Improving outcomes for patients with HFpEF and obesity: The STEP-HFpEF trial
Both obesity and heart failure with preserved ejection fraction (HFpEF) are rising health problems around the world and appear interlinked – obesity may lead to or accelerate HFpEF, with a distinct phenotype and worsened outlook in these patients. The huge symptom burden in HFpEF means patients consider quality of life (QoL) improvement as important a treatment outcome as hospitalisation and even death. Therefore, the FDA has designated symptom/functional capacity improvement a treatment target in HF that can alone lead to approval of new therapies.
However, there is currently no treatment approved for improving the huge symptom burden in people with HFpEF and obesity.
Aiming to address this need, Kosiborod and colleagues share outcomes from the STEP-HFpEF trial in adults with HFpEF and obesity (body mass index ≥30). The authors used the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) and weight change as the primary endpoints in patients receiving 2.4 mg once-weekly subcutaneous semaglutide vs placebo (with standard of care), with KCCQ assessing the extent of symptoms and overall function/QoL.
At 52 weeks, semaglutide vs placebo significantly improved KCCQ-CSS and reduced weight (P=0.001). The slope of these improvements leads authors to conclude that semaglutide independently targets obesity and HFpEF physiology – likely via shared anti-inflammatory and haemodynamic mechanisms – and leads to a cumulative improvement in outcomes for both.
Semaglutide treatment vs placebo also improved secondary endpoints: it increased the 6-minute walk distance and reduced a composite score that reflected HF-related incidents (i.e. death, HF events and HF-related hospitalisation/urgent visits).
Semaglutide similarly reduced the levels of N-terminal prohormone of brain natriuretic peptide (NTproBNP), a blood marker that rises in HFpEF but decreases in obesity, again indicating improvement of haemodynamic pathways common to both obesity and HF. The HFpEF improvement was also reflected in the sharp decrease in adjusted HF events and cardiovascular adverse events in the semaglutide group vs placebo, further evidence of semaglutide improving physiological mechanisms behind both disorders.
The effect of semaglutide beyond 52 weeks and in a more ethnically diverse population needs investigating.
The authors conclude that semaglutide can be a good candidate for effective symptom and functional improvement – a treatment target very important to patients suffering from the double whammy of HFpEF and obesity.
The full article can be read here.
