Administration of tolvaptan with reduction of loop diuretics ameliorates congestion with improving renal dysfunction in patients with congestive heart failure and renal dysfunction

Hanatani, Akihisa; Shibata, Atsushi; Kitada, Ryouko; Iwata, Shinichi; Matsumura, Yoshiki; Doi, Atsushi; Sugioka, Kenichi; Takagi, Masahiko; Yoshiyama, Minoru

doi:10.1007/s00380-016-0872-4

Cited by 28 publications

(15 citation statements)

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“…In recent years, they, in particular tolvaptan, have assumed major importance compared with conventional therapeutic approaches (water restriction or 3% hypertonic saline solution) for the treatment of hyponatremia [21,22,23,24,25,26,27] (see also Table 2). In Table 3, Table 4, Table 5 and Table 6, some characteristics of VRAs are outlined.…”

Section: The Vasopressin Receptor Antagonists (Vras): Promoting Frmentioning

confidence: 99%

RETRACTED: Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice?

Vecchis

Cantatrione

Mazzei

et al. 2016

JCM

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In the congestive heart failure (CHF) setting, chronic hyponatremia is very common. The present review aims at addressing topics relevant to the pathophysiology of hyponatremia in the course of CHF as well as its optimal treatment, including the main advantages and the limitations resulting from the use of the available dietary and pharmacological measures approved for the treatment of this electrolytic trouble. A narrative review is carried out in order to represent the main modalities of therapy for chronic hyponatremia that frequently complicates CHF. The limits of usual therapies implemented for CHF-related chronic hyponatremia are outlined, while an original analysis of the main advancements achieved with the use of vasopressin receptor antagonists (VRAs) is also executed. The European regulatory restrictions that currently limit the use of VRAs in the management of CHF are substantially caused by financial concerns, i.e., the high costs of VRA therapy. A thoughtful reworking of current restrictions would be warranted in order to enable VRAs to be usefully associated to loop diuretics for decongestive treatment of CHF patients with hyponatremia.

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Section: The Vasopressin Receptor Antagonists (Vras): Promoting Frmentioning

confidence: 99%

RETRACTED: Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice?

Vecchis

Cantatrione

Mazzei

et al. 2016

JCM

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“…22) Hanatani, et al also reported that the administration of TLV with lower doses of loop diuretics was clinically effective in improving congestion and renal dysfunction in patients with both congestive HF and renal dysfunction. 23) Overall, TLV appears to reduce the required dose of loop diuretics in patients with refractory HF.…”

Section: And Prognosis In Acute Heart Failurementioning

confidence: 94%

Tolvaptan Improves Prognosis in Responders with Acute Decompensated Heart Failure by Reducing the Dose of Loop Diuretics

Sunagawa

Kinugawa

2018

Int. Heart J.

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SummaryIt is unknown whether a response to tolvaptan (TLV) is related to prognosis in patients with acute decompensated heart failure (ADHF). We selected 25 patients as responders by their urinary response to TLV and by reduction of loop diuretics from 37 consecutive ADHF patients treated with TLV. As a control group, we selected 25 patients from 100 consecutive ADHF patients who were not treated with TLV by propensity score matching for age, serum sodium level, serum creatinine level, plasma B-type natriuretic peptide (BNP) level, systolic blood pressure, heart rate, and dose of loop diuretics. The primary outcome was defined as a composite endpoint of mortality and/or hemodialysis. The amount of loop diuretics administered to responders was reduced by TLV from 68.8 ± 26.2 mg to 30.4 ± 18.6 mg of furosemide equivalents per day, whereas the loop diuretic dose administered to non-responders was increased. The event-free survival of the TLV responders during 20 months was significantly better than that of the control group (95.8% versus 68.4%, P = 0.0406). The TLV responders, plasma BNP level, and estimated glomerular filtration rate were significantly related to the events in the Cox proportional hazard analysis. Patients with ADHF who respond to TLV may have a better prognosis than propensity-matched patients not receiving TLV treatment. In TLV responders, it may be possible to improve the patient's prognosis if the dose of loop diuretics can be reduced with TLV therapy.(Int Heart J 2018; 59: 87-93)

