Dapagliflozin in Patients Hospitalized for Heart Failure: Primary Results of the DAPA ACT HF-TIMI 68 Randomized Clinical Trial and Meta-Analysis of Sodium-Glucose Cotransporter-2 Inhibitors in Patients Hospitalized for Heart Failure

Abstract

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce the risk of cardiovascular death or worsening heart failure (HF) in outpatients with HF. Data are limited regarding initiation in patients hospitalized for HF.

Methods: We conducted a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of in-hospital initiation of dapagliflozin (10 mg daily) in patients hospitalized for HF. The primary efficacy outcome was a composite of time to cardiovascular death or worsening HF through two months. Key safety outcomes included symptomatic hypotension and worsening kidney function. A prespecified meta-analysis was performed of randomized trials evaluating initiation of SGLT2i in hospitalized HF patients.

Results: Of 2401 patients (median age 69 [Q1-Q3, 58-77] years, 815 [33.9%] women, 448 [18.7%] Black race, 1717 [71.5%] LVEF ≤40%, 1074 [44.7%] newly diagnosed), randomized between 09/2020 and 03/2025, 1218 were assigned to dapagliflozin and 1183 to placebo. The primary outcome occurred in 133 patients (10.9%) in the dapagliflozin group and 150 (12.7%) in the placebo group (hazard ratio [HR], 0.86; 95% CI 0.68-1.08; p=0.20). A worsening HF event occurred in 115 (9.4%) and 122 (10.3%) patients in the dapagliflozin and placebo groups, respectively (HR, 0.91; 95% CI, 0.71-1.18). Cardiovascular death occurred in 30 (2.5%) and 37 (3.1%) patients (HR, 0.78; 95% CI, 0.48-1.27), and death from any cause occurred in 36 (3.0%) and 53 (4.5%) patients in the dapagliflozin and placebo groups, respectively (HR, 0.66; 95% CI, 0.43-1.00). The rates of symptomatic hypotension were 3.6% and 2.2%, and the rates of worsening kidney function were 5.9% and 4.7% with dapagliflozin and placebo, respectively. In a meta-analysis of patients hospitalized for HF, SGLT2i reduced the early risk of cardiovascular death or worsening HF (HR, 0.71; 95% CI, 0.54-0.93; p=0.012) and of all-cause death (HR, 0.57; 95% CI, 0.41-0.80; p=0.001).

Conclusions: In-hospital initiation of dapagliflozin did not significantly reduce the risk of cardiovascular death or worsening HF through two months in hospitalized HF patients. However, the totality of randomized clinical trial data suggests that in-hospital initiation of SGLT2i may reduce the early risk of cardiovascular death or worsening HF and of all-cause mortality.