Hyponatraemia in acute HF: Tolvaptan effective, but does not reduce mortality

Tolvaptan improves dyspnoea, increases sodium levels and reduces body weight in patients with acute heart failure (HF) with or without hyponatraemia, but no significant effect is seen in mortality or rehospitalization, according to a recent meta-analysis.

“Hyponatraemia is common in patients with HF. Even mild hyponatraemia is associated with increased risks of adverse outcomes, such as mortality,” said Dr Cheuk-Chun Szeto of the Chinese University of Hong Kong. [Clin J Am Soc Nephrol 2015;10:2268-2278]

“Fluid restriction is useful for managing hyponatraemia in HF, with the rule of thumb being a fluid intake that is 500 mL less than the patient’s 24-hour urine volume, but compliance is difficult,” he continued. [Am J Med 2013;126(Suppl 1):S1-S42] 

Nevertheless, both American and European guidelines recommend fluid restriction as first-line treatment for most forms of chronic hyponatraemia. [J Am Soc Nephrol 2017;28:1340-1349]

“Vasopressin receptor antagonists are trendy drugs in hyponatraemia, with tolvaptan being the most commonly used agent,” said Szeto. “While tolvaptan is effective in treatment of acute HF with or without hyponatraemia, a recent meta-analysis of 14 trials showed no effect in reducing mortality or rehospitalization.” [J Int Med Res 2019;47:5414-5425]

In the meta-analysis, tolvaptan was found to significantly reduce body weight (mean change, -1.28 kg), increase serum sodium level (mean change, +3.48 mmol/L), and improve dyspnoea function (odds ratio [OR], 1.43; 95 percent confidence interval [CI], 1.26 to 1.62) vs conventional treatment in patients with acute HF with or without hyponatraemia. However, no significant reduction was seen with tolvaptan in the risk of mortality (OR, 1.12; 95 percent CI, 0.71 to 1.76) or rehospitalization (OR, 1.06; 95 percent CI, 0.94 to 1.21). [J Int Med Res 2019;47:5414-5425]

“Because of the lack of improvement in hard outcomes, European guidelines actually recommend against the use of vasopressin receptor antagonists in chronic hyponatraemia, although American guidelines recommend their use as one of the first-line treatment options,” Szeto pointed out. [J Am Soc Nephrol 2017;28:1340-1349]

“Extracorporeal therapies, commonly used in acute HF with or without hyponatraemia, are useful in patients with fluid overload, but a dialysis component is needed to improve plasma sodium,” he added. [Am J Kidney Dis 2016;68:645-657] “Furosemide results in deficit in urinary concentration and dilution, and can therefore improve hyponatraemia in HF if patients are fluid overloaded, or if urine concentration is much higher than plasma.”