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

Abstract

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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How to Cite
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 https://he01.tci-thaijo.org/index.php/JNST/article/view/258804
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Original Article

References

Ariyachaipanich A, Krittayaphong R, Kunjara Na Ayudhya R, Yingchoncharoen T, Buakhamsri A, Suvachittanont N. Heart Failure Council of Thailand (HFCT) 2019 Heart Failure Guideline: Introduction and Diagnosis. J Med Assoc Thai 2019;102:231-9.

Damman K, Testani JM. The kidney in heart failure: an update. Eur Heart J. 2015 Jun 14;36(23):1437-44.

Vinod P, Krishnappa V, Chauvin AM, Khare A, Raina R. Cardiorenal Syndrome: Role of Arginine Vasopressin and Vaptans in Heart Failure. Cardiol Res. 2017 Jun;8(3):87-95.

Goldsmith SR, Gheorghiade M. Vasopressin antagonism in heart failure. J Am Coll Cardiol. 2005 Nov 15;46(10):1785-91.

Gheorghiade M, Gattis WA, O’Connor CM, Adams KF Jr, Elkayam U, Barbagelata A, et al. Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure (ACTIV in CHF) Investigators. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial. JAMA. 2004; 291(16):1963-71.

Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007; 297(12):1319-31.

Wang C, Xiong B, Cai L. Effects of Tolvaptan in patients with acute heart failure: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2017; 17(1):164.

Tominaga N, Kida K, Inomata T, Sato N, Izumi T, Akashi YJ, et al. Effects of Tolvaptan Addition to Furosemide in Normo- and Hyponatremia Patients with Heart Failure and Chronic Kidney Disease Stages G3b-5: A Subanalysis of the K-STAR Study. Am J Nephrol. 2017;46(5):417-26.

Nielsen S, Terris J, Andersen D, Ecelbarger C, Frokiaer J, Jonassen T, et al Congestive heart failure in rats is associated with increased expression and targeting of aquaporin-2 water channel in collecting duct. Proc Natl Acad Sci U S A. 1997; 94(10):5450-5.

Jujo K, Saito K, Ishida I, Furuki Y, Kim A, Suzuki Y, et al. Randomized pilot trial comparing tolvaptan with furosemide on renal and neurohumoral effects in acute heart failure. ESC Heart Fail. 2016; 3(3):177-88.

Inomata T, Ikeda Y, Kida K, Shibagaki Y, Sato N, Kumagai Y, et al. Effects of Additive Tolvaptan vs. Increased Furosemide on Heart Failure With Diuretic Resistance and Renal Impairment- Results From the K-STAR Study. Circ J. 2017; 82(1):159-67.

Matsue Y, Ter Maaten JM, Suzuki M, Torii S, Yamaguchi S, Fukamizu S, et al. Early treatment with tolvaptan improves diuretic response in acute heart failure with renal dysfunction. Clin Res Cardiol. 2017; 106(10):802-12.