Contemporary medical therapy for heart failure with mildly reduced or preserved ejection fraction

Abstract

Treatment for heart failure with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) has evolved significantly in recent years. This period of therapeutic progress follows a span of over two decades during which randomized controlled trials (RCTs) of neurohormonal blockade and other therapies failed to definitively demonstrate clinical benefits. As such, traditionally, management guidelines for HFmrEF and HFpEF were limited to recommendations focused on optimization of volume status with diuretics, management of comorbidities, and consideration of certain medications such as angiotensin receptor-neprilysin inhibitor (ARNi) or steroidal mineralocorticoid receptor antagonists (MRA) to subsets of patients. After definitive results from multiple RCTs, sodium-glucose cotransporter 2 inhibitors (SGLT2i) are currently a main pillar in treating HFmrEF and HFpEF in European and American guidelines. However, other therapies, including non-steroidal mineralocorticoid receptor antagonists (nsMRA) and glucagon-like peptide-1 receptor agonists (GLP-1 RA), are proving to be additional effective treatments for HFmrEF and HFpEF and preventing the progression of cardiovascular-kidney-metabolic (CKM) syndrome. There is now increasing justification for combining multiple proven treatments for HFmrEF and HFpEF to maximize potential benefits. Treatment for different types of heart failure has improved significantly in recent years. For many years, there were few treatments that clearly helped people with heart failure whose heart still pumps normally or nearly normally. Care mainly focused on treating symptoms, helping the body remove excess fluid, and managing related health conditions such as high blood pressure, diabetes, and obesity. Today, research has expanded the available treatment options. One important group of medicines helps the body remove excess sugar and salt through the urine, which also reduces excess fluid and lowers the strain on the heart. Newer studies have shown that medicines that block the effects of a hormone called mineralocorticoid can improve outcomes while causing fewer side effects than older steroid-based treatments. For people who also have obesity, another newer group of medicines that acts on natural gut hormones has been shown to improve symptoms, physical activity, and quality of life. Overall, using a combination of these newer treatments may help people with heart failure whose heart still pumps normally or nearly normally feel better, improve their quality of life, and achieve better long-term health outcomes.