Effect of In-Hospital Initiation of Dapagliflozin on Decongestion in Patients Hospitalized for Heart Failure: An Analysis of the DAPA ACT HF-TIMI 68 Trial.

BACKGROUND

Safe and effective decongestion remains an important therapeutic goal in patients hospitalized for heart failure.

OBJECTIVES

The authors evaluated the effect of dapagliflozin on multiple clinically relevant measures of congestion among patients hospitalized for heart failure.

METHODS

This was a prespecified analysis of DAPA ACT HF-TIMI 68 (Dapagliflozin Effect on Cardiovascular Events in Acute Heart Failure-Thrombolysis in Myocardial Infarction 68), a randomized, placebo-controlled trial evaluating in-hospital initiation of dapagliflozin on clinical outcomes through 2 months. The authors assessed placebo-adjusted changes from baseline in modified EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure) Composite Congestion Score (CCS), body weight, mean daily loop diuretic dose (furosemide 40 mg intravenous [IV] equivalents), and body weight adjusted for mean daily loop diuretic dose (diuretic efficiency) at 1 week, 1 month, and 2 months using linear mixed-effects models for repeated measures.

RESULTS

At randomization, 12%, 63%, and 24% had no congestion (CCS 0), mild-to-moderate congestion (CCS 1-3), and severe congestion (CCS 4-9), respectively. Compared with placebo, dapagliflozin improved all decongestion-related endpoints by 1 week, including CCS (least squares mean difference [LSMD]: -0.18; 95% CI: -0.33 to -0.04; P = 0.011), body weight (LSMD: -0.60 kg; 95% CI: -0.95 to -0.26; P < 0.001), mean daily loop diuretic dose (LSMD: -0.12 furosemide 40-mg IV equivalents; 95% CI: -0.22 to -0.02; P = 0.014), and diuretic efficiency (LSMD: -0.93 kg/furosemide 40 mg IV equivalents; 95% CI: -1.61 to -0.25; P = 0.008). These improvements were sustained through 2 months, with progressive increases in diuretic efficiency through 2 months (LSMD: -1.99 kg/furosemide 40 mg IV equivalents; 95% CI: -3.19 to -0.78; P < 0.001).

CONCLUSIONS

In-hospital initiation of dapagliflozin led to modest but significant improvements across multiple measures of congestion within 1 week that were sustained through 2 months. Diuretic efficiency progressively improved through 2 months. (Dapagliflozin Effect on Cardiovascular Events in Acute Heart Failure-Thrombolysis in Myocardial Infarction 68 [DAPA ACT HF-TIMI 68]; NCT04363697).