression and risk of premature cardiovascular disease
In total, data were collected from 593,616 with a mean age of 34.7 years (50.3% male).

The prevalence of depression was 19.6% and 2.5% for CVD. The researchers calculated that those with depression had a much higher odds of CVD compared to those without the condition (odds ratio, OR = 2.32, 95% CI 2.13 – 2.51). There was also a graded increased risk of CVD, depending on the number of reported PMHDs rising from an odds ratio of 1.48 (1 to 13 days) to 2.29 (14 to 30 days). These estimates were unaffected by gender or individual’s status (rural or urban). Suboptimal cardiovascular health was also higher among those with depression (OR = 1.79) and a similar graded relationship observed based on the number of PMHDs.

The authors concluded that based on their findings, prioritising mental health might help to reduce CVD risk and improve cardiovascular health in young adults.

Kwapong YA et al. Association of Depression and Poor Mental Health With Cardiovascular Disease and Suboptimal Cardiovascular Health Among Young Adults in the United States. J Am Heart Assoc 2023

Olpasiran substantially reduces lipoprotein A levels in cardiovascular disease patients

17th November 2022

Olpasiran has been shown to significantly reduce levels of lipoprotein A in patients with atherosclerotic cardiovascular disease

The small interfering RNA olpasiran has been found to virtually eliminate lipoprotein A in patients with atherosclerotic cardiovascular disease according to the findings of a randomised, placebo-controlled trial by US researchers.

Lipoprotein A (LPA) is a large glycoprotein attached to a low-density lipoprotein-like particle, that is associated with a risk of coronary heart disease and stroke. Lipoprotein A is produced by the apo(a) gene and levels are genetically determined with higher levels increasing the risk of atherosclerotic disease via mechanisms associated with increased atherogenesis, inflammation, and thrombosis.  Despite this known link and therefore risk of cardiovascular disease, there are currently no pharmacological therapies available to reduce its levels. Olpasiran is a small interfering molecule that interrupts the expression of the LPA gene by degrading the messenger RNA that encodes the apo(a) protein. In a preclinical study with mice, olpasiran reduced LPA concentrations by 80% from baseline for 5 – 8 weeks after administration of a single dose. Based on these findings, the US researchers undertook the Olpasiran Trials of Cardiovascular Events and Lipoprotein[a] Reduction–Dose Finding Study to assess the efficacy and safety of repeated administration of the product.

Individuals aged 18 to 80 with serum LPA levels higher than 150nmol/L and a history of atherosclerotic cardiovascular disease were included. These participants were randomised 1:1:1: 1:1 to receive four doses of olpasiran administered subcutaneously (10 mg, 75 mg, 225 mg every 12 weeks) and 225 mg every 24 weeks or matching placebo, for a period of 48 weeks. The primary endpoint was the percentage change in the LPA concentration from baseline to week 36 whereas the secondary outcome was the change at the end of the trial.

Olpasiran and Lipoprotein A levels

A total of 281 participants with a mean age of 61.9 years (32% female) were enrolled and randomised to one of the five arms (between 54 and 58 per arm). The overall median baseline LPA level was 260.3 nmol/L and 88% of participants were taking a statin and 23% a proprotein convertase subtilisinkexin type 9 (PCSK9) inhibitor.

At week 36, the LPA level increased by 3.6% in the placebo group but was significantly reduced in each of the active treatment arms. For example, the placebo-adjusted change in the 10 mg group was -70.5%, -97.4% in the 75 mg group and -101.1% in the 225 mg group and -100.5% in the 225 mg arm when administered every 24 weeks (p < 0.001 for all comparisons with the baseline value).

In addition, LDL cholesterol levels were also reduced with placebo-adjusted reductions ranging from -22.6% to -24.8%.

Adverse effects were generally similar across the groups.

The authors concluded that olpasiran significantly reduced lipoprotein(a) concentrations in patients with established atherosclerotic cardiovascular disease and called for future trials to assess the impact of treatment on cardiovascular disease.

O’Donoghue ML et al. Small Interfering RNA to Reduce Lipoprotein(a) in Cardiovascular Disease. N Eng J Med 2022