Are SGLT-2 Inhibitors the Future of Heart Failure Treatment? The EMPEROR-Preserved and EMPEROR-Reduced Trials

Heart failure is frequently associated with diabetes, and therapies which reduce mortality in people with heart failure and reduced ejection fraction (HFrEF) are often limited to drugs which modulate the renin–angiotensin–aldosterone system or heart rate control and occasionally to device therapy. Treatment is even more challenging in people with heart failure and preserved ejection fraction (HFpEF), with currently no approved therapy demonstrating a mortality-improving effect, limiting treatment to diuretics for the alleviation of the symptoms of fluid overload and risk factor management. Previous cardiovascular outcome trials for sodium-glucose co-transporter-2 (SGLT-2) inhibitors have demonstrated significant favourable outcomes for cardiovascular disease, heart failure hospitalisation and all-cause mortality. The aim of the nearly completed EMPEROR-preserved and EMPEROR-reduced trials is to determine the impact of empagliflozin on cardiovascular and heart failure outcomes in people with HFpEF or HFrEF with or without diabetes. The trials will add substantially to our understanding of SGLT-2 inhibitors in the treatment of HFrEF and may have major implications for the treatment of people with HFpEF. The study will also be powered to address the impact of empagliflozin on changes in renal function in people with and without diabetes and incident diabetes in the participants without diabetes at baseline. In this article we discuss the rationale for using SGLT-2 inhibitors in people with heart failure and explore the potential findings and importance of the ongoing EMPEROR-preserved and EMPEROR-reduced trials.