Efficacy and safety of hydrochlorothiazide versus chlorthalidone in patients with hypertension: a systematic review and meta-analysis

Abstract

Background: Although thiazide diuretics are widely used for treating hypertension (HTN) , the comparative efficacy and safety of hydrochlorothiazide (HCTZ) versus chlorthalidone (CTD) for the management of patients with HTN is not well-established. Materials and Methods: A thorough literature search was conducted across two electronic databases (MEDLINE and Cochrane) from inception through May 2023 to identify randomized controlled trials and/or observational double-arm studies evaluating the effects of HCTZ versus CTD on cardiovascular and safety outcomes in patients with HTN. Evaluations were reported as hazard ratios (HRs) with 95% confidence intervals (CI) and analysis was performed using a random effects model. A P-value<0.05 was considered significant in all cases. Results: From the 409 articles retrieved from initial search, four potentially relevant studies were included in the final analysis. No significant differences were noted for all the cardiovascular outcomes namely MACE, myocardial infarction (MI), stroke, hospitalization for heart failure (HHF), and angina between the HCTZ and CTD arms. However, patients using CTD had significantly higher rates of hypokalemia and hyponatremia when compared with patients using HCTZ. There was no significant difference in the risk of acute kidney injury between the two arms. Conclusion: HCTZ and CTD demonstrated similar efficacy profile with respect to cardiovascular outcomes. However, HCTZ appeared to be safer due to lower risk of electrolyte imbalances like hypokalemia and hyponatremia associated with it when compared with CTD.