Vasopressin receptor antagonists for the treatment of heart failure: a systematic review and meta-analysis of randomized controlled trials

Nistor, Ionuţ; Bararu, Iris; Apăvăloaie, Maria-Cristina; Voroneanu, Luminița; Donciu, Mihaela-Dora; Kanbay, Mehmet; Nagler, Evi; Covic, Adrian

doi:10.1007/s11255-014-0855-2

Cited by 8 publications

(4 citation statements)

References 37 publications

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“…Although previous RCTs and systematic reviews [ 7 – 10 ] reported treatment benefits of tolvaptan on patients with CHF, the optimal dosage remains unclear. This is because traditional meta-analysis can only make pairwise comparisons and is not well suited to compare multiple treatments, such as different dosages of the same drug.…”

Section: Introductionmentioning

confidence: 99%

Effects and safety of oral tolvaptan in patients with congestive heart failure: A systematic review and network meta-analysis

Chen

et al. 2017

PLoS ONE

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AimsSeveral studies reported treatment benefits of tolvaptan in patients with congestive heart failure (CHF). However, the optimal dosage remains unclear. We aimed to compare different dosage of tolvaptan to determine the optimal dosage in terms of the efficacy and safety.MethodsWe searched MEDLINE, PubMed, EMBASE, Cochrane CENTRAL and ClinicalTrials.gov through Aug 31, 2016. Randomized controlled trials (RCTs) comparing tolvaptan of different dosages or to placebo in patients with CHF were included. We used network meta-analysis to look for the optimal dosage in terms of effectiveness and safety. Urine output, body weight change and change in serum sodium were the main outcomes of efficacy. Adverse effects were the secondary outcomes. Quality was assessed by Cochrane risk-of-bias tool.ResultsTwelve RCTs reporting 14 articles with 5793 patients (mean age, 65.7 ± 11.9 years; 73.7% man) were included. Compared with placebo, the tolvaptan 30 mg had similar effects to tolvaptan 45–90 mg in terms of urine output (mean difference [MD] 2.03 liter; 95% confidence interval [CI] 1.3 to 2.71), body weight change (MD -1.12 kg; 95% CI -1.37 to -0.88) and change in serum sodium (MD 3.06 meq/L; 95% CI 2.43 to 3.68). Compared with placebo, tolvaptan of different dosage showed a non-significant higher risk of adverse effects.ConclusionsThese findings suggest that tolvaptan 30 mg and 45 mg may be the optimum dosage for CHF patients, because of its ability to provide favourable clinical results without greater adverse effects. However, tolvaptan is not beneficial for reducing all-cause mortality in CHF patients.

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Section: Introductionmentioning

confidence: 99%

Effects and safety of oral tolvaptan in patients with congestive heart failure: A systematic review and network meta-analysis

Chen

et al. 2017

PLoS ONE

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“…To date, vaptans have demonstrated an effect on [Na + ] serum [ 47 , 48 ], but no systematic review and meta-analysis has confirmed the clinical impact of this effect in both worsening HF [ 49 , 50 , 51 , 52 , 53 ] and cirrhotic ascites [ 54 , 55 , 56 ]. Importantly, although these drugs are used after water restriction and diuretics, only some molecules have been studied clinically, and only two vaptans are actually used in the clinic.…”

Section: Discussionmentioning

confidence: 99%

Correction of Hyponatremia May Be a Treatment Stratification Biomarker: A Two-Stage Systematic Review and Meta-Analysis

