SGLT-2 inhibitors benefit heart failure regardless of diabetes, real-world study finds

27th December 2024

The sodium glucose cotransporter 2 (SGLT-2) inhibitors dapagliflozin and empagliflozin cut mortality in patients with heart failure with reduced ejection fraction whether or not patients have diabetes, a large real-world study has concluded.

The analysis of SGLT-2 inhibitor drugs in patients on a national Danish registry found they were associated with a 25% lower risk of all-cause mortality, ‘supporting their effectiveness in routine clinical practice’.

Reporting in the BMJ, the researchers examined outcomes in patients with heart failure aged over 45 years with left ventricular ejection fraction less than 40% between 2020 and 2023.

In their dataset, they reviewed 6,776 patients who started SGLT-2 inhibitors (79% on dapagliflozin, 21% prescribed empagliflozin) and 14,686 patients taking other standard-of-care heart failure drugs, while taking into account time since diagnosis and other baseline characteristics.

Around 70% of patients taking SGLT-2 inhibitors were men, with an average age of 71 years, and 20% of the cohort had type 2 diabetes.

The results showed 374 deaths among SGLT-2 inhibitor users at a rate of 5.8 per 100 person-years compared with 1,602 among non-users equating to 8.5 per 100 person-years.

The 25% reduction in the risk of all-cause death compared with non-use was consistent across all patient groups, including those with and without type 2 diabetes, they found.

Analysis also showed that SGLT-2 inhibitors were associated with a 23% lower risk of cardiovascular death.

But there was no reduction in a combined measure of cardiovascular death or hospitalisation for heart failure or heart failure hospitalisation alone. 

The ‘real-world’ data matches that seen in the clinical trials that had led to the recommendation of SGLT-2 inhibitors in several guidelines, including from NICE, the team concluded.

NICE recommended empagliflozin for chronic heart failure with preserved or mildly reduced ejection fraction in October 2023, following its recommendation to extend dapagliflozin use in heart failure to reduce hospitalisations in May.

‘These results support the benefits of SGLT-2 inhibitors observed in clinical trials and provide novel and important data regarding their effectiveness in real-world clinical settings and across key clinical subgroups, including patients with and without diabetes,’ the researchers from the University of Copenhagen said.

A linked editorial noted that the findings were observational but ‘provide assurance that no unexpected harm results from SGLT-2 inhibitors when they are used for treatment of heart failure outside the clinical trial setting’.

But it also stressed that SGLT-2 inhibitors are still underused, and efforts are needed to ‘tackle barriers to prescribing’ in line with best-practice guidelines.

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

NICE recommends extending dapagliflozin use in heart failure to reduce hospitalisations

22nd May 2023

NICE has recommended the extension of dapagliflozin as a treatment option for symptomatic chronic heart failure in patients with preserved or mildly reduced ejection fraction.

In final draft guidelines, the committee said it had reviewed evidence from AstraZeneca that adding dapagliflozin (Forxiga) to standard care with diuretics reduces the combined risk of dying from cardiovascular causes or hospital admission with heart failure.

The committee noted in its decision that hospitalisations for heart failure with preserved or mildly reduced ejection fraction place a substantial burden on the NHS and this is the first NICE-recommended treatment for this type of heart failure.

This follows EU approval of dapagliflozin across all ejection fractions in heart failure in February 2023.

More than 550,000 people in England have heart failure and around 50% have preserved or mildly reduced ejection fraction, of whom up to 150,000 would be eligible for treatment with dapagliflozin, NICE said.

Figures show 94,185 hospitalisations in England for heart failure in 2019/20, making it one of the leading causes of avoidable hospitalisations.

And around a quarter of people with heart failure die within the first year and over half within five years.

Positive global study for dapagliflozin

Results from the DELIVER trial considered by NICE (a global study but with no UK patients) showed dapagliflozin plus standard care reduced the composite outcome of cardiovascular death or worsening heart failure by 18% over a median follow-up of 2.3 years.

The committee said the population in the trial were about 10 years younger than would be expected in real-world the but said results were generalisable to NHS clinical practice.

An economic analysis took into account hospitalisations but also GP appointments, the final draft guidance said. Overall it found cost effectiveness to be below £20,000 per quality of life year gained – below the NICE threshold for an acceptable use of NHS resources.

Helen Knight, director of medicines evaluation at NICE, said: ‘Until now there have been no treatments available to delay or slow the progression of this type of heart failure.

‘The committee heard from patient and clinical experts who described how the lack of research and available treatments in this area led to a lack of hope and support that impacts the quality of life and mental health of people with the condition.

‘And we know that chronic heart failure also places a significant burden on the NHS through hospitalisations.’

She added: ‘Today’s draft guidance means that for the first time there is an effective treatment available on the NHS for people with this type of heart failure.

‘Not only does dapagliflozin have the potential to help them live well for longer, but it could also save the NHS money and free up space by reducing their risk of having to go to hospital for unplanned emergency treatment.’

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