Heart failure is the most common cause of cardiovascular-related hospitalizations worldwide, with admission rates continuing to rise. It currently affects around 6.7 million Americans over the age of 20, a number projected to reach 8.5 million by 2030.1 Acute decompensated heart failure is a critical clinical condition marked by fluid overload that could be associated with impaired renal function and resistance to diuretic therapy.2 Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown significant reduction in the mortality and hospitalization due to heart failure in patients with stable chronic heart failure, regardless of their left ventricular ejection fraction.3,4

Despite the clear benefit of SGLT2 inhibitors in chronic heart failure, their use during episodes of acute decompensation remains under investigation. Evidence from outpatient heart failure trials indicates that the cardioprotective benefits of SGLT2 inhibitors manifest early, supporting timely initiation of therapy.5,6 However, patients hospitalized with heart failure may be more vulnerable to treatment-related complications due to hemodynamic or rhythm instability, and the frequent initiation or intensification of other heart failure therapies.7

Recently, the DAPA ACT HF-TIMI 68 (Dapagliflozin Effect on Cardiovascular Events in Acute Heart Failure – Thrombolysis in Myocardial Infarction 68) trial demonstrated that early initiation of SGLT2 inhibitors did not significantly reduce the risk of cardiovascular death or worsening heart failure.8 In contrast, the SOLOIST-WHF (Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure) trial found that starting SGLT2 inhibitors before or shortly after hospital discharge significantly lowered the composite of cardiovascular deaths, hospitalizations, and urgent heart failure visits compared with placebo.9,10 In light of these conflicting findings, we conducted a systematic synthesis of the available clinical trial evidence to assess the safety and efficacy of early initiation of SGLT2 inhibitors in patients hospitalized with decompensated heart failure.