Dapagliflozin not better than metolazone at relieving congestion in HF patients with loop diuretic resistance

A recent study published in European Heart Journal showed a randomized trial comparing the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin to the thiazide-like diuretic metolazone found similar effects on diuretic response in patients hospitalized for heart failure. The study investigated the decongestive effects of these medications in patients resistant to treatment with intravenous furosemide.

The study conducted by Su Ern Yeoh and a team of researchers conducted an open-label trial involving multiple centres and randomized 61 patients to receive either dapagliflozin 10 mg once daily or metolazone 5-10 mg once daily for a 3-day treatment period. The primary

endpoint was the diuretic effect, assessed by the change in weight. Secondary endpoints included changes in pulmonary congestion, loop diuretic efficiency, and volume assessment score.

● The cumulative dose of furosemide at 96 hours was higher in the dapagliflozin group (976 ± 492 mg) compared to the metolazone group (704 ± 428 mg).

● The decrease in weight at 96 hours was similar between the two groups (3.0 ± 2.5 kg with dapagliflozin vs. 3.6 ± 2.0 kg with metolazone).

● The difference in weight change between the groups was not statistically significant (mean difference 0.65 kg, 95% confidence interval -0.12 to 1.41 kg, p=0.11).

● Loop diuretic efficiency was lower with dapagliflozin compared to metolazone.

● Changes in pulmonary congestion and volume assessment score were similar between the two treatments.

Patients receiving dapagliflozin experienced smaller changes in plasma sodium and potassium levels and smaller increases in urea and creatinine compared to those receiving metolazone. The incidence of serious adverse events was similar between the two treatment groups.

The study findings indicate that dapagliflozin and metolazone had comparable effects on relieving congestion in patients with heart failure and resistance to loop diuretics. Although patients in the dapagliflozin group received a higher cumulative dose of furosemide, they experienced less biochemical upset compared to those in the metolazone group. These results suggest that dapagliflozin may be a viable alternative in heart failure patients who are resistant to traditional diuretic therapy.

The study sheds light on the potential role of dapagliflozin, an SGLT2 inhibitor, in the management of heart failure patients with diuretic resistance. While it did not demonstrate superior diuretic efficacy compared to metolazone, dapagliflozin exhibited favourable effects on biochemical parameters. Healthcare professionals should consider individual patient characteristics and treatment goals when selecting diuretic therapies for heart failure patients with resistance to loop diuretics.

Further research is needed to explore the long-term effects and safety profile of dapagliflozin in this patient population. Understanding the potential benefits and risks of different diuretic strategies can contribute to improved management and outcomes for individuals with heart failure.

Reference:

Ern Yeoh, S., Osmanska, J., Petrie, M. C., Brooksbank, K. J. M., Clark, A. L., Docherty, K. F., Foley, P. W. X., Guha, K., Halliday, C. A., Jhund, P. S., Kalra, P. R., McKinley, G., Lang, N. N., Lee, M. M. Y., McConnachie, A., McDermott, J. J., Platz, E., Sartipy, P., Seed, A., … Campbell, R. T. (2023). Dapagliflozin versus metolazone in heart failure resistant to loop diuretics. European Heart Journal. https://doi.org/10.1093/eurheartj/ehad341