Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects

source extracted confidence: high 2026-04-09
#blood-pressure #chlorthalidone #diuretics #humans #hydrochlorothiazide

Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects

Roush et al., 2015 | Hypertension | Meta Analysis

Citation

Roush George C, Ernst Michael E, ... Sica Domenic A. Head-to-head comparisons of hydrochlorothiazide with indapamide and chlorthalidone: antihypertensive and metabolic effects. Hypertension. 2015-May;65(5):1041-6. doi:10.1161/HYPERTENSIONAHA.114.05021

Abstract

Hydrochlorothiazide (HCTZ) has often been contrasted with chlorthalidone, but relatively little is known about HCTZ versus indapamide (INDAP). This systematic review retrieved 9765 publications, and from these, it identified 14 randomized trials with 883 patients comparing HCTZ with INDAP and chlorthalidone on antihypertensive potency or metabolic effects. To make fair comparisons, the dose of the diuretic in each arm was assigned 1 of 3 dose levels. In random effects meta-analysis, INDAP and chlorthalidone lowered systolic blood pressure more than HCTZ: -5.1 mm Hg (95% confidence interval, -8.7 to -1.6); P=0.004 and -3.6 mm Hg (95% confidence interval, -7.3 to 0.0); P=0.052, respectively. For both comparisons, there was minimal heterogeneity in effect across trials and no evidence for publication bias. The HCTZ-INDAP contrast was biased in favor of greater HCTZ potency because of a much greater contribution to the overall effect from trials in which the HCTZ arm had a higher dose level than the INDAP arm. For the HCTZ-INDAP comparison, no single trial was responsible for the overall result nor was it possible to detect significant modifications of this comparison by duration of follow-up, high- versus low-bias trials, or the presence or absence of background medications. There were no detectable differences between HCTZ and INDAP in metabolic adverse effects, including effects on serum potassium. In conclusion, these head-to-head comparisons demonstrate that, like chlorthalidone, INDAP is more potent than HCTZ at commonly prescribed doses without evidence for greater adverse metabolic effects.

Key Findings

In conclusion, these head-to-head comparisons demonstrate that, like chlorthalidone, INDAP is more potent than HCTZ at commonly prescribed doses without evidence for greater adverse metabolic effects.

Outcomes Measured

  • blood pressure
  • systolic blood pressure

Population

Field Value
Population See abstract
Sample Size 883
Age Range See abstract
Condition blood pressure

MeSH Terms

  • Blood Pressure
  • Chlorthalidone
  • Diuretics
  • Humans
  • Hydrochlorothiazide
  • Hypertension
  • Hypokalemia
  • Indapamide
  • Potassium
  • Treatment Outcome

Evidence Classification

  • Level: Meta Analysis
  • Publication Types: Journal Article, Meta-Analysis, Systematic Review
  • Vertical: potassium

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09