Tolvaptan Add-On Intravenous Furosemide Therapy in Patients with Acute Heart Failure and CKD: A Randomized Controlled Trial

Background: Managing volume overload in acute heart failure (AHF) with chronic kidney disease (CKD) is challenging due to diuretic resistance and risk of acute kidney injury. Tolvaptan promotes aquaresis without significant nephrotoxicity, but its efficacy and safety in CKD patients remain unclear. Methods: Patients with CKD stage 3 or 4 hospitalized for heart failure were randomized 1:1 to receive furosemide with or without tolvaptan. Tolvaptan was initiated within 24 hours of admission at a starting dose of 7.5 mg/day and continued for three days. Furosemide dosing was adjusted at the physician’s discretion based on congestion. Outcomes included the incidence of acute kidney injury, cumulative diuresis, improvement in congestion score, and adverse events. Results: A total of 56 patients were randomized to receive either furosemide alone (n=29) or furosemide with tolvaptan (n=27). There were no significant differences between groups in the incidence of acute kidney injury, changes in serum creatinine, or cumulative furosemide dose. However, patients in the tolvaptan group showed significantly greater improvement in composite congestion scores (median 13 vs. 10, p=0.003) and achieved a more negative fluid balance (median −6.14 L vs. −3.95 L, p=0.047). The incidence of electrolyte disturbances including hyponatremia, hypernatremia, hypokalemia, and hyperkalemia was comparable between groups. Conclusion: Tolvaptan as an add-on to furosemide in patients with heart failure and CKD stage 3–4 significantly improved decongestion without increasing the risk of acute kidney injury or electrolyte disturbances. Funding: Government Support – Non-U.S. Outcome - Furosemide (n = 29) Furosemide with tolvaptan (n = 27) p-value Incidence of acute kidney injury 21 (72.4) 23 (88.5) 0.185 Change in serum creatinine, mg/dl 0.4±0.6 0.3±0.5 0.71 Improve in composite congestion score (IQR) 10 (7, 13) 13 (11.2, 13) 0.003 Negative fluid balance, L (IQR) 3.95 (1.85, 6.28) 6.14 (3.84, 8.03) 0.047 Cumulative furosemide dose, mg (IQR) 580 (460, 970) 960 (510, 1362) 0.083 Hyponatremia, n (%) 13 (44.8) 15 (57.7) 0.44 Hypernatremia, n (%) 2 (6.9) 4 (15.4) 0.41 Hypokalemia, n (%) 17 (58.6) 14 (53.8) 0.79 Hyperkalemia, n (%) 2 (6.9) 0 0.49