Comparison of the Tolvaptan Versus Furosemide-Based Diuretic Regimes in Patients Hospitalized for Heart Failure with Hyponatremia (AQUA-AHF)

Abstract

Introduction Hyponatremia is associated with worse longitudinal outcomes, and recently, poorer diuretic response in patients hospitalized for heart failure (HF). Whether tolvaptan monotherapy is a viable alternative to intravenous loop diuretics for decongestive therapy has not been tested. This study prospectively compared the efficacy and safety of a tolvaptan-based versus furosemide-based diuretic regimen on short-term outcomes in hyponatremic acute HF patients. Methods Prospective, randomized, open-label, parallel-group, pilot study comparing a tolvaptan-based versus conventional continuous infusion furosemide-based regimen. Thirty-three subjects requiring hospitalization for acute HF with evidence of volume overload, and a serum sodium Results Tolvaptan subjects were less often male (61 vs 93%) and had lower LVEF (24 vs 33%). Age, home diuretic dose, baseline serum sodium and vitals were not different. Four subjects in each group required study drug dose escalation (median daily dose throughout was tolvaptan 30mg and furosemide 120mg). Urine output and net fluid balance was not significantly different between tolvaptan or furosemide groups at 24h or any subsequent time point up to 96h. GFR tended to increase with tolvaptan, whereas it decreased with furosemide. Cystatin C improved at 24h with tolvaptan and the % change was significant compared to furosemide (-6.4±11.8 vs 4.1±17.2 % change, p=0.036). No significant between group differences were seen at 24h or study drug discontinuation/96h for NT-proBNP or PRA. As expected, serum sodium and potassium increased with tolvaptan compared to furosemide. Proportion with self-reported dyspnea that was moderately or markedly better at 24h was not different between groups (44% tolvaptan vs 27% furosemide, p=0.469). No major adverse events occurred. Conclusions Diuresis with tolvaptan was similarly effective compared to intravenous furosemide for acute HF. Tolvaptan was associated with signals for improved renal and electrolyte safety, however the clinical significance needs to be tested in a larger study.