Thiazide-associated hyponatremia in arterial hypertension patients: A nationwide population-based cohort study

Objective

Thiazides are the first-line treatment for hypertension, however, they have been associated with hospitalizations for thiazide-associated hyponatremia (TAH). The aim of this study was to evaluate the risk of TAH and other drug-associated hyponatremia in a Korean population.

Methods

The study used big data from the National Health Insurance Sharing Service of 1,943,345 adults treated for hypertension from January 2014 to December 2016. The participants were divided into two groups based on the use of thiazides. Cox proportional hazard models were used to identify independent risk factors for the occurrence of hyponatremia.

Results

The study found that hyponatremia-related hospitalizations were significantly higher in the thiazide group than the control group (2.19% vs. 1.45%). The risk increased further with concurrent use of other diuretics or desmopressin, and thiazide+spironolactone+desmopressin and hospitalization risk further increased (4.0 and 6.9 times). Multivariate analysis showed that hyponatremia occurrence increased with age, diabetes mellitus, depression, and thiazide use (hazard ratio = 1.436, p < 0.001). The thiazide group had better 6-year overall survival than the control group but had more fractures and hyponatremia.

Conclusions

Thiazide use is associated with an increased risk of hyponatremia and related complications. However, the mortality rate decreased in those who received thiazides, suggesting that thiazide use itself is not harmful and may help decrease complications and improve prognosis with proper, cautious use in high-risk patients.