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Efficacy and Safety of Tolvaptan in Heart Failure Patients with Volume Overload Despite the Standard Treatment with Conventional Diuretics: A Phase III, Randomized, Double-blind, Placebo-controlled Study (QUEST Study)

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Abstract

Purpose

Diuretics are recommended to treat volume overload with heart failure (HF), however, they may cause serum electrolyte imbalance, limiting their use. Moreover, patients with advanced HF could poorly respond to these diuretics. In this study, we evaluated the efficacy and safety of Tolvaptan, a competitive vasopressin V2-receptor antagonist developed as a new drug to treat volume overload in HF patients.

Methods

A phase III, multicenter, randomized, double-blind, placebo-controlled parallel study was performed to assess the efficacy and safety of tolvaptan in treating HF patients with volume overload despite the use of conventional diuretics. One hundred and ten patients were randomly assigned to receive either placebo or 15 mg/day tolvaptan for 7 consecutive days.

Results

Compared with placebo, tolvaptan administered for 7 days significantly reduced body weight and improved symptoms associated with volume overload. The safety profile of tolvaptan was considered acceptable for clinical use with minimal adverse effects.

Conclusion

Tolvaptan reduced volume overload and improved congestive symptoms associated with HF by a potent water diuresis (aquaresis).

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References

  1. Japanese Circulation Society. Guidelines for the diagnosis and treatment of cardiovascular disease (Joint Study Group Report 2009): guidelines for treatment of chronic heart failure (revised 2010). http://www.j-circ.or.jp/guideline/pdf/JCS2010_matsuzaki_h.pdf. Accessed 13 April 2011.

  2. Nohria A, Tsang SW, Fang JC, et al. Clinical assessment identifies hemodynamic profiles that predict outcomes in patients admitted with heart failure. J Am Coll Cardiol. 2003;41:1797–804.

    Article  PubMed  Google Scholar 

  3. Hunt SA, Abraham WT, Chin MH, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure). Circulation. 2005;112:e154–235.

    Article  PubMed  Google Scholar 

  4. Gupta S, Neyses L. Diuretic usage in heart failure: a continuing conundrum in 2005. Eur Heart J. 2005;26:644–9.

    Article  PubMed  CAS  Google Scholar 

  5. Raftery EB. Haemodynamic effects of diuretics in heart failure. Br Heart J. 1994;72(suppl):S44–7.

    Article  PubMed  CAS  Google Scholar 

  6. Multiple Risk Factor Intervention Trial Group. Baseline rest electrocardiographic abnormalities, antihypertensive treatment, and mortality in the Multiple Risk Factor Intervention Trial. Am J Cardiol. 1985;55:1–15.

    Article  Google Scholar 

  7. Cooper HA, Dries DL, Davis CE, Shen YL, Domanski MJ. Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction. Circulation. 1999;100:1311–5.

    PubMed  CAS  Google Scholar 

  8. Yamamura Y, Nakamura S, Itoh S, et al. OPC-41061, a highly potent human vasopressin V2-receptor antagonist: pharmacological profile and aquaretic effect by single and multiple oral dosing in rats. J Pharmacol Exp Ther. 1998;287:860–7.

    PubMed  CAS  Google Scholar 

  9. Gheorghiade M, Niazi I, Ouyang J, et al. Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation. 2003;107:2690–6.

    Article  PubMed  CAS  Google Scholar 

  10. Costello-Boerrigter LC, Smith WB, Boerrigter G, et al. Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure. Am J Physiol Ren Physiol. 2006;290:F273–8.

    Article  CAS  Google Scholar 

  11. Matsuzaki M, Masatsugu H, Izumi T, Asanoi H, Tsutamoto T, Tolvaptan Investigators. Effects of tolvaptan on volume overload in Japanese patients with heart failure: results of a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Cardiovasc Drugs Ther. 2011; e-pub ahead of print.

  12. Marsh JD, Smith TW. Piretanide: a loop-active diuretic. Pharmacology, therapeutic efficacy and adverse effects. Pharmacotherapy. 1984;4:170–80.

