Association between newly initiated thiazide diuretics and hospitalization due to hyponatremia

Purpose Thiazide diuretics are the most common origin of drug-induced hyponatremia. However, population-based studies on clinical outcomes are lacking. We therefore explored the time course and absolute risk of thiazide-associated hospitalization due to hyponatremia in Sweden. Methods Population-based case-control study including patients hospitalized with a principal diagnosis of hyponatremia (n = 11,213) compared with controls (n = 44,801). Linkage of registers was used to acquire data. Multivariable regression was applied to explore time-dependent associations between thiazide diuretics and hospitalization due to hyponatremia. Attributable risks were calculated assessing the disease burden attributable to thiazides. Results Individuals initiating thiazide treatment were exposed to an immediate increase in risk for hospitalization with adjusted odds ratio (aOR) (95% CI) of 48 (28-89). The associations gradually declined reaching an aOR of 2.9 (2.7-3.1) for individuals treated for longer than 13 weeks. The attributable risk of hyponatremia-associated hospitalization due to thiazides of any treatment length was 27% (3095/11,213). Among 806 patients initiating treatment < 90 days before hospitalization, hyponatremia could be attributed to thiazides in 754. Based on nationwide data, 616,678 individuals were initiated on thiazides during the 8-year study period suggesting an absolute risk of 0.12% (754/661,678) for subsequent hospitalization with a main diagnosis of hyponatremia. Conclusions Thiazide diuretics attributed to more than one in four individuals hospitalized due to hyponatremia. The risk increase was very pronounced during the first month of treatment and then gradually declined, without returning to normal. However, the absolute risk for the development of hyponatremia demanding hospitalization may for most individuals be modest.

Automated summary

Thiazide diuretics are the most common cause of drug-induced hyponatremia. This study in Sweden found that individuals initiating thiazide treatment faced an immediate increase in risk for hospitalization due to hyponatremia, which gradually declined over time. However, thiazides were still attributed to more than one in four individuals hospitalized for hyponatremia, with an absolute risk for subsequent hospitalization being modest for most individuals.