Herrera‐Gómez

Monge-Donaire

Ochoa-Sangrador

et al. 2018

JCM

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Changes in serum sodium concentration ([Na+]serum) can permit evaluation of the treatment effect of vasopressin antagonists (vaptans) in patients with worsening heart failure (HF) or cirrhotic ascites; that is, they may act as a treatment stratification biomarker. A two-stage systematic review and meta-analysis were carried out and contextualized by experts in fluid resuscitation and translational pharmacology (registration ID in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42017051440). Meta-analysis of aggregated dichotomous outcomes was performed. Pooled estimates for correction of hyponatremia (normalization or an increase in [Na+]serum of at least 3–5 mEq/L) under treatment with vaptans (Stage 1) and for clinical outcomes in both worsening HF (rehospitalization and/or death) and cirrhotic ascites (ascites worsening) when correction of hyponatremia is achieved (Stage 2) were calculated. The body of evidence was assessed. Correction of hyponatremia was achieved under vaptans (odds ratio (OR)/95% confidence interval (95% CI)/I2/number of studies (n): 7.48/4.95–11.30/58%/15). Clinical outcomes in both worsening HF and cirrhotic ascites improved when correction of hyponatremia was achieved (OR/95% CI/I2/n: 0.51/0.26–0.99/52%/3). Despite the appropriateness of the study design, however, there are too few trials to consider that correction of hyponatremia is a treatment stratification biomarker. Patients with worsening HF or with cirrhotic ascites needing treatment with vaptans, have better clinical outcomes when correction of hyponatremia is achieved. However, the evidence base needs to be enlarged to propose formally correction of hyponatremia as a new treatment stratification biomarker. Markers for use with drugs are needed to improve outcomes related to the use of medicines.

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“…Therefore, these findings of TLV are not attributed to the hemodynamics, but they are due to the effects of neurohormonal factors induced by vasopressin. The effectiveness of the long-term use of TLV in all HF patients was denied by the large-scale EVEREST trial and a meta-analysis (19, 20). Similarly, conivaptan, a V1a and V2 receptor antagonist that is approved only in the USA, shows no long-term benefits (21).…”

Section: Vasopressin and Chronic Hfmentioning

confidence: 99%

“…The safety and effectiveness of using TLV for children has been reported as well (48), so hypernatremia may be able to be avoided by the long-term use of TLV if we identify groups at high risk of hypernatremia and initiate TLV at relatively low doses, such as 3.75 mg/day. Although a meta-analysis reported in 2017 that TLV was not associated with an increased risk of adverse events (49), one report has claimed that the long-term use of TLV increased the risk of adverse events by 14% (20). The risk of adverse events should be evaluated when considering the continued use of TLV (especially in the long term).…”

Section: Safety Of Tlvmentioning

confidence: 99%

Hemodynamic and Hormonal Effects of Tolvaptan for Heart Failure

Kiuchi

Ikeda

2019

Intern. Med.

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Tolvaptan (TLV) is a diuretic agent administrated for heart failure (HF) only in Japan. Many clinical findings have been obtained from the accumulation of clinical experience, and the administration of TLV reportedly avoids causing a reduction in the renal function. In addition, TLV has been reported to exert effects other than diuresis. The early start of TLV after hospitalization shortens the length of the hospital stay, and continuous TLV after discharge extends the period until re-hospitalization of HF patients. TLV is thought to function via vasopressin V2 receptor antagonism. However, no significant differences in the long-term prognosis were noted between the group using TLV and not using TLV in the EVEREST trial, and effects other than diuresis are not useful for all HF patients. Therefore, it is necessary to identify patients who may experience effects other than diuresis with TLV administration. The accumulation of more patients and findings from further large-scale clinical trials will be necessary in order to clarify these points.

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Vasopressin receptor antagonists for the treatment of heart failure: a systematic review and meta-analysis of randomized controlled trials

Abstract: Vasopressin receptors antagonists may reduce body weight and increase Na but do not improve all-cause mortality, cardiovascular mortality or kidney function. In addition, acceptability of long-term treatment side effects and hospitalization appears problematic.

Cited by 8 publications

References 37 publications

Effects and safety of oral tolvaptan in patients with congestive heart failure: A systematic review and network meta-analysis

Effects and safety of oral tolvaptan in patients with congestive heart failure: A systematic review and network meta-analysis

Correction of Hyponatremia May Be a Treatment Stratification Biomarker: A Two-Stage Systematic Review and Meta-Analysis

Hemodynamic and Hormonal Effects of Tolvaptan for Heart Failure

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