Abstract: Loop diuretics are the cornerstone of worsening heart failure (HF) therapy. However, an important challenge faced by HF patients is that despite taking a large amount of loop diuretics, they still exhibit fluid overload. There is no enough evidence of diuretics reducing the mortality of HF patients. Brain natriuretic peptides enhancer and sodium-glucose transporter 2 inhibitors with unique natriuretic effect, can improve neurohormonal activation without increasing renal injury and electrolyte disturbance. Combined with loop diuretics, they can increase urine volume in the short term and improve the prognosis in the long term, providing a new paradigm for the management of worsening HF.