HCTZ and CTD have comparable cardiovascular efficacy, but HCTZ is safer with lower rates of hypokalemia and hyponatremia compared to CTD.
Does hydrochlorothiazide reduce cardiovascular events or improve safety compared to chlorthalidone in patients with hypertension?
Hydrochlorothiazide and chlorthalidone provide comparable cardiovascular protection in patients with hypertension, but hydrochlorothiazide is associated with a lower risk of electrolyte imbalances.
Background Thiazide diuretics are commonly prescribed for the treatment of hypertension (HTN). However, the comparative efficacy and safety of hydrochlorothiazide (HCTZ) versus chlorthalidone (CTD) in managing patients with HTN remain unclear. Materials and Methods A comprehensive literature search was performed using two electronic databases, MEDLINE and Cochrane, from their inception through November 2024. The aim was to identify randomized controlled trials or observational double-arm studies assessing the effects of HCTZ versus CTD on cardiovascular outcomes and safety in patients with HTN. Outcomes were reported as hazard ratios (HRs) with 95% confidence intervals (CIs), and analyses were conducted using a random effects model. A P -value of <0.05 was considered statistically significant. Results Of the 409 articles identified in the initial search, six relevant studies were included in the final analysis. No significant differences were observed between the HCTZ and CTD arms for cardiovascular outcomes, including major adverse cardiovascular events, myocardial infarction, stroke, hospitalization for heart failure, and angina. However, patients receiving CTD experienced significantly higher rates of hypokalemia and hyponatremia compared to those on HCTZ. The risk of acute kidney injury did not differ significantly between the two groups. Conclusion HCTZ and CTD showed comparable efficacy in terms of cardiovascular outcomes. Nevertheless, HCTZ appeared to have a safer profile, with a lower incidence of electrolyte imbalances, such as hypokalemia and hyponatremia, compared to CTD.
Ashraf et al. (2026) studied this question. HCTZ and CTD have comparable cardiovascular efficacy, but HCTZ is safer with lower rates of hypokalemia and hyponatremia compared to CTD.