Diuretic Potentiation Strategies in Acute Heart Failure

Several trials have evaluated diuretic-based strategies to improve symptoms and outcomes in patients with acute heart failure (AHF). The authors sought to summarize the effect of different combination strategies on symptoms, physical signs, physiological variables, and outcomes in patients with AHF. Twelve trials were identified that assessed the addition of thiazide diuretics, sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, vasopressin receptor antagonists, carbonic anhydrase inhibitors, or loop diuretic intensification to conventional therapy for AHF. The trials evaluated short-term markers of congestion and symptoms, and none were powered for clinical outcomes. Short-term responses (such as relief from dyspnea, physical signs of congestion, and weight change) varied greatly across studies; all diuretic strategies were accompanied by short-term increases in serum creatinine and did not demonstrate benefits on mortality or recurrent heart failure events. The available evidence suggests that intensification of loop diuretic agents produces relief of physical signs of decongestion, but the importance of different strategies for short-term decongestion strategy for health status and long-term outcomes has not been established. (JACC Heart Fail. 2025;13:14-27) (c) 2025 by the American College of Cardiology Foundation.