In this study, 2,401 patients with decompensated heart failure were randomized while still hospitalized to receive either dapagliflozin 10 mg or placebo. The primary composite endpoint was cardiovascular death or a first heart failure event within 60 days. The study aimed to determine whether early treatment with the SGLT2 inhibitor dapagliflozin improves these outcomes.
Participants had a mean age of 69 years and 34% were female. Up to 70% had a left ventricular ejection fraction ≤40%, and 45% had newly diagnosed heart failure. The primary endpoint was not significantly reduced compared to placebo (HR 0.86; 95% CI [0.68; 1.08]; p=0.20). Similarly, heart failure events (rehospitalization or urgent presentation due to heart failure) were not significantly lower in the dapagliflozin arm (HR 0.91; 95% CI [0.71; 1.18]). CV death (HR 0.78; 95% CI [0.48; 1.27]) and all-cause death (HR 0.66; 95% CI [0.43; 1.00]) tended to be lower with dapagliflozin, but the difference was not statistically significant.
Serious adverse events were uncommon: symptomatic hypotension occurred in i3.6% vs 2.2% and worsening renal function in 5.9% vs 4.7% (dapagliflozin vs. placebo). No cases of ketoacidosis were reported.
A prespecified meta-analysis published alongside the primary results, which also included EMPULSE and SOLOIST, showed that early SGLT2 inhibition in patients hospitalized for heart failure reduced both CV deaths and heart failure events (HR 0.71; 95% CI [0.54; 0.93]; p=0.012) as well as all-cause mortality (HR 0.57; 95% CI [0.41; 0.80]; p=0.001).
Together with the meta-analysis, DAPA ACT HF-TIMI 68 confirms that early administration of SGLT2 inhibitors (especially dapagliflozin and empagliflozin) is safe in patients with heart failure and reduces early cardiovascular deaths and heart failure events. This is clinically relevant because early SGLT2 inhibition not only supports faster decongestion but also improves the long-term prognosis of heart failure patients, regardless of left ventricular ejection fraction, as part of guideline-based heart failure therapy.
