Digoxin benefits surpass beta-blockers for older AF patients and the NHS, study finds

6th February 2025

Switching from beta-blockers to digoxin as first line therapy for heart rate control in older patients with atrial fibrillation (AF) and symptoms of heart failure could produce a cost saving of over £100m a year for the NHS, a study has found.

AF accounted for more than 1% of the annual NHS budget, predominantly from hospital admissions, researchers wrote in the journal Heart.

The RAte control Therapy Evaluation in permanent Atrial Fibrillation (RATE-AF) study was a randomised, open-label trial embedded in the NHS that directly compared low-dose digoxin – usually used as second-line therapy – with the typical first-line approach of beta-blockers.

The trial initially randomised 160 older patients with permanent AF and symptoms of heart failure (mean age 76 years, 46% women).

Researchers previously reported no difference in the primary outcome of health-related quality of life in the physical activity domain between the groups at six months, however nearly all secondary outcomes favoured digoxin by 12 months, with better patient functional capacity and less evidence of cardiac strain.

There were lower rates of side effects, cardiovascular events and hospital admissions in those randomised to digoxin.

‘Digoxin significantly less costly‘

For this prespecified health economic analysis of the National Institute for Health and Care Research-funded trial, researchers assessed information from the 149 patients who had complete data and survived to 12 months follow-up.

The analysis found no significant effect on quality-adjusted life years (QALY) between groups, however treatment with digoxin was significantly less costly than therapy with beta-blockers, with a mean saving of £530.41 per patient per year.

‘This was principally due to substantially lower rates of adverse events, with less primary and secondary healthcare utilisation compared with beta-blocker therapy,’ the researchers reported.

Extrapolating the study findings to current prevalence and costs of AF in the NHS, suggested a potential cost saving of £102 million per year, which was equivalent to a 5.9% saving on the £1.7bn spent annually on AF, the study reported.

The researchers noted the cost of secondary care services, mainly inpatient care, was significantly lower in the digoxin arm, reflecting that these patients had substantially fewer serious adverse events (16 serious adverse events in 13 patients for digoxin vs 37 in 21 patients for beta-blockers) and fewer treatment-related adverse events (29 treatment-related adverse events in 20 patients for digoxin vs 142 in 51 patients for beta-blockers).

The mean total costs for secondary care were £8.88 per patient over 12 months in the digoxin group and £484.83 per patient in the beta-blocker group, with adjusted bootstrapped difference of –£518.04 per patient in favour of digoxin.

‘While likely applicable to similar healthcare settings outside the UK, further studies with formal economic evaluation are needed to address this key evidence gap and the implications for global management of patients with AF,’ the authors concluded.

‘Safe and cost-effective treatment‘

Corresponding author Professor Sue Jowett, deputy head of the Health Economics Unit at the University of Birmingham, said the study highlighted the importance of health economic assessments and the role they could play in delivering appropriate treatments.

‘At the usual £20,000 per QALY threshold, the probability of digoxin being cost-effective compared to beta-blockers was 94%, which could lead to substantial savings if the trial results were adopted more broadly in this population,’ she said.

Trial chief investigator Professor Dipak Kotecha, professor of cardiology at the University of Birmingham, and a consultant cardiologist specialising in cardiac imaging at University Hospitals Birmingham NHS Trust, said cardiac conditions such as AF and heart failure were expected to double in prevalence over the next few decades.

‘Despite being one of the oldest drugs in use for heart disease, this study confirms an important role for digoxin in the management of these patients, providing safe and cost-effective treatment,’ he said.

Last year, the European Society of Cardiology released new guidelines at its congress in London, including one dedicated to the management of AF.

The novelties of this AF guideline included the recommendation of the new CHA₂DS₂-VA score to assess thromboembolic risk when making decisions on initiating oral anticoagulation, which no longer includes gender.

Research digest: The impact of cancer diagnosis on heart failure medical therapy use

6th September 2024

Following a cancer diagnosis, patients with heart failure with reduced ejection fraction (HFrEF) are less likely to continue or maintain the use of guideline-directed medical therapies (GDMTs), according to a new longitudinal study.

Researchers from University College London Hospitals NHS Foundation Trust analysed data from patients with heart failure in UK Clinical Practice Research Datalink between 2005 and 2021. Based on diagnostic and prescription records, patients with probable HFrEF were selected, and trends in the use and dosing of GDMTs before and after receiving a new cancer diagnosis were analysed.

The researchers matched 4,890 HFrEF patients with incident cancer to controls without cancer. The majority of the participants were male (73.9%), and the mean age was 75.7 years.

Patients with cancer were found to be 51% more likely to have poor adherence to renin-angiotensin-system inhibitors (RASIs), 22% more likely to have poor adherence to beta-blockers and 31% more likely to have poor adherence to mineralocorticoid receptor antagonists (MRAs) compared to non-cancer controls (RASIs: OR = 1.51, 95% CI = 1.35–1.68; beta-blockers: OR = 1.22, 95% CI = 1.08–1.37; MRAs: OR = 1.31, 95% CI = 1.08–1.59).

Cancer patients are also less likely to continue taking the GDMTs over time, with 104% more likely to stop taking RASIs, 35% more likely to stop taking beta-blockers and 49% more likely to stop taking MRAs than non-cancer controls.

Titration doses for RASIs and beta-blockers were more likely to be reduced after a cancer diagnosis (OR = 1.69, 95% CI = 1.40–2.04 and OR = 1.31, 95% CI = 1.05–1.62, respectively). None of the patients started new heart medications or had their medication doses increased after a cancer diagnosis, the researchers noted.

The reduction, interruption or cessation of heart failure treatments has a potentially negative impact on cardiovascular outcomes, the researchers said, adding that ‘this issue is even more concerning if the [heart failure] patient eventually needs cardiotoxic cancer treatments’.

Since heart failure leads to increased hospitalisation, and mortality is higher in patients with poor adherence or persistence to GDMTs, the researchers have called for better medical management of heart failure after a cancer diagnosis.

They also highlighted the need for further research, including targeted strategies for heart failure treatment optimisation, patient and clinician education at the time of cancer diagnosis, and an increase in multidisciplinary working between cardiologists, oncologists, general practitioners, pharmacists and specialist nurses.

Reference
Ju, C et al. Use of heart failure medical therapy before and after a cancer diagnosis: A longitudinal study, ESC Heart Failure 2024; Jul 23: doi.org/10.1002/ehf2.14981.

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.