Effect of tolvaptan on acute heart failure with hyponatremia – A randomized, double blind, controlled clinical trial

Shanmugam, Elangovan; Doss, C R Madhu Prabhu; George, Melvin; Jena, Ajay Kumar; Rajaram, Muthukumar; Ramaraj, Balaji; Anjaneyan, Karthik; Kanagesh, B.

doi:10.1016/j.ihj.2015.07.006

Cited by 30 publications

(30 citation statements)

References 21 publications

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“…Diuretic therapy was prescribed by 12 studies [ 26 , 28 ]. Five RCTs [ 11 , 12 , 18 , 19 , 25 ] were performed exclusively in patients with acute decompensated heart failure (ADHF), whereas 7 RCTs [ 20 , 21 , 23 , 24 , 26 – 28 ] were conducted in patients with CHF. Six trials evaluated the urine output after tolvaptan treatment [ 11 , 12 , 18 , 20 , 24 , 26 ].…”

Section: Resultsmentioning

confidence: 99%

“…Eight trials evaluated the body weight loss after tolvaptan treatment [ 11 , 12 , 18 – 21 , 23 , 26 ]. Change of serum sodium was reported in 8 trials [ 11 , 12 , 18 – 20 , 25 , 26 , 28 ]. The safety of tolvaptan was evaluated by the occurrence of mortality, thirsty, renal failure, and adverse events.…”

Section: Resultsmentioning

confidence: 99%

“…Network meta-analysis also suggested that tolvaptan 30 mg to 90 mg had similar effects on increase of serum sodium. Four trials reported the incidence of hypernatremia, ranging from 0.5–8% in the tolvaptan group [ 12 , 19 , 22 , 25 ].…”

Section: Resultsmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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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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“…In fact, tolvaptan, a vasopressin type 2 receptor antagonist, shows an increase in serum sodium levels in ADHF with hyponatremia. 22 Ultrafiltration can remove a higher amount of sodium in addition to isotonic fluid in contrast to diuretics treatment which only removes hypotonic fluid. Theoretically, if patients had only dilutional hyponatremia, a more favorable water and salt balance can be achieved by ultrafiltration.…”

Section: Discussionmentioning

confidence: 99%

Impact of Ultrafiltration on Serum Sodium Homeostasis and its Clinical Implication in Patients With Acute Heart Failure, Congestion, and Worsening Renal Function

Kitai

Grodin

Kim

et al. 2017

Circ: Heart Failure

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Background The relationship between changes in serum sodium with clinical events in acute heart failure patients using different decongestive events has not been investigated. This study aimed to describe changes in serum sodium levels during decongestion therapy in patients receiving stepped pharmacologic therapy versus ultrafiltration. Methods and Results We studied 188 patients who were enrolled in the Cardiorenal Rescue Study in Acute Decompensated Heart Failure (CARRESS) trial. Treatment-induced hyponatremia (TIH) was defined as admission normonatremia (≥135 mEq/L) with a subsequent decrease (<135 mEq/L) during hospitalization. Patients treated with ultrafiltration had significantly lower sodium levels than those with conventional treatment at days 1, 4 and 7 (all P<0.01), while those at day-30 were similar between the groups. Changes in sodium levels in patients with ultrafiltration were negatively correlated to those in serum creatinine and plasma renin activity. The incidence of TIH was significantly higher in the ultrafiltration group than those receiving conventional treatment (P=0.002). Although patients with discharge hyponatremia had a higher risk for composite endpoint of all-cause death, re-hospitalization or unscheduled hospital visit in comparison to those without (adjusted hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.03–2.65; P=0.037), the risk was comparable between patients with TIH and those who did not experience any hyponatremia (adjusted HR, 0.93; 95%CI, 0.57–1.51; P=0.76). Conclusion Fluid removal by ultrafiltration was associated with a decrease in serum sodium levels compared to diuretic treatment, but returned to baseline levels at day-30. Discharge hyponatremia but not TIH was associated with worse clinical outcomes.

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“…Nevertheless, several hard issues preventing drug evaluation using biomarkers need to be solved [ 10 ]. With the aim to elucidate whether correction of hyponatremia is a treatment stratification biomarker [ 11 ], a two-stage systematic review and meta-analysis were performed to summarize the efficacy of the V 1A /V 2 -receptor antagonist conivaptan [ 12 , 13 , 14 , 15 ] and the V 2 -receptor antagonists lixivaptan [ 16 , 17 , 18 , 19 , 20 ], satavaptan [ 21 , 22 , 23 ] and tolvaptan [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ] in relation to changes in [Na + ] serum in patients with worsening HF or cirrhotic ascites.…”

Section: Introductionmentioning

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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Effect of tolvaptan on acute heart failure with hyponatremia – A randomized, double blind, controlled clinical trial

Abstract: Tolvaptan at a dose of 15mg is effective in reversing hyponatremia in acute heart failure and may be a suitable option in these patients.

Cited by 30 publications

References 21 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

Impact of Ultrafiltration on Serum Sodium Homeostasis and its Clinical Implication in Patients With Acute Heart Failure, Congestion, and Worsening Renal Function

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

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