Benefit of add on low dose oral tolvaptan to loop diuretics among patients with acute decompensated heart failure: a randomized controlled trial

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Ratthaphon Chitthai
Jingjo Saisa-ard
Pitchamon Inkong
Amnart Chaiprasert
Naowanit Nata
Pamila Tasanavipas
Narittaya Varothai
Paramat Thimachai
Ouppatham Supasyndh
Bancha Satirapoj


Background: Arginine-vasopressin levels are elevated in acute decompensated heart failure (ADHF). Standard dose vasopressin antagonist increases free water clearance and improves ADHF symptoms. However, limited trials were conducted of low dose tolvaptan with standard loop diuretics in ADHF.

Objective: The study aimed to evaluate the effect of combining low dose oral tolvaptan and loop diuretics compared with standard dose loop diuretics in hospitalized ADHF.

Methods: A randomized, open-label, controlled trial was conducted among patients hospitalized with ADHF within 48 hours (N=40). The patients were randomly assigned to receive oral tolvaptan 7.5 mg once daily plus standard intravenous furosemide (n=20) or standard intravenous furosemide (n=20) for three days. The endpoints were changes in ADHF score, fluid balance, body weight, and plasma sodium from baseline up to 3 days.

Results: A total of 40 patients with ADHF completed the trial. Altogether, 52.5% were male and average serum creatinine was 1.73 ± 1.06 mg/dL. Compared with the control, tolvaptan add on therapy for 3 days improved ADHF score [mean difference -2.05 (95%CI -3.78 to -0.32)], increased urine output [mean difference 2,620 mL (95%CI 873.82 to 4,366.68), reduced body weight [mean difference -1.42 kg (95%CI -2.43 to -0.41)], and increased plasma sodium level [mean difference 3.75 mEq/L (95%CI 1.23 to 6.27)]. No differences were found in the cumulative dose of furosemide, changes in renal function, hypokalemia, and metabolic alkalosis between treatment and control groups.

Conclusion: Short term treatment with low dose tolvaptan (7.5 mg/day) added to standard therapy effectively improved ADHF symptoms, and fluid balance without worsening renal function or producing serious side effects.


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Chitthai, R., Saisa-ard, J., Inkong, P., Chaiprasert, A., Nata, N., Tasanavipas, P., Varothai, N., Thimachai, P., Supasyndh, O., & Satirapoj, B. (2022). Benefit of add on low dose oral tolvaptan to loop diuretics among patients with acute decompensated heart failure: a randomized controlled trial. Journal of the Nephrology Society of Thailand, 28(2), 50–59. Retrieved from
Original Article


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