Annals of Internal MedicineCumulative Incidence of Thiazide-Induced Hyponatremia

Thiazide Diuretics Linked to Increased Hyponatremia Risk

A recent study conducted in Denmark has provided new insights into the risk of hyponatremia associated with thiazide diuretics. This study is critical for understanding the potential risks involved with these commonly prescribed antihypertensive drugs.

Study Design:

• Location and Duration: Conducted in Denmark from January 1, 2014, to October 31, 2018.
• Participants: Adults aged 40 or older, no recent antihypertensive drug prescription, no prior hyponatremia.
• Comparisons: Bendroflumethiazide (BFZ) vs. Calcium-channel blocker (CCB); Hydrochlorothiazide plus renin–angiotensin system inhibitor (HCTZ–RASi) vs. RASi alone.
• Measurements: Two-year cumulative incidences of sodium levels below 130 mmol/L.

Key Findings:

• Incidence Rates: 3.83% for BFZ users and 3.51% for HCTZ–RASi users.
• Risk Differences: 1.35% between BFZ and CCB, 1.38% between HCTZ–RASi and RASi.
• Hazard Ratios: 3.56 in the first 30 days for BFZ, 4.25 for HCTZ–RASi; 1.26 and 1.29 respectively after one year.
• Age and Comorbidity: Higher risk with older age and higher comorbidity burden.
• Limitation: Study assumes prescription filling equals drug use; potential for residual confounding.

HCN Medical Memo
Thiazide diuretics can cause hyponatremia within two weeks of initiation, especially in older patients. This condition is often serious and may lead to life-threatening complications. Up to 10% of hospitalized patients may experience hyponatremia, with thiazides being a common cause​.

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