    PubMed  CAS  Google Scholar 

  13. Schrier RW, Gross P, Gheorghiade M, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355:2099–112.

    Article  PubMed  CAS  Google Scholar 

  14. Sterns RH, Cappuccio JD, Silver SM, Cohen EP. Neurologic sequelae after treatment of severe hyponatremia: a multicenter perspective. J Am Soc Nephrol. 1994;4:1522–30.

    PubMed  CAS  Google Scholar 

  15. Konstam MA, Gheorghiade M, Burnett Jr JC, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST outcome trial. JAMA. 2007;297:1319–31.

    Article  PubMed  CAS  Google Scholar 

  16. Gheorghiade M, Konstam MA, Burnett Jr JC, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST clinical status trials. JAMA. 2007;297:1332–43.

    Article  PubMed  CAS  Google Scholar 

  17. Fukunami M, Matsuzaki M, Hori M, et al. Efficacy and Safety of Tolvaptan in Heart Failure Patients with Sustained Volume Overload Despite the Use of Conventional Diuretics: A Phase III Open-label Study. Cardiovasc Drugs Ther. 2011; e-pub ahead of print.

  18. Inomata T, Izumi T, Matsuzaki M, et al. Phase III Clinical Pharmacology Study of Tolvaptan. Cardiovasc Drugs Ther. 2011; e-pub ahead of print.

  19. Udelson JE, McGrew FA, Flores E, et al. Multicenter, randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunction. J Am Coll Cardiol. 2007;49:2151–9.

    Article  PubMed  CAS  Google Scholar 

  20. Takaku F, Ogata E, Kurokawa K, Yazaki Y. New clinical internal medicine. 9th ed. Tokyo: Igaku-shoin Ltd.; 2009.

    Google Scholar 

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Disclosures

Editorial support for this manuscript was provided by Elsevier Japan K.K. This support was funded by Otsuka Pharmaceutical Co., Ltd.

Participating centers

The present study was conducted in the following institutions in Japan.

N.H.O. Hokkaido Cancer Center, N.H.O. Mito Medical Center, N.H.O. Takasaki National Hospital, N.H.O. Saitama National Hospital, N.H.O. Chiba Medical Center, N.H.O. Tokyo National Hospital, I.M.C.J. Toyama Hospital, N.H.O. Tokyo Medical Center, N.H.O. Yokohama Medical Center, N.H.O. Sagamihara National Hospital, N.H.O. Kanazawa Medical Center, N.H.O. Nagano National Hospital, N.H.O. Shizuoka Medical Center, N.H.O. Nagoya Medical Center, Toyota Memorial Hospital, N.H.O. Toyohashi Medical Center, N.H.O. Mie Chuo Medical Center, Sakurabashi Watanabe Hospital, Tazuke Kofukai Kitano Hospital, Osaka Red Cross Hospital, N.H.O. Osaka Medical Center, Osaka Rosai Hospital, N.H.O. Kobe Medical Center, N.H.O. Hamada Medical Center, N.H.O. Kure Medical Center, N.H.O. Fukuyama Medical Center, N.H.O. Higashihiroshima Medical Center, N.H.O. Kanmon Medical Center, N.H.O. Zentsuji National Hospital Kokura Memorial Hospital, N.H.O. Ureshino Medical Center, N.H.O. Nagasaki Medical Center, N.H.O. Nagasaki Medical Center Of Neurology, N.H.O. Kumamoto Medical Center, N.H.O. Beppu Medical Center, N.H.O. Matsumoto Medical Center, Kitasato Institute Hospital, Sanin Rosai Hospital, Chubu Tokushukai Hospital

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Correspondence to Masatsugu Hori.

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Matsuzaki, M., Hori, M., Izumi, T. et al. Efficacy and Safety of Tolvaptan in Heart Failure Patients with Volume Overload Despite the Standard Treatment with Conventional Diuretics: A Phase III, Randomized, Double-blind, Placebo-controlled Study (QUEST Study). Cardiovasc Drugs Ther 25 (Suppl 1), 33–45 (2011). https://doi.org/10.1007/s10557-011-6304-x

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