Effects of Dapagliflozin in Patients with Heart Failure and Deterioration of Kidney Function Below eGFR 25 ml/min/1.73m²: A Participant Level Pooled Analysis of the DAPA-HF and DELIVER Trials

Presented at the ESC Congress 2023 by: Scott Solomon, MD - Boston, MA, USA

Introduction and methods

The combination of HF and CKD is associated with increased clinical risk as well as treatment hesitancy among physicians who are uncertain about the efficacy and safety of therapies when patients with HF experience deterioration in kidney function.

The previous DAPA-HF and DELIVER trials demonstrated consistent efficacy and safety of dapagliflozin over a wide range of kidney function. DAPA-HF excluded patients with eGFR<30 ml/min/1.73m² and DELIVER with eGFR <25ml/min/1.73m². However, protocols did not mandate discontinuation of the study drug if the eGFR fell below the threshold for patient inclusion.

The current study was a participant level pooled analysis of the DAPA-HF and DELIVER trials to investigate the prognostic implications of a deterioration in eGFR below 25 ml/min/1.73m². It also evaluated the association between deterioration in eGFR below 25 ml/min/1.73m², treatment with dapagliflozin and clinical outcomes in patients with chronic HF.

Main results

Efficacy outcomes

- The incidence of the primary composite outcome of CV death or worsening HF was nearly twice as high in patients who experienced a deterioration in eGFR <25 ml/min/1.73m², compared to those whose eGFR did not deteriorate below this value (HR 1.87, 95%CI 1.48-2.35, P<0.001).

- The incidence of the primary endpoint was lower in patients treated with dapagliflozin compared with placebo, regardless of whether patients experienced (HR 0.53; 95% CI: 0.33-0.83) or did not experience a deterioration (HR 0.78; 95% CI: 0.72-0.86) in eGFR below 25 ml/min/1.73m² (P for interaction = 0.17). The absolute risk reduction was higher among patients who experienced such deterioration compared to those who did not (ARR 10.7 vs. 2.4 per 100p-y)

Safety outcomes

- Rates of SAE and AE of interest (AE leading to drug discontinuation, AE leading to drug interruption, AE volume depletion and renal AE) were higher among patients who experienced a eGFR deterioration<25 ml/min/1.73m², compared to those who did not. However, safety outcomes remained similar between treatment groups, irrespective of deterioration in eGFR <25 ml/min/1.73m².

Conclusion

Patients with HF who experience a deterioration in eGFR below 25 ml/min/1.73m² are at higher risk of CV outcomes, compared with patients who do not experience such a deterioration. Compared with placebo, dapagliflozin reduced the risk of CV death or worsening HF regardless of whether patients experienced or did not experience a deterioration in eGFR below 25 ml/min/1.73m². “The benefit-to-risk ratio may favor continued treatment with dapagliflozin in patients with HF and deterioration in kidney function below eGFR below 25 ml/min/1.73m²” said Scott Solomon.

• Our reporting is based on the information provided at the ESC Congress 2023 -

mThe results of this study were simultaneously published in J. Am. Coll. Cardiol.