Skip to main content
SpringerLink
Log in

Use of tolvaptan vs. furosemide in older patients with heart failure

Meta-analysis of randomized controlled trials

Einsatz von Tolvaptan vs. Furosemid bei älteren Patienten mit Herzinsuffizienz

Metaanalyse randomisierter kontrollierter Studien

  • Original articles
  • Published:
Herz Aims and scope Submit manuscript

Abstract

Background

It is not known whether older patients with acute heart failure (HF) receiving tolvaptan have decreased mortality rates and a better long-term prognosis than patients who receive furosemide. We conducted a systematic review of randomized controlled trials (RCTs) to address this issue.

Methods

The Medline, Embase, and Cochrane Library databases were searched for English-language RCTs published before September 2016 comparing tolvaptan with furosemide treatment in older patients (>65 years old) after acute HF. The primary outcomes assessed were 6‑month all-cause mortality and worsening renal function (WRF); the secondary outcomes were electrolyte disorders, hospital readmissions, and adverse events.

Results

Out of 669 citations, six RCTs met the inclusion criteria for this meta-analysis. There was a significant decrease in WRF (relative risk [RR] = 0.67, 95% confidence interval [CI] = 0.52–0.86, p = 0.002) and in the hospitalization period (mean difference [MD] = −1.86, 95% CI = −3.70–−0.02, p = 0.05), as well as a significant increase in urine volume within 3 days of tolvaptan administration (MD = 1.59, 95% CI = 1.41–1.76, p < 0.00001). There were significant differences in creatinine levels between subgroups (MD = 0.33, 95% CI = 0.14–0.52, p = 0.0006). However, for the outcome of 6‑month all-cause mortality (RR = 0.56, 95% CI = 0.29–1.06, p = 0.07), there was no significant difference among all subgroups. There were significant differences in serum sodium concentration (MD = 0.68, 95% CI = 0.02–1.34, p = 0.04) but no significant changes in systolic blood pressure (MD = 3.57, 95% CI = −2.33–9.47, p = 0.24) between groups.

Conclusion

In older patients, tolvaptan relieves WRF, reduces the hospitalization period, and increases urine volume without significant effects on blood pressure. However, surprisingly, the use of tolvaptan did not influence 6‑month all-cause mortality.

Zusammenfassung

Hintergrund

Es ist nicht bekannt, ob ältere Patienten mit akuter Herzinsuffizienz unter Gabe von Tolvaptan eine geringere Mortalitätsrate und eine bessere Langzeitprognose als Patienten unter Gabe von Furosemid aufweisen. Die Autoren führten eine systematische Auswertung randomisierter kontrollierter Studien („randomized controlled trials“, RCT) durch, um die Frage zu klären.

Methoden

Die Datenbanken Medline, Embase und der Cochrane Library wurden nach englischsprachigen RCT durchsucht, die vor September 2016 publiziert worden waren und in denen die Tolvaptan- mit der Furosemidbehandlung bei älteren Patienten (>65 Jahre) nach akuter Herzinsuffizienz verglichen wurde. Primäre Endpunkte waren die 6‑Monats-Gesamtmortalität und eine sich verschlechternde Nierenfunktion („worsening renal function“, WRF); sekundäre Endpunkte waren Elektrolytstörungen, Wiederaufnahme ins Krankenhaus und unerwünschte Wirkungen.

Ergebnisse

Von 669 zitierten Arbeiten erfüllten 6 RCT die Einschlusskriterien dieser Metaanalyse. Es bestand eine signifikante Abnahme der WRF (relatives Risiko, RR: 0,67; 95%-Konfidenzintervall, 95%-KI: 0,52–0,86; p = 0,002) und der Verweildauer (Mittelwertdifferenz, MD: −1,86; 95%-KI: −3,70 bis −0,02; p = 0,05) sowie ein signifikanter Anstieg des Urinvolumens innerhalb von 3 Tagen nach Tolvaptangabe (MD: 1,59; 95%-KI: 1,41–1,76; p < 0,00001). Zwischen den Untergruppen zeigten sich signifikante Unterschiede beim Kreatininwert (MD: 0,33; 95%-KI: 0,14–0,52; p = 0,0006). Jedoch fand sich kein signifikanter Unterschied zwischen allen Untergruppen für die 6‑Monats-Gesamtmortalität (RR: 0,56; 95%-KI: 0,29–1,06; p = 0,07). Signifikante Unterschiede zwischen den Gruppen bestanden bei der Natriumkonzentration im Serum (MD: 0,68; 95%-KI: 0,02–1,34; p = 0,04), aber nicht beim systolischen Blutdruck (MD: 3,57; 95%-KI: −2,33 bis 9,47; p = 0,24).

