Impact of dapagliflozin treatment on renal function and diuretics use in acute heart failure: a pilot study

Abstract

ObjectiveTo determine the impact of sodium-dependent glucose type 2 cotransporter inhibitors on the renal function in acute heart failure.MethodsIn a single-centre, controlled, randomised study, patients were prescribed dapagliflozin in addition to standard therapy, or were in receipt of standard therapy. The prespecified outcome was renal function deterioration; the secondary outcomes were the development of resistance to diuretics, weight loss, death during hospitalisation and the rehospitalisation or death for any reason within 30 days following discharge.Results102 patients were included (73.4±11.7 years, 57.8% men). The average left ventricular ejection fraction was 44.9%±14.7%, the average N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was 4706 (1757; 11 244) pg/mL, the average estimated glomerular filtration rate (eGFR) was 51.6±19.5 mL/min. eGFR decreased 48 hours after randomisation in the dapagliflozin group (−4.2 (−11.03; 2.28) mL/min vs 0.3 (−6; 6) mL/min; p=0.04) but did not differ between the groups on discharge (54.71±19.18 mL/min and 58.92±24.65 mL/min; p=0.36). The incidence of worsening renal function did not differ (34.4% vs 15.2%; p=0.07). In the dapagliflozin group, there was less tendency to increase the dose of loop diuretics (14% vs 30%; p=0.048), lower average doses of loop diuretics (78.46±38.95 mg/day vs 102.82±31.26 mg/day; p=0.001) and more significant weight loss (4100 (2950; 5750) g vs 3000 (1380; 4650) g; p=0.02). In-hospital mortality was 7.8% (4(8%) in the dapagliflozin and 4 (7.7%) in the control group (p=0.95). The number of deaths within 30 days following discharge in the dapagliflozin group and in the control group was 9 (19%) and 12 (25%), p=0.55; the number of rehospitalisations was 14 (29%) and 17 (35%), respectively (p=0.51).ConclusionThe use of dapagliflozin was associated with a more pronounced weight loss and less need to increase diuretic therapy without significant deterioration of the renal function. Dapagliflozin did not improve the in-hospital and 30-day prognosis after discharge.Trial registration numberN04778787.

Cardiovascular and renal effects of SGLT2 inhibitor initiation in acute heart failure: a meta-analysis of randomized controlled trials

“…Due to high heterogeneity, we performed a leave-one-out sensitivity analysis by iteratively removing one study at a time to ensure the results were not dependent on a single study. The removal of each study from the pooled analysis did not affect the WRF endpoint, except for the study from Charaya et al [ 22 ]. The withdrawal of this study reduced the frequency of WRF in the SGLT2i group compared with the control group and eliminated the heterogeneity in the endpoint (OR 0.64; 95% CI 0.43–0.95; p = 0.029; I 2 = 0%; Fig.…”

“…Fifth, the outcomes of mean daily urinary output and mean daily dose of loop diuretics were based on small samples, as these outcomes were not reported in all studies, with broad confidence intervals and high heterogeneity. And, finally, the endpoint of WRF had elevated heterogeneity, identified as originating from Charaya et al [ 22 ]. This study found a non-statistically significant increase in WRF with SGLT2i relative to no SGLT2i therapy.…”

Earlier is Better. New Options for Acute Heart Failure: When, Who, How Much?

“…Transient GFR reduction is considered a sign of successful decongestion and it is not associated with loss of functional nephrons. [22] A retrospective study from the EMPA REG OUTCOMES trial database divided the patients into three groups depending on the GFR decrease during therapy with empagliflozin: >10%, 0-10%, and no change. For those patients exposed to empagliflozin 10 -25 mg, there were 41% non-dippers, 31% with intermediary response, and 28% dippers.…”

The Therapeutic Role of SGLT-2 Inhibitors in Acute Heart Failure: From Pathophysiologic Mechanisms to Clinical Evidence with Pooled Analysis of Relevant Studies across Safety and Efficacy Endpoints of Interest

“…Our search retrieved six RCTs [59][60][61][62][63][64] and two observational studies [65,66], in total. Of note, one trial, the Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post-Worsening Heart Failure (SOLOIST-WHF) trial [64] enrolled subjects with T2DM and a recent hospitalization for acute decompensation of HF, therefore, it did not assess the safety and efficacy of SGLT-2 inhibitors in the "strict" setting of acute HF.…”