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Different diuretic properties between tolvaptan and furosemide in congestive heart failure patients with diuretic resistance and renal impairment: a subanalysis of the K-STAR

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Abstract

We attempted to identify the difference in diuretic properties between tolvaptan (TLV) and furosemide (FUR) in congestive heart failure (CHF) patients with loop diuretic resistance and renal impairment. We investigated 81 CHF patients with loop diuretic treatment and renal impairment included in t he Kanagawa Aquaresis Investigators Trial of Tolvaptan on Heart Failure Patients with Renal Impairment (K-STAR). Predictive baseline factors and their changes during treatment periods were analyzed for correlation with percentage change in urine volume (%ΔUV) after additive introduction of TLV or increasing doses of FUR. Higher urine osmolality at baseline (β = 0.355; p = 0.033) in the TLV group and a lower ratio of blood urea nitrogen to serum creatinine (BUN/Cr, β = − 0.405; p = 0.020) in the FUR group were predictive of higher %ΔUV. Higher Δfree-water clearance (β = 0.667; p < 0.0001) in the TLV group, and higher %ΔBUN/Cr (β = 0.344; p = 0.030), higher %Δurine sodium concentration (β = 0.337; p = 0.037), and lower %Δstroke volume (β = − 0.390; p = 0.017) in the FUR group were correlated with %ΔUV. In conclusion, baseline urine osmolality and change in free-water clearance with additive introduction of TLV and a changing ratio of BUN/Cr with increasing doses of FUR were identified as key clinical parameters related to diuretic response.

Trial registration UMIN000009201.

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References

  1. Cody RJ (1993) Clinical trials of diuretic therapy in heart failure: research directions and clinical considerations. J Am Coll Cardiol 22:165a–171a

    Article  CAS  PubMed  Google Scholar 

  2. Leto L, Aspromonte N, Feola M (2014) Efficacy and safety of loop diuretic therapy in acute decompensated heart failure: a clinical review. Heart Fail Rev 19:237–246

    Article  CAS  PubMed  Google Scholar 

  3. Hasselblad V, Gattis Stough W, Shah MR, Lokhnygina Y, O'Connor CM, Califf RM, Adams KF Jr (2007) Relation between dose of loop diuretics and outcomes in a heart failure population: results of the ESCAPE trial. Eur J Heart Fail 9:1064–1069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Valente MA, Voors AA, Damman K, Van Veldhuisen DJ, Massie BM, O'Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Davison B, Cleland JG, Givertz MM, Bloomfield DM, Fiuzat M, Dittrich HC, Hillege HL (2014) Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J 35:1284–1293

    Article  CAS  PubMed  Google Scholar 

  5. ter Maaten JM, Dunning AM, Valente MA, Damman K, Ezekowitz JA, Califf RM, Starling RC, van der Meer P, O'Connor CM, Schulte PJ, Testani JM, Hernandez AF, Tang WH, Voors AA (2015) Diuretic response in acute heart failure—an analysis from ASCEND-HF. Am Heart J 170:313–321

    Article  CAS  PubMed  Google Scholar 

  6. Voors AA, Davison BA, Teerlink JR, Felker GM, Cotter G, Filippatos G, Greenberg BH, Pang PS, Levin B, Hua TA, Severin T, Ponikowski P, Metra M, Investigators RELAX-AHF (2014) Diuretic response in patients with acute decompensated heart failure: characteristics and clinical outcome—an analysis from RELAX-AHF. Eur J Heart Fail 16:1230–1240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. ter Maaten JM, Valente MA, Damman K, Hillege HL, Navis G, Voors AA (2015) Diuretic response in acute heart failure—pathophysiology, evaluation, and therapy. Nat Rev Cardiol 12:184–192

    Article  CAS  PubMed  Google Scholar 

  8. Momomura SI (2017) Tolvaptan. Is it a trump to worsening renal function? Circ J 81:642–644

    Article  CAS  PubMed  Google Scholar 

  9. Doggrell SA (2004) Tolvaptan (Otsuka). Curr Opin Investig Drugs 5:977–983

    CAS  PubMed  Google Scholar 

  10. Gheorghiade M, Konstam MA, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C (2007) Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA 297:1332–1343

    Article  CAS  PubMed  Google Scholar 

  11. Inomata T, Ikeda Y, Kida K, Shibagaki Y, Sato N, Kumagai Y, Shinagawa H, Ako J, Izumi T, Investigators Kanagawa Aquaresis (2017) Effects of additive tolvaptan vs. increased furosemide on heart failure with diuretic resistance and renal impairment—results from the K-STAR study. Circ J 82:159–167

