Hypokalaemia associated with hydrochlorothiazide used in the treatment of hypertension in NHANES 1999–2018

Hydrochlorothiazide is the most common thiazide diuretic used for hypertension in the US. Yet, hypokalaemia is a well-recognised adverse effect. To evaluate the prevalence and factors associated with hypokalaemia (serum potassium < 3.5 mmol/L) among hydrochlorothiazide users, we included US adults aged ≥20 years in the 1999–2018 National Health and Nutrition Examination Survey. Participants were categorised according to the use of hydrochlorothiazide and other antihypertensive agents. Factors associated with hypokalaemia, including demographics and prescription patterns (monotherapy vs single-pill fixed-dose combination vs polytherapy) were studied using multivariable logistic regression. Hypokalaemia was present in 12.6% of the hydrochlorothiazide users, equivalent to ~2.0 million US adults. Women (adjusted OR, 2.22; 95% CI, 1.74–2.83), non-Hispanic blacks (adjusted OR, 1.65; 95% CI, 1.31–2.08), underweight (adjusted OR, 4.33; 95% CI, 1.34–13.95), and participants taking hydrochlorothiazide for five years or more (adjusted OR, 1.47; 95% CI, 1.06–2.04) had a higher risk of hypokalaemia. Compared to monotherapy, fixed-dose combination therapy (adjusted OR, 0.32; 95% CI, 0.21–0.48) was associated with the lowest risk. Among those taking potassium supplements, hypokalaemia was found in 27.2% of participants on monotherapy and 17.9% on polytherapy. The prevalence of hypokalaemia among hydrochlorothiazide users was considerable, even among participants who also took potassium supplements. Women, ethnic minorities, underweight, monotherapy, and participants with long-term therapy are more likely to have hypokalaemia. Regular monitoring of potassium and combination with potassium-sparing drugs are needed.