Ann Intern Med

Thiazide-induce hyponatremia risk may be greater than what’s suggested by drug labels

December 21, 2023

Initiating treatment with thiazide diuretics may substantially increase hyponatremia risk, particularly during the first months of treatment, and more so than what's currently indicated by drug labeling.

• This population and registry-based cohort study using target trial emulation was conducted in Denmark from January 1, 2014 to October 31, 2018.
• Hyponatremia measurementc consisted of two-year cumulative incidences of sodium levels less than 130 mmol/L using stabilized inverse probability of treatment-weighted survival curves.
• Two target trials were emulated among persons ages >40 who had no recent prescription for any antihypertensive drug and had no previous hyponatremia.
• The first target trial emulation compared new use of bendroflumethiazide (BFZ) vs. a calcium-channel blocker (CCB). The second target trial emulation compared new use of hydrochlorothiazide plus a renin-angiotensin system inhibitor (HCTZ-RASi; that is, combination pill) vs. RASi alone.
• The study compared 37,786 new users of BFZ with 44,963 of a CCB and 11,943 new users of HCTZ-RASi with 85,784 of a RASi.
• Two-year cumulative incidences of hyponatremia were 3.83% for BFZ and 3.51% for HCTZ-RASi. The risk differences were 1.35% (95% confidence interval [CI], 1.04% to 1.66%) between BFZ and CCB and 1.38% (CI, 1.01% to 1.75%) between HCTZ-RASi and RASi; risk differences were higher with older age and higher comorbidity burden.
• Respective hazard ratios were 3.56 (CI, 2.76 to 4.60) and 4.25 (CI, 3.23 to 5.59) during the first 30 days since treatment initiation and 1.26 (CI, 1.09 to 1.46) and 1.29 (CI, 1.05 to 1.58) after 1 year.

Source:

Andersson NW, et al. (2023, December 19). Ann Intern Med. Cumulative Incidence of Thiazide-Induced Hyponatremia: A Population-Based Cohort Study. https://pubmed.ncbi.nlm.nih.gov/38109740/