    Article  PubMed  Google Scholar 

  12. Testani JM, Brisco MA, Turner JM, Spatz ES, Bellumkonda L, Parikh CR, Tang WH (2014) Loop diuretic efficiency: a metric of diuretic responsiveness with prognostic importance in acute decompensated heart failure. Circ Heart Fail 7:261–270

    Article  CAS  PubMed  Google Scholar 

  13. Imamura T, Kinugawa K, Shiga T, Kato N, Muraoka H, Minatsuki S, Inaba T, Maki H, Hatano M, Yao A, Kyo S, Nagai R (2013) Novel criteria of urine osmolality effectively predict response to tolvaptan in decompensated heart failure patients—association between non-responders and chronic kidney disease. Circ J 77:397–404

    Article  CAS  PubMed  Google Scholar 

  14. Okayama D, Suzuki T, Shiga T, Minami Y, Tsuruoka S, Hagiwara N (2015) Blood urea nitrogen/creatinine ratio and response to tolvaptan in patients with decompensated heart failure: a retrospective analysis. Am J Cardiovasc Drugs 15:289–293

    Article  CAS  PubMed  Google Scholar 

  15. Lindenfeld J, Schrier RW (2011) Blood urea nitrogen a marker for adverse effects of loop diuretics? J Am Coll Cardiol 58:383–385

    Article  CAS  PubMed  Google Scholar 

  16. Miyazaki T, Fujiki H, Yamamura Y, Nakamura S, Mori T (2007) Tolvaptan, an orally active vasopressin V(2)-receptor antagonist—pharmacology and clinical trials. Cardiovasc Drug Rev 25:1–13

    Article  CAS  PubMed  Google Scholar 

  17. Ambrosy A, Goldsmith SR, Gheorghiade M (2011) Tolvaptan for the treatment of heart failure: a review of the literature. Expert Opin Pharmacother 12:961–976

    Article  CAS  PubMed  Google Scholar 

  18. Ellison DH (2001) Diuretic therapy and resistance in congestive heart failure. Cardiology 96:132–143

    Article  CAS  PubMed  Google Scholar 

  19. Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE, Zannad F, Cook T, Ouyang J, Zimmer C, Orlandi C, Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) Investigators (2007) Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA 297:1319–1331

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the collaborators and members of the Kanagawa Aquaresis Investigators and investigators at clinical sites for enrolling study patients.[11] The K-STAR was supported by the Kidney Foundation, Japan. Clinical trial registration ID was assigned by the University hospital Medical Information Network (UMIN) as UMIN000009201.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan

    Yuki Ikeda & Junya Ako

  2. Department of Cardiovascular Medicine, Kitasato University Kitasato Institute Hospital, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8642, Japan

    Takayuki Inomata

  3. Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan

    Keisuke Kida

  4. Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan

    Yugo Shibagaki

  5. Internal Medicine and Cardiology, Nippon Medical School Musashi-Kosugi Hospital, Kawasaki, Japan

    Naoki Sato

  6. Niigata Minami Hospital, Niigata, Japan

    Tohru Izumi

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  1. Yuki Ikeda
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  2. Takayuki Inomata
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  3. Keisuke Kida
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  4. Yugo Shibagaki
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  6. Tohru Izumi
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  7. Junya Ako
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Kanagawa Aquaresis Investigators

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Correspondence to Takayuki Inomata.

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Conflict of interest

Dr. Takayuki Inomata received lecture honoraria from Otsuka Pharmaceutical Co. and Daiichi-Sankyo Pharmaceutical. Dr. Yugo Shibagaki received lecture honoraria from Otsuka Pharmaceutical and Novartis Pharma; and research funding from Otsuka Pharmaceutical, Teijin Pharma and Kyowa-Hakko Kirin. Dr. Naoki Sato received consultancy fees from Novartis and Terumo; lecture honoraria from Otsuka, Daiichi-Sankyo, Ono, Eisai, Bayer, Boehringer-Ingelheim, Roche Diagnostics-Japan, Astellas, and Teijin; and research supports to institution from Roche-Japan and Astellas. The other authors have nothing to disclose.

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Ikeda, Y., Inomata, T., Kida, K. et al. Different diuretic properties between tolvaptan and furosemide in congestive heart failure patients with diuretic resistance and renal impairment: a subanalysis of the K-STAR. Heart Vessels 34, 442–451 (2019). https://doi.org/10.1007/s00380-018-1270-x

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  • DOI: https://doi.org/10.1007/s00380-018-1270-x

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