Update on clinical heart failure trials

Abstract Heart failure (HF) remains a major global health burden, with rising prevalence and significant morbidity and mortality despite advances in diagnosis and management. Over the past years, the therapeutic landscape of HF has evolved substantially, driven by a growing number of pivotal clinical trials addressing not only heart failure with reduced ejection fraction (HFrEF), but also heart failure with mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF). The following review provides a comprehensive update on key clinical trials published or presented in the recent past such as DIGIT-HF, VICTORIA and VICTOR, STRONG-HF, SUMMIT or STEP-HFpEF trials, highlighting novel pharmacological therapies, patient phenotyping, and treatment of co-morbidities. Special attention is given to trials with practice changing implications and those shaping future guidelines. Graphical Abstract Central illustration: ACEi angiotensin-converting enzyme inhibitor, ARB angiotensin receptor blocker, ARNI angiotensin receptor–neprilysin inhibitor, CV cardiovascular, GDMT guideline-directed medical therapy, GLP-1 glucagon-like peptide-1, HFmrEF heart failure with mildly reduced ejection fraction, HFpEF heart failure with preserved ejection fraction, HFrEF heart failure with reduced ejection fraction, HHF hospitalization for heart failure, LVEF left ventricular ejection fraction, MRA mineralocorticoid receptor antagonist, SGLT2i sodium-glucose cotransporter 2 inhibitor, uNa⁺ urinary sodium.