Hyponatremia associated with thiazide diuretics is more common than suggested in product labeling, according to a nationwide study from Denmark. Especially in the early months of treatment and in older adults and those with comorbidities, the risk of hyponatremia exceeds 3%, according to the study.
The population and register-based cohort study using target trial emulation of patient experiences from Jan. 1, 2014, through Oct. 31, 2018. People aged 40 years or older who had no recent prescription for any antihypertensive drug, had no previous hyponatremia, and were eligible for the studied antihypertensive treatments were included in 2 emulated trials: a comparison of new use of bendroflumethiazide (BFZ) versus a calcium-channel blocker (CCB) and a comparison of new use of hydrochlorothiazide plus a renin–angiotensin system inhibitor (HCTZ–RASi; that is, combination pill) versus a RASi alone.
Based on 2-year cumulative incidences of sodium levels less than 130 mmol/L using stabilized inverse probability of treatment–weighted survival curves, the investigators found: “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. The 2-year cumulative incidences of hyponatremia were 3.83% for BFZ and 3.51% for HCTZ–RASi. The risk differences were 1.35% (95% 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. The 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.”