STEP-HFpEF trial – caveats and implications
STEP-HFpEF was a randomised, controlled trial designed to find out whether semaglutide for 52 weeks could improve heart failure symptoms and physical function in obese, non-diabetic patients with heart failure with preserved ejection fraction (HFpEF). In this series of short videos, Vicky Ruszala, Specialist Cardiology Pharmacist, North Bristol NHS Trust describes the trial findings and the implications.
Could semaglutide help obese patients with heart failure?
HFpEF – commonly known as ‘hef-pef’ – refers to heart failure with preserved ejection fraction, a condition for which no treatment has hitherto been available. Current thinking suggests that obesity may be a causative factor in HFpEF rather than a co-morbidity. “In the U.S. about 80 percent of patients with HFpEF also have obesity”, says Ms Ruszala Therefore, STEP-HFpEF was designed to investigate whether treating obesity in such patients had an impact on their heart failure.
The trial had dual primary endpoints comprising quality of life (using the Kansas City Cardiomyopathy Questionnaire (KCCQ) score) and weight loss.
How semaglutide impacts HFpEF
“The findings [of the STEP-HFpEF trial] were very definitive”, says Ms Ruszala. There was an eight-point difference in the KCCQ score. (A minimum four-point difference is clinically significant). “The patients who were on semaglutide felt much better, had far, far [fewer] symptoms and were able to do more in their daily life with increased exercise capacity”, she explains. In addition, there was an 11 percent greater body weight loss in the semaglutide group compared with the placebo group. Both endpoints were statistically significant. Furthermore, the hierarchical secondary endpoints were all met.
Previous trials of weight loss combined with exercise have shown benefits in quality of life but not to the same extent as those seen with semaglutide. Moreover, “the weight loss itself wasn’t significant enough in many of the previous trials, so there was something extra seen in [this trial] that wasn’t previously”, says Ms Ruszala.
Semaglutide for prevention or cure of HFpEF?
The results of the STEP-HFpEF trial point towards routine use of GLP-1 agonists in heart failure but this has to be balanced against conflicting guidelines and cost pressures in the NHS. “We know there’s benefit [from] GLP-1s in kidney disease, we know there’s benefit [from] GLP-1s in type 2 diabetes; we now know there’s benefit in heart failure as well”, says Ms Ruszala.
The new ESC guidance (European Society of Cardiology guidance) for heart failure or heart disease and diabetes that was launched in August , already says anyone who has heart failure and type 2 diabetes should be given dual therapy with an SGLT-2 (sodium-glucose co-transporter-2 inhibitor) and a GLP-1 agonist. However, this is not yet in the UK heart failure guideline and this presents UK cardiologists with a dilemma.
Currently the UK approach to the use of semaglutide in heart failure is different from the approach elsewhere in Europe. “I think it goes back to the prevention versus cure [question]. At the moment our guidance is set up as cure …… [but] this kind of medicine is preventative. If you give semaglutide or another GLP-1 to somebody early in their diabetes pathway, early in their HFpEF pathway, the likelihood is that they will be much better, fitter and [generally well] for much longer” says Ms Ruszala.
However, semaglutide is not available in the UK currently and it’s not likely to be available in the UK until 2024. Much can be achieved with the existing treatment protocols and there should be a strong focus on optimising treatment with the available medicines, she suggests.
About Vicky Ruszala
As a specialist cardiology pharmacist, a large part of Vicky Ruszala’s work involves optimising medications for heart failure. She works on the specialist cardiology ward and also has two heart failure clinics each week. She is an independent prescriber and has her own patient caseload.