Targeting Superoxide to Prevent Diuretic Resistance and Reduce Heart Failure Mortality

Diuretic resistance is a servomechanism involving superoxide that results in the need for escalating doses of diuretics in the treatment of heart failure. Without intervention, this typically is associated with increased heart failure mortality. Recent heart failure studies involving the use of SGLT2 inhibitors and GLP-1 agonists have shown reductions in the need for loop diuretics along with reductions in hospitalizations for heart failure and cardiovascular mortality. Multiple mechanisms have been suggested to explain the benefits of both these and related drugs, but this article is the first to propose superoxide-induced diuretic resistance as a therapeutic target for improving outcomes and reducing mortality in the treatment of heart failure.