According to research presented at this year’s European Society of Cardiology (ESC) Congress, early initiation of dapagliflozin does not significantly improve diuretic efficiency in hospitalised patients with acute decompensated heart failure (ADHF) compared to standard care.

However, the research found that early initiation of dapagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, can be safely administered once a patient with ADHF has been admitted to hospital to promptly optimise guideline-directed medical therapy (GDMT). This results in improved decongestion and being discharged from hospital earlier.

Dapagliflozin is typically prescribed to treat type 2 diabetes but can also be prescribed for people with heart failure and chronic kidney disease (CKD).

Dapagliflozin reduces how much work the heart needs to do to pump blood round the body and therefore reduces the likelihood of the heart weakening and improves heart failure symptoms like tiredness.

When a patient is hospitalised with ADHF, the two main goals are complete decongestion and optimisation of GDMT. Past studies investigating diuretic combinations have resulted in improved decongestion but, overall, did not optimise GDMT or post-discharge outcomes.

The DICTATE-AHF trial set out to examine the efficacy and safety of initiating dapagliflozin within the first day of hospital presentation to optimise GDMT and decongestion in patients with hypervolemic ADHF.

The trial involved 240 patients living with type 2 diabetes with an average age of 65, 39% of which were women. The participants had “an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73m2 admitted to hospital with ADHF and current or planned treatment with intravenous (IV) loop diuretics”.

The ESC said: “In September 2021, the protocol was amended to allow enrolment of patients with or without type 2 diabetes and to decrease the eGFR inclusion criterion to 25 mL/min/1.73m2 due to new safety data in these groups. The main exclusion criteria were type 1 diabetes, systolic blood pressure less than 90 mmHg, serum glucose less than 80 mg/dL, use of IV inotropic therapy, and history of diabetic ketoacidosis.”

During their first day in hospital, patients were randomly assigned either oral dapagliflozin 10 mg once daily or structured usual care until they were discharged or on their fifth day in hospital. On day one, their natriuretic peptide concentration, standing weight and congestion was measured for baseline.

For both groups, the researchers used a consistent protocol for IV loop diuretic dosing and titration every 12-24 hours, aiming for a daily urine output of three to five litres. The ESC added: “Loop diuretic doses were titrated to a dose of at least 960 mg/day of IV furosemide equivalents before a thiazide diuretic was added.”

After the first IV loop diuretic dose, but before receiving any dapagliflozin, a urine sample was collected to provide a baseline measurement for diuretic-induced urine sodium, potassium and creatinine.

Urine samples were then collected again on day 2. On day 5 or upon discharged, natriuretic peptide concentration, final standing weight and congestion assessments were performed again. 30 days after discharge, follow-ups took place to evaluate post-discharge outcomes.

The European Society of Cardiology stated: “The primary outcome was diuretic efficiency (diuretic response) expressed as the cumulative change in weight per cumulative loop diuretic dose (IV and oral) from enrolment to day 5 or discharge, if sooner. The primary outcome was compared across treatment assignment using a proportional odds regression model adjusting for baseline weight.

“After adjusting for baseline weight, the odds ratio (OR) for diuretic efficiency with dapagliflozin versus structured care was 0.65, 95% confidence interval (CI) 0.41 to 1.01, p=0.06. In the unadjusted analysis, the OR was 0.64, 95% CI 0.41 to 1.00, p=0.05.”

It added: “The secondary endpoints of in-hospital worsening heart failure and 30-day readmission for heart failure or diabetes-related reasons did not differ between early dapagliflozin initiation compared to usual care.”

The outcome of the trial highlighted that dapagliflozin considerably increases natriuresis and urine output whilst decreasing the time it takes to complete IV diuretic therapy and be discharged from hospital.

The ESC summarised: “Early dapagliflozin initiation was safe across all diabetic and cardiorenal in-hospital outcomes, with no differences between treatment groups in the change in eGFR from baseline to end-of-study, incidence of adverse events, inpatient mortality, symptomatic hypotension, total or serious hypoglycaemia events, genitourinary infections, or severe hypokalaemia.”

Study author, Professor Zachary Cox of Lipscomb University College of Pharmacy in Nashville, said: “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 optimising GDMT.

“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.”

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