Comparison of 2 diuretic strategies for HF with diuretic resistance

DAPA-RESIST clinical trial - Dapagliflozin versus metolazone in heart failure with diuretic resistance

News - May 25, 2023

Presented at the ESC Heart Failure 2023 by: Ross Campbell, PhD - Glasgow, UK

Introduction and methods

In patients with HF, diuretic resistance is associated with worse clinical outcomes. A commonly used therapeutic strategy for this condition combines 2 diuretics: a thiazide (or thiazide-like) and loop diuretic. Treatment with SGLT2 inhibitors, which act on the proximal convoluted tubule, results in increased diuresis in acute HF and renal protection and is associated with better outcomes in both HF and kidney failure. Based on these benefits, SGLT2 inhibitors may also be useful in patients with HF and diuretic resistance.

The DAPA-RESIST (DAPAgliflozin Versus Thiazide Diuretic in Patients With Heart Failure and Diuretic RESISTance) trial was a pragmatic, multicenter, open-label RCT conducted in the UK. In this trial, 61 patients who were admitted for HF and showed diuretic resistance despite treatment with an intravenous (IV) loop diuretic were randomized to 1 of the following 2 dual diuretic strategies: either the SGLT2 inhibitor dapagliflozin 10 mg or the thiazide-like diuretic metolazone 5–10 mg, both for up to 3 consecutive days and in addition to usual care with IV furosemide. Diuretic resistance was defined as weight loss<1 kg, or <1 l negative fluid balance in preceding 24 hours.

The primary endpoint was the mean change in body weight (in kg) between baseline and 96 hours. Secondary endpoints were change in congestion as assessed with lung ultrasound; loop diuretic efficiency (change in body weight in kg per 40-mg dose of furosemide); and modified ADVOR (Acetazolamide in Decompensated Heart Failure with Volume Overload) congestion score. Safety outcomes included changes in kidney function and serum sodium and potassium levels between baseline and 96 hours.

Main results

  • Both diuretic strategies resulted in weight loss. Although the mean change in body weight at 48–96 hours was numerically lower in patients treated with dapagliflozin, there was no significant difference with patients on metolazone (0.56 kg; 95%CI: –0.06 to 1.19; P=0.082).
  • Both strategies also showed reductions in the secondary endpoints. However, there were no significant between-group differences at 48–96 hours in the mean change in sum of B-lines in 8 zones (–0.38; 95%CI: –2.09 to 1.32; P=0.67), pleural effusion score (–0.23; 95%CI: –0.88 to 0.42; P=0.48), loop diuretic efficiency (–0.08; 95%CI: –0.17 to 0.00; P=0.07), or modified ADVOR congestion score (0.21; 95%CI: –0.48 to 0.89; P=0.56).
  • Compared with metolazone, dapagliflozin was associated with smaller increases in creatinine and blood urea levels and smaller decreases in serum sodium and serum potassium levels.
  • With regard to adverse events, ketoacidosis or need for renal replacement therapy were not observed in either treatment group.
  • The mean cumulative IV furosemide dose was significantly higher in the dapagliflozin group compared with the metolazone group at 72 and 96 hours.


Although both diuretic strategies were effective in relieving congestion in HF patients with diuretic resistance, dapagliflozin was not more effective than metolazone. Dapagliflozin-treated patients received a larger cumulative dose of IV furosemide but showed less biochemical upset compared with metolazone-treated patients. Both strategies were well tolerated.

- Our reporting is based on the information provided at the ESC Heart Failure 2023 -

The results of this study were simultaneously published in Eur Heart J.

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