Risks of Vaptans in Hypernatremia and Serum Sodium Overcorrection: A Systematic Review and Meta‐analysis of Randomised Controlled Trials

Objective Serum sodium overcorrection and hypernatremia are significant health risks. We conducted a systematic review and meta-analysis to evaluate the risks of vaptans in hypernatremia and serum sodium overcorrection. Methods We searched PubMed, Embase, and CENTRAL for randomised controlled trials. We included studies comparing vaptans and placebo with data on hypernatremia and serum sodium overcorrection. The study quality was assessed using the Cochrane Collaboration's risk-of-bias assessment tool. Fixed-effect model meta-analysis was used to pool the data. Different analyses were performed to ensure the accuracy of the results. Results Twenty-eight studies were included in the meta-analysis of hypernatremia incidence. Treatment with vaptans resulted in a higher risk of hypernatremia than placebo (3.8% vs 1.0%, odds ratio [OR] 2.69; 95% confidence interval [CI] 1.97-3.68). The subgroup with baseline hyponatremia had a lower risk of hypernatremia incidence; however, the use of loop diuretics increased the risk. Fourteen studies were included in the analysis of the incidence of serum sodium overcorrection. A higher risk of serum sodium overcorrection was found in using vaptans vs placebo (4.4% vs 1.4%; OR 2.26; 95% CI 1.32-3.86). Conclusion Vaptans showed higher risks in the incidence of hypernatremia and serum sodium overcorrection than placebo. In addition, combination with loop diuretics increased the risk of hypernatremia. The risk of serum sodium overcorrection should be concerned in patients with hyponatremia and normal serum sodium equally. Using a low dose of vaptans can reduce both risks.