Effect of the use of dapagliflozin in diuresis, natriuriesis, and in ultrafiltration and peritoneal elimination of sodium in patients with refractory heart failure: DAPA-DP study

Abstract

Abstract Background Peritoneal dialysis (PD) has emerged as an effective technique for managing refractory heart failure (HF) in patients unresponsive to diuretics. Previous meta-analyses have demonstrated significant reductions in hospitalization days and improvements in cardiac function among patients with HF treated with PD compared with those receiving standard therapies. However, sodium retention remains a challenge in HF management, as patients often exhibit poor compliance with dietary sodium restrictions. In patients on PD, sodium retention exacerbates fluid overload and cardiovascular complications, highlighting the need for effective sodium elimination strategies. Methods This study will investigate the effects of PD on sodium excretion and its impact on mortality and heart failure exacerbations. We will enroll 31 patients with refractory HF in a continuous ambulatory peritoneal dialysis program. The study design includes randomization, a washout period, and an open-label approach to evaluate the impact of dapagliflozin, a sodium-glucose cotransporter-2(SGLT2) inhibitor, on sodium balance and clinical outcomes. Statistical analysis will be performed to assess changes in sodium excretion and the association between sodium removal levels and clinical outcomes. Expected results We hypothesize that dapagliflozin in patients undergoing PD will enhance net sodium loss by combining its known natriuretic efficacy with the hypothesis of increased sodium elimination in the peritoneal effluent. This effect is expected to be observed independently of the patients’ baseline renal function. Additionally, the study will investigate the safety profile of dapagliflozin in PD patients, monitoring for potential adverse effects and overall tolerability. Conclusions The study aims to provide valuable insights into optimizing HF management in PD patients through innovative therapeutic approaches. The anticipated findings could significantly impact clinical practice by improving sodium and fluid balance, potentially leading to reduced hospitalizations and better overall health outcomes for HF patients on PD. Trial Registration: This study was approved and authorized by both the Spanish Agency of Drugs and Health Products (AEMPS) and the Hospital Clínico Universitario de Valencia Ethical Committee (CEIM). The investigated drug, dapagliflozin, has received approval from the European Medicines Agency (EMA) and has been authorized for commercialization in Spain (CEIM FILE: 148/23, CODE: DAPA-DP, EUDRACT no.: 2023-505571-78-00).