DICTATE-AHF: Early dapagliflozin to manage acute HF

Dapagliflozin on top of high-dose intravenous loop diuretics just missed its primary endpoint of improving diuretic efficiency in hospitalised patients with acute heart failure (HF). Nonetheless, the results of DICTATE-AHF seems to support the early initiation of dapagliflozin to facilitate decongestion and guideline-directed medical therapy optimisation in acute HF.

“Loop diuretics plus SGLT2 inhibitors have consistently displayed to improve outcomes in patients with HF,” said Prof. Zachary Cox (Lipscomb University College of Pharmacy, TN, USA) [1]. “However, the safety and efficacy of early, in-hospital initiation of dapagliflozin have not yet been demonstrated.” Prof. Cox highlighted that there have been some concerns with the safety of administering SGLT2 inhibitors very early in hospital. “Patients may be at risk for hypoglycaemia, ketoacidosis, genitourinary infections, and worsening renal function.”

The open-label phase 3 DICTATE-AHF trial (NCT04298229) randomised 240 participants with acute HF within 24 hours after hospital admission 1:1 to dapagliflozin 10 mg daily plus structured usual care or usual care with protocolised diuretic titration only. The primary outcome was diuretic efficiency until day 5 or until hospital discharge, calculated by the cumulative weight change divided by cumulative loop diuretic dose and expressed as kg/40 mg intravenous furosemide equivalents.

The primary endpoint showed a trend of benefit for dapagliflozin with an OR of 0.65 (95% CI 0.41–1.01; P=0.06) compared with usual care; however, this did not meet statistical significance. Prof. Cox clarified that the cumulative weight change was identical for both arms, but that the median dose of cumulative loop diuretics was significantly lower in the dapagliflozin arm (560 mg vs 800 mg; P=0.006). Furthermore, 52% of the participants in the dapagliflozin arm had discontinued intravenous diuretics at day 5 compared with 33% of those in the usual care arm (P=0.006). Equal rates were observed for ‘time to discharge,’ showing that participants on dapagliflozin had a shorter time to discharge (P=0.007).

Finally, no differences were seen between both arms with regard to safety outcomes, such as worsening HF, readmission for acute decompensated HF, hypoglycaemia, genitourinary tract infections, ketoacidosis, or diabetes-related readmissions.

Although this modestly sized, open-label study did not meet its primary endpoint, it can be taken in the context of the totality of data for SGLT2 inhibitors. “The totality of the DICTATE-AHF data supports the early initiation of dapagliflozin in acute HF, to safely facilitate decongestion and optimisation of guideline-directed medical therapy,” concluded Prof. Cox.

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   1. Cox Z, et al. DICTATE-AHF: efficacy and safety of dapagliflozin in acute heart failure. Hot Line Session 6, ESC Congress 2023, 25–28 August, Amsterdam, the Netherlands.

 

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Posted on 30 October, 202330 October, 2023