Clinical utility of tolvaptan in the management of hyponatremia in heart failure patients

Figures & data

Figure 1 Hyponatremia and prognosis in heart failure patients.

Abbreviation: LOS, length of stay.

Table 1 Tolvaptan clinical trials in heart failure

Study	No. of patients and characteristics	Dosage	Primary endpoint	Results and comments	Adverse effects
Gheorghiade et al^Citation24	N = 254 Pts with CHF in outpatient setting (NYHA class I–IV) and volume overload	Tolvaptan (30, 45 or 60 mg/day) for 25 days vs placebo	Decrease in body weight	Significant decrease in body weight in all tolvaptan groups at 24 h, with a concomitant increase in urine volume, lower urine osmolality and urinary sodium concentration	Dry mouth, thirst and polyuria
ACTIV in CHF^Citation25	N = 319 Pts with EF ≤ 40% hospitalized for congestive HF	Tolvaptan (30, 60 or 90 mg/day) for up to 60 days vs placebo	In hospital end-point: change in body weight at 24 hrs Outpatient end-point: worsening heart failure at 60 days after randomization	Dose independent decrease in body weight at 24 h in tolvaptan group No differences in worsening HF at 60 days	Thirst and dry mouth, dizziness, nausea, hypotension
SALT-1 and SALT-2^Citation28	N1 = 205 N2 = 243 CHF and other hospitalized pts with euvolemic or hypervolemic hyponatremia	Tolvaptan (15–60 mg/day) for 30 days vs placebo	Change in serum sodium concentrations (from baseline to 4th and to 30th day)	Serum sodium concentrations Increased significantly more with tolvaptan during the first 4 days (P < 0.001) and after the full 30 days of therapy (P < 0.001)	Thirst and dry mouth, urinary frequency
Udelson^Citation29	N = 240 Pts with HF (NYHA class II/III) and EF ≤ 30%	Tolvaptan (30 mg/day) for 1 year vs placebo	To evaluate the effect of long-term administration of tolvaptan on left ventricular remodeling	There was no difference on LV volumes *post hoc analysis: improvement survival in tolvaptan group	Urinary frequency, thirst and dry mouth
EVEREST Clinical Status Trial^Citation31	N = 4133 Pts with EF ≤ 40%, NYHA class III/IV, hospitalized for worsening CHF	Tolvaptan (30 mg/day) for a minimum of 60 days vs placebo	Change in global clinical status Change in body weight at 7 days or at discharge	Oral tolvaptan in addition to standard therapy improved many, though not all, heart failure signs and symptoms, without serious adverse events	Thirst and dry mouth
EVEREST Outcome Trial^Citation32	N = 4133 Pts with EF ≤ 40%, NYHA class III/IV, hospitalized for worsening CHF	Tolvaptan (30 mg/day) for a minimum of 60 days vs placebo	All-cause mortality Composite of cardiovascular death or hospitalization for HF	No effect (either favorable or unfavorable) of long term tolvaptan treatment	Thirst and dry mouth

Abbreviations: CHF, chronic heart failure; EF, ejection fraction; HF, heart failure; LV, left ventricular; NHYA, New York Heart Association.

Figure 2 Changes in serum sodium level (EVEREST trial).

GheorghiadeMNiaziIOuyangJCzerwiecFKambayashiJOrlandiCTolvaptan investigatorsVasopressin receptor blockade in patients with congestive heart failure: results from a randomized, double-blind studyCirculation20031072690269612742979

 PubMed Web of Science ®Google Scholar

GheorghiadeMGattisWAO’ConnorCMAcute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure (ACTIV in CHF) InvestigatorsEffects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trialJAMA20042911963197115113814

 PubMed Web of Science ®Google Scholar

SchrierRWGrossPGheorghiadeMTolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremiaN Engl J Med2006552099211217105757

 PubMed Web of Science ®Google Scholar

UdelsonJEMcGrewFFloresEMulticenter randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunctionJ Am Coll Cardiol2007492151215917543634

 PubMed Web of Science ®Google Scholar

GheorghiadeMKonstamMABurnettJCJrEfficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) InvestigatorsShort-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status TrialsJAMA20072971332134317384438

 PubMed Web of Science ®Google Scholar

KonstamMAGheorghiadeMBurnettJCJrEfficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) InvestigatorsEffects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome TrialJAMA20072971319133117384437

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