Schlussfolgerung

Bei älteren Patienten führt Tolvaptan zur Verminderung der WRF, zur Senkung der Hospitalisierungsdauer und zur Steigerung des Urinvolumens ohne signifikante Wirkung auf den Blutdruck. Jedoch beeinflusste überraschenderweise die Gabe von Tolvaptan die Gesamtmortalität nach 6 Monaten nicht.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Hauptman PJ, Burnett J, Gheorghiade M, Grinfeld L, Konstam MA, Kostic D et al (2013) Clinical course of patients with Hyponatremiaand decompensated systolic heart failure and the effect of vasopressin receptor antagonism with tolvaptan. J Card Fail 19(6):390–397

    Article  PubMed  CAS  Google Scholar 

  2. Imamura T, Kinugawa K (2016) Urine aquaporin-2: a promising marker of response to the arginine vasopressin type-2 antagonist, tolvaptan in patients with congestive heart failure. Int J Mol Sci 17(1):E105

    Article  PubMed  CAS  Google Scholar 

  3. Zulkifli AH, Suridanda DS (2016) Tolvaptan: a novel diuretic in heart failure management. J Tehran Heart Cent 11(1):1–5

    Google Scholar 

  4. 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):1–13

    Article  PubMed  CAS  Google Scholar 

  5. Sakaida I, Yamashita S, Kobayashi T, Komatsu M, Sakai T, Komorizono Y et al (2013) Efficacy and safety of a 14-day administration of tolvaptan in the treatment ofpatients with ascites in hepatic oedema. J Int Med Res 41(3):835–847

    Article  PubMed  CAS  Google Scholar 

  6. Thajudeen B, Salahudeen AK (2016) Role of tolvaptan in the management of hyponatremia in patients with lung and other cancers: current data and future perspectives. Cancer Manag Res 8:105–114

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Kawaratani H, Fukui H, Yoshiji H (2016) Treatment for cirrhotic ascites. Hepatol Res 47(2):166. doi:10.1111/hepr.12769

    Article  PubMed  Google Scholar 

  8. Guler S, Cimen S, Hurton S, Molinari M (2015) Diagnosis and treatment modalities of symptomatic polycystic kidney disease. In: Li X (ed) Polycystic kidney disease. Codon Publications, Brisbane, pp 1–10

    Google Scholar 

  9. Gansevoort RT, Arici M, Benzing T, Birn H, Capasso G, Covic A et al (2016) Recommendations for the use of tolvaptan in autosomal dominant polycystic kidney disease: a position statement on behalf of the ERA-EDTA Working Groups on Inherited Kidney Disorders and European Renal Best Practice. Nephrol Dial Transplant 31(3):337–348

    Article  PubMed  PubMed Central  Google Scholar 

  10. Kimura K, Momose T, Hasegawa T, Morita T, Misawa T, Motoki H et al (2016) Early administration of tolvaptan preserves renal function in elderly patients with acutedecompensated heart failure. J Cardiol 67(5):399–405

    Article  PubMed  Google Scholar 

  11. Kinoshita M, Okayama H, Kawamura G, Shigematsu T, Takahashi T, Kawada Y et al (2016) Favorable effect of early administration of tolvaptanin elderlypatients with repeat hospitalizations for acute decompensated heart failure. J Am Coll Cardiol 67(13, Supplement):1426

    Article  Google Scholar 

  12. Matsue Y, Suzuki M, Torii S, Yamaguchi S, Fukamizu S, Ono Y et al (2016) Clinical effectiveness of tolvaptan in patientswith acute heartfailure and renal dysfunction. J Card Fail 22(6):423–432

    Article  PubMed  CAS  Google Scholar 

  13. Matsuzaki M, Hori M, Izumi T, Fukunami M (2011) Efficacy and safety of tolvaptan in heart failure patientswith volume overload despite the standard treatmentwith conventional diuretics: a phase III, randomized, double-blind, placebo-controlled study (QUEST study). Cardiovasc Drugs Ther 25(S1):S33–S45. doi:10.1007/s10557-011-6304-x

    Article  PubMed  CAS  Google Scholar 

  14. Uemura Y, Shibata R, Takemoto K, Uchikawa T, Koyasu M, Ishikawa S et al (2016) Clinical benefit of tolvaptan in patients with acute decompensatedheart failure and chronic kidney disease. Heart Vessel 31(10):1643–1649

    Article  Google Scholar 

  15. Matsue Y, Suzuki M, Seya M, Iwatsuka R, Mizukami A et al (2013) Tolvaptan reduces the risk of worsening renal function in patients with acute decompensated heart failure in high-risk population. J Cardiol 61(2):169–174

