Efficacy & safety of chlorthalidone vs. hydrochlorothiazide in hypertension: A systematic review & meta-analysis

Background & objectives Diuretics are among the most cost-effective therapies for hypertension, yet uncertainty remains regarding the comparative efficacy and safety of chlorthalidone versus hydrochlorothiazide. Methods A search was conducted in PubMed, Cochrane, Scopus, and Embase. RCTs involving hypertensive patients were included, with chlorthalidone as the intervention and hydrochlorothiazide as the comparator. Risk of bias was assessed using the ROB 2 tool. The mean difference (MD) and relative risk (RR) were used as summary estimates. Safety outcomes were assessed by pooling the incidence of hypokalaemia, using RR. Results Ten RCTs (n = 1,182) were included. Chlorthalidone achieved greater reductions in 24-h ambulatory systolic blood pressure (BP)[MD: -4.21 mmHg, 95% confidence interval (CI): -4.73 to -4.05] and diastolic BP (MD: -2.23 mmHg, 95% CI: -3.13 to -1.32; both P< 0.01). Office systolic BP was also lower with chlorthalidone (MD: -4.10 mmHg, 95% CI -6.11 to -2.08; P< 0.01), whereas office diastolic BP showed no significant difference (MD: -1.70 mmHg, 95% CI -3.40 to 0; P= 0.05). The risk of hypokalaemia did not differ significantly (RR: 1.51, 95% CI 0.83-2.72; P= 0.17). Hypokalaemia was numerically more frequent with chlorthalidone. Interpretation & conclusions Chlorthalidone lowers systolic and diastolic BP more effectively than hydrochlorothiazide without significantly increasing the risk of hypokalaemia. These findings support chlorthalidone as the more efficacious thiazide option, particularly where cost-effective BP control is critical. Larger, long-term RCTs are needed to determine whether these BP benefits translate into superior cardiovascular outcomes.