Clinical course of patients with hyponatremia and decompensated systolic heart failure and the effect of vasopressin receptor antagonism with tolvaptan

J Card Fail. 2013 Jun;19(6):390-7. doi: 10.1016/j.cardfail.2013.04.001. Epub 2013 May 14.

Abstract

Background: Patients with decompensated heart failure, volume overload, and hyponatremia are challenging to manage. Relatively little has been documented regarding the clinical course of these patients during standard in-hospital management or with vasopressin antagonism.

Methods and results: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan database was examined to assess the short-term clinical course of patients hospitalized with heart failure and hyponatremia and the effect of tolvaptan on outcomes. In the placebo group, patients with hyponatremia (serum Na(+) <135mEq/L; n = 232), compared with those with normonatremia at baseline (n = 1785), had less relief of dyspnea despite receiving higher doses of diuretics (59.2% vs 69.2% improved; P < .01) and worse long-term outcomes. In the hyponatremia subgroup from the entire trial cohort (n = 475), tolvaptan was associated with greater likelihood of normalization of serum sodium than placebo (58% vs 20% and 64% vs 29% for day 1 and discharge, respectively; P < .001 for both comparisons), greater weight reduction at day 1 and discharge (0.7 kg and 0.8 kg differences, respectively; P < .001 and P = .008), and greater relief of dyspnea (P = .03). Among all hyponatremic patients, there was no effect of tolvaptan on long-term outcomes compared with placebo. In patients with pronounced hyponatremia (<130 mEq/L; n = 92), tolvaptan was associated with reduced cardiovascular morbidity and mortality after discharge (P = .04).

Conclusions: In patients with decompensated heart failure and hyponatremia, standard therapy is associated with less weight loss and dyspnea relief, and unfavorable longer-term outcomes compared to those with normonatremia. Tolvaptan is associated with more favorable in-hospital effects and, possibly, long-term outcomes in patients with severe hyponatremia.

Trial registration: ClinicalTrials.gov NCT00071331.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Antidiuretic Hormone Receptor Antagonists*
  • Arginine Vasopressin / blood
  • Benzazepines / therapeutic use*
  • Diuretics / therapeutic use
  • Dyspnea / drug therapy
  • Dyspnea / etiology
  • Female
  • Furosemide / therapeutic use
  • Heart Failure, Systolic / complications
  • Heart Failure, Systolic / drug therapy*
  • Heart Failure, Systolic / mortality
  • Humans
  • Hyponatremia / complications
  • Hyponatremia / drug therapy*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Tolvaptan
  • Weight Loss / drug effects

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • Diuretics
  • Arginine Vasopressin
  • Tolvaptan
  • Furosemide

Associated data

  • ClinicalTrials.gov/NCT00071331