Andre M Small, Siddharth M Patel, Colleen Thomas, Michael G Palazzolo, Jan Bělohlávek, Akshay S Desai, Jarosław Drożdż, Silvio E Inzucchi, John J V McMurray, Béla Merkely, Eileen O'Meara, Subodh Verma, Stephen D Wiviott, Marc S Sabatine, David D Berg
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).
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).