    Article  PubMed  Google Scholar 

  16. Gheorghiade M, Niazi I, Ouyang J, Czerwiec F, Kambayashi J, Zampino M et al (2003) Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation 107:2690–2696

    Article  PubMed  CAS  Google Scholar 

  17. Goldsmith SR (2016) A new approach to treatment of acute heart failure. J Cardiol 67(5):395–398

    Article  PubMed  Google Scholar 

  18. Foebel AD, Heckman GA, Ji K, Dubin JA, Turpie ID, Hussack P et al (2013) Heart failure – related mortality and hospitalization inthe year following admission toa long-term carefacility:the geriatric outcomes and longitudinal decline in heart failure (GOLD-HF) study. J Card Fail 19(7):468–477

    Article  PubMed  Google Scholar 

  19. Xiong B, Huang Y, Tan J, Yao Y, Wang C, Qian J et al (2015) The short-term and long-term effects of tolvaptan in patientswith heart failure: a meta-analysis of randomized controlled trials. Heart Fail Rev 20(6):633–642

    Article  PubMed  CAS  Google Scholar 

  20. Costello-Boerrigter LC, Smith WB, Boerrigter G, Ouyang J, Zimmer CA, Orlandi C et al (2006) Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium andpotassium excretion in human heart failure. Am J Physiol Renal Physiol 290(2):F273–F278

    Article  PubMed  CAS  Google Scholar 

  21. Abo-Salem E, Sherif K, Dunlap S, Prabhakar S (2014) Potential aetiologies and prognostic implications of worsening renal function in acute decompensated heart failure. Acta Cardiol 69(6):657–663

    Article  PubMed  Google Scholar 

  22. Gheorghiade M, Pang PS, Ambrosy AP, Lan G, Schmidt P, Filippatos G et al (2012) A comprehensive, longitudinal description of the in-hospitaland post-discharge clinical, laboratory, and neurohormonalcourse of patients with heart failure who die or are re-hospitalized within 90 days: analysis from the EVEREST trial. Heart Fail Rev 17(3):485–509

    Article  PubMed  Google Scholar 

  23. Imamura T, Kinugawa K, Minatsuki S, Muraoka H, Kato N, Inaba T et al (2013) Urine osmolality estimated using urine urea nitrogen, sodium and creatinine can effectively predict response to tolvaptan in decompensated heart failure patients. Circ J 77:1208–1213

    Article  PubMed  CAS  Google Scholar 

  24. Shanmugam E, Doss CR, George M, Jena A, Rajaram M, Ramaraj B et al (2016) Effect of tolvaptan on acute heart failure with hyponatremia – a randomized, double blind, controlledclinical trial. Indian Heart J 68:S15–S21. doi:10.1016/j.ihj.2015.07.006

    Article  PubMed  Google Scholar 

  25. Imamura T, Kinugawa K, Nitta D, Komuro I (2016) Tolvaptan reduces long-term total medical expenses and length of stay in aquaporin-defined responders. Int Heart J 57(5):593–599

    Article  PubMed  Google Scholar 

  26. Eguchi A, Iwasaku T, Okuhara Y, Naito Y, Mano T, Masuyama T et al (2016) Long-term administration of tolvaptan increases myocardial remodelingand mortality via exacerbation of congestion in mice heart failure modelafter myocardial infarction. Int J Cardiol 221:302–309

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 81170133 to J. Yang; Grant No. 81200088,81470387 to J. Yang), the Natural Science Foundation of Yichang City, China (Grant No.A12301-01), and Hubei Province’s Outstanding Medical Academic Leader Program, China.

Author information

Authors and Affiliations

  1. Institute of Cardiovascular Diseases, the First College of Clinical Medical Sciences, China Three Gorges University, 443000, Yichang, Hubei Province, China

    W.‑l. Huang MM,  Y. Yang MM,  J. Yang MD,  J. Yang MD, PhD,  H.‑b. Wang MM,  X.‑l. Xiong &  Y.‑f. Zhang MM

Authors
  1. W.‑l. Huang MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Yang MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Yang MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Yang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H.‑b. Wang MM
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. X.‑l. Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Y.‑f. Zhang MM
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to J. Yang MD or J. Yang MD, PhD.

Ethics declarations

Conflict of interest

W.-l. Huang, Y. Yang, J. Yang, J. Yang, H.-B. Wang, X.-l. Xiong, and Y.-f. Zhang declare that they have no competing interests.

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Wei-ling Huang and Ying Yang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, W., Yang, Y., Yang, J. et al. Use of tolvaptan vs. furosemide in older patients with heart failure. Herz 43, 338–345 (2018). https://doi.org/10.1007/s00059-017-4563-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00059-017-4563-4

Keywords

Schlüsselwörter

Search

Navigation