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“…Several clinical studies also investigated the effect of tolvaptan administered at 15 mg once daily in HF patients with renal dysfunction (eGFR 39, 32 and 12 mL/minute/1.73m 2 ); 9,19,20) however, the optimized dosage of tolvaptan has not been fully established. In the present study, the authors suggested that 7 mg (initial doses) and 10 mg (maintenance doses) of tolvaptan in HF patients with renal dysfunction (eGFR 41 mL/minute/ 1.73m 2 ) might be insufficient.…”

Section: )mentioning

confidence: 99%

New Insights Into Tolvaptan Treatment and the Renin-Angiotensin-Aldosterone System

Kida

2017

Int. Heart J.

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B ody fluids are regulated by the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system, and arginine vasopressin (AVP) in patients with congestive heart failure (HF). Angiotensin-converting enzyme inhibitors (ACE-I) have been shown to reduce mortality and morbidity in patients with HF and should be up-titrated to the maximum tolerated dose in order to achieve adequate inhibition of the RAAS.1) Angiotensin II receptor blockers (ARB) are recommended only as an alternative in patients intolerant of ACE-I. Meanwhile, tolvaptan, a vasopressin V2-receptor antagonist which inhibits vasopressin-mediated water reabsorption in the renal collecting duct 2) and leads to increased free water clearance (aquaresis),3) is available as a diuretic drug in the treatment of fluid accumulation in HF.4) Our recent pharmacokinetic and pharmacodynamic studies have reported the effectiveness and safety of add-on tolvaptan to furosemide in HF patients with advanced kidney dysfunction. 5,6) As compared with furosemide, tolvaptan in patients with acute HF is associated with comparable decongestion, better preservation of renal function, and less activation of the RAAS; 7) however, the efficacy of tolvaptan with or without ARB/ACE-I therapy in hospitalized patients with acute decompensated HF has not been fully investigated. The most recently published study of Adachi, et al 8) suggested that a single use of tolvaptan might induce an increase in urine volume in acute decompensated HF patients who were not previously treated with ARB/ACE-I. This result is quite surprising because ARB/ACE-I are the firstchoice drugs for the treatment of HF recommended by the guidelines.1) Their study retrospectively included 44 patients with acute decompensated HF who were treated with 7.0 mg (initial doses) of tolvaptan. The authors demonstrated that a response to the use of tolvaptan was independently associated with the non-use of ARB/ACE-I. They also reported single-use tolvaptan had an adequate diuretic effect on their study patients who did not receive ARB/ACE-I before the initiation of tolvaptan administration. Article p.385Several studies have reported on tolvaptan treatment and RAAS. Kadota, et al 9) provided new insights into the predictors of a response to tolvaptan using the AVP/plasma aldosterone concentration (PAC) ratio. Their study prospectively included 26 patients with decompensated HF who were treated with 15 mg of tolvaptan. They investigated the effects of tolvaptan on the RAAS and predictors for the response to tolvaptan treatment based on multiple laboratory factors, such as plasma renin activity, aldosterone concentration, and AVP. Imamura, et al 10) described the usefulness of the urine aquaporin (AQP) -2/AVP ratio for predicting the tolvaptan response. These results demonstrate that the potential ability to concentrate urine in the renal collecting duct is essential for the tolvaptan response. High urine osmolality basically indicates high secretion of AVP, although AVP alone cannot predict a response to tolvap...

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Administration of tolvaptan with reduction of loop diuretics ameliorates congestion with improving renal dysfunction in patients with congestive heart failure and renal dysfunction

Cited by 28 publications

References 32 publications

RETRACTED: Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice?

RETRACTED: Vasopressin Receptor Antagonists for the Correction of Hyponatremia in Chronic Heart Failure: An Underutilized Therapeutic Option in Current Clinical Practice?

Tolvaptan Improves Prognosis in Responders with Acute Decompensated Heart Failure by Reducing the Dose of Loop Diuretics

New Insights Into Tolvaptan Treatment and the Renin-Angiotensin-Aldosterone System

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