Risk of Hyponatremia associated with use of Thiazide Diuretics higher than anticipated

A recent study by Niklas Worm Andersson and team found that the treatment initiation with thiazide diuretics increases the potential risk for hyponatremia, particularly during the initial months of treatment. Based on a population and register-based cohort, the findings were published in the Annals of Internal Medicine.

Thiazide-induced hyponatremia is a condition characterized by low levels of sodium. This is an elusive concern as the existing drug labels suggest it to be rare, occurring at rate less than 1 in 10,000.

This study was conducted in Denmark from January 2014 to October 2018 which aimed to estimate the cumulative incidence of hyponatremia. The research focused on individuals aged 40 years or older with no recent prescription for antihypertensive drugs and no previous hyponatremia. Th research team compared the new use of bendroflumethiazide (BFZ) with a calcium-channel blocker (CCB) and the new use of hydrochlorothiazide plus a renin–angiotensin system inhibitor (HCTZ–RASi) with RASi alone.

Among the 37,786 BFZ users, the outcomes of this study highlighted that the 2-year cumulative incidence of hyponatremia was 3.83% when compared to 3.51% for HCTZ–RASi. The risk differences of 1.35% was found between BFZ and CCB and 1.38% between HCTZ–RASi and RASi respectively. Also, the hazard ratios of the BFZ was 3.56 and HCTZ–RASi was 4.25 in the first 30 days. The study highlighted the outcome of increased substantial risk during the initial months of diuretics treatment.

The implications of the study challenges the existing understanding of the safety profile of thiazide diuretics specially regarding hyponatremia. The excess risk identified were particularly in the early stages of treatment that calls for a reevaluation of prescribing practices and heightened awareness among healthcare providers.

Source:

Andersson, N. W., Wohlfahrt, J., Feenstra, B., Hviid, A., Melbye, M., & Lund, M. (2023). Cumulative Incidence of Thiazide-Induced Hyponatremia. In Annals of Internal Medicine. American College of Physicians. https://doi.org/10.7326/m23-1989