Impact of empagliflozin on decongestion in acute heart failure: the EMPULSE trial. (18th October 2022)

• Record Type: Journal Article
• Authors: Biegus, Jan; Voors, Adriaan A; Collins, Sean P; Kosiborod, Mikhail N; Teerlink, John R; Angermann, Christiane E; Tromp, Jasper; Ferreira, Joao Pedro; Nassif, Michael E; Psotka, Mitchell A; Brueckmann, Martina; Salsali, Afshin; Blatchford, Jonathan P; Ponikowski, Piotr
• Is Part Of: European heart journal. Volume 44:Number 1(2023)
• Page Start: 41
• Page End: 50
• Publication Date: 2022-10-18
• Subjects: SGLT-2 inhibitor -- Decongestion -- Acute heart failure -- Empagliflozin; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehac530
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Aims: Effective and safe decongestion remains a major goal for optimal management of patients with acute heart failure (AHF). The effects of the sodium–glucose cotransporter 2 inhibitor empagliflozin on decongestion-related endpoints in the EMPULSE trial (NCT0415775) were evaluated. Methods and results: A total of 530 patients hospitalized for AHF were randomized 1:1 to either empagliflozin 10 mg once daily or placebo for 90 days. The outcomes investigated were: weight loss (WL), WL adjusted for mean daily loop diuretic dose (WL-adjusted), area under the curve of change from baseline in N-terminal pro-B-type natriuretic peptide levels, hemoconcentration, and clinical congestion score after 15, 30, and 90 days of treatment. Compared with placebo, patients treated with empagliflozin demonstrated significantly greater reductions in all studied markers of decongestion at all time-points, adjusted mean differences (95% confidence interval) at Days 15, 30, and 90 were: for WL −1.97 (−2.86, −1.08), −1.74 (−2.73, −0.74); −1.53 (−2.75, −0.31) kg; for WL-adjusted: −2.31 (−3.77, −0.85), −2.79 (−5.03, −0.54), −3.18 (−6.08, −0.28) kg/40 mg furosemide i.v. or equivalent; respectively (all P < 0.05). Greater WL at Day 15 (i.e. above the median WL in the entire population) was associated with significantly higher probability for clinical benefit at Day 90 (hierarchical composite of all-cause death, heart failure events, and a 5-point or greater difference in Kansas City Cardiomyopathy Questionnaire total symptom score change from baseline to 90 days) with the win ratio of 1.75 (95% confidence interval 1.37, 2.23; P < 0.0001). Conclusion: Initiation of empagliflozin in patients hospitalized for AHF resulted in an early, effective and sustained decongestion which was associated with clinical benefit at Day 90. Structured Graphical Abstract: Structured Graphical Abstract Empagliflozin in acute heart failure: the EMPULSE Trial. CI, confidence interval. Data shown for the treatment effect graphs are adjusted mean change from baseline, with error bars representing standard error. *The units of weight changes per mean daily loop diuretic dose are presented in kg/40 mg of intravenous furosemide (or 80 mg of oral furosemide) or equivalent. The equivalent to 40 mg of furosemide was defined as 20 mg of torasemide or 1 mg of bumetanide. † Measured as changes in haematocrit (%). ‡ Calculated as a sum of the points allocated for dyspnoea, orthopnoea and fatigue. For each variable, a 0- to 3-point scale has been used, where points were allocated for: absence (0 points), seldom (1 point), frequent (2 points), and continuous (3 points) based on the frequency of the clinical sign. § The hierarchy and the components of the primary outcome measured by the win ratio: 1. Time to all-cause death; 2. Number of heart failure (HF) events (including hospitalizations for HFs, urgent HF visits and unplanned outpatient visits); 3. Time to first HF event; 4. ≥5 point difference in change from baseline in KCCQ total symptom score (KCCQ-TSS) after 90 days of treatment.