DICTATE-AHF and PUSH-AHF Shed New Light on Treating Acute HF

Two separate Hotline trials presented at ESC Congress 2023 – DICTATE-AHF and PUSH-AHF – shed light on treatments for patients with acute heart failure (HF).

In DICTATE-AHF, researchers assessed the efficacy and safety of the SGLT2 inhibitor, dapagliflozin (10 mg once daily), initiated within 24 hours of hospital admission in adult patients with hypervolaemic acute decompensated HF (ADHF).

Participants with type 2 diabetes and an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73m2, and who were admitted to hospital with ADHF and undergoing current or planned treatment with intravenous (IV) loop diuretics, were initially included in the study, with an amendment added in September 2021 to address new safety data that allowed enrollment of patients with or without type 2 diabetes and an eGFR of at least 25 mL/min/1.73m2.

All told, 240 patients (median age 65 years; 39% women) were randomized to either daily dapagliflozin or structured usual care for five days or hospital discharge. Natriuretic peptide concentration, standing weight, and congestion were assessed at baseline.

Overall results found dapagliflozin did not result in a statistically significant improvement in diuretic efficiency relative to structured usual care. After adjustment for baseline, the primary outcome of diuretic efficiency from enrollment to day five or discharge was 0.65 for dapagliflozin vs. structured care. The secondary endpoints of in-hospital worsening HF and 30-day readmission for HF or diabetes-related reasons did not differ between the two groups.

In other findings, dapagliflozin significantly increased both 24-hour natriuresis (p=0.025) and 24-hour urine output (p=0.005) and decreased both time to completing IV diuretic therapy (p=0.006) and time to hospital discharge (p=0.007), according to researchers. Early dapagliflozin initiation was also observed to be safe across all diabetic and cardiorenal in-hospital outcomes, with no differences between groups in the change in eGFR from baseline to end-of-study, incidence of adverse events, inpatient mortality, symptomatic hypotension, total or serious hypoglycemia events, genitourinary infections, or severe hypokalemia.

"Although our study did not show statistical significance for its primary endpoint, the totality of data from this trial supports the early initiation of dapagliflozin in ADHF to facilitate decongestion while rapidly and safely optimizing GDMT," said Zachary Cox, PharmD, of Lipscomb University College of Pharmacy, Nashville, TN. "Our findings of safety across inpatient diabetes, cardiovascular and renal outcomes should encourage in-hospital use, which can translate to improved chronic SGLT2 inhibitor prescription, adherence, and long-term benefits."

In PUSH-AHF, researchers found that a pragmatic natriuresis-guided diuretic approach to managing patients with acute HF significantly increased 24-hour natriuresis without impacting all-cause mortality or hospitalization for HF.

A total of 310 patients in the Netherlands (median age 74 years; 45% women) presenting with acute HF and requiring treatment with intravenous loop diuretics were enrolled in the study and randomized to either natriuresis guided diuretic therapy or standard of care using electronic health records. In the natriuresis-guided group, spot urinary sodium was determined at two, six, 12, 18, 24 and 36 hours after starting intravenous loop diuretics. Diuretic therapy was consequently intensified using a prespecified stepwise approach if needed.

Results found natriuresis during the first 24 hours was significantly higher in the natriuresis-guided vs. standard of care group. There was no significant difference in the combined endpoint of time to all-cause mortality or first HF rehospitalization at 180 days between the two groups (31% in both). In other findings, natriuresis-guided therapy resulted in increased 48-hour natriuresis, 24-hour diuresis and 48-hour diuresis. There were no significant differences between the two group in terms of length of hospital stay, safety profile and prespecified renal safety endpoints or worsening renal function.

"The results confirm the hypothesis that early, repeated assessment of urinary sodium and subsequent adjustments to diuretic treatment led to better response," said Jozine ter Maaten, MD, of the University Medical Centre Groningen. "Although 180-day clinical outcome was not affected in this relatively small sample size, the strategy was safe and did not result in significant renal or electrolyte perturbations compared with standard of care. Clinicians should consider natriuresis-guided diuretic therapy as a first step to a personalized treatment approach in patients with acute HF to improve decongestion."

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Acute Heart Failure

Keywords: ESC Congress, ESC23, ACC International, Diuretics, Heart Failure, Sodium-Glucose Transporter 2, Diabetes Mellitus

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