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February 2, 2026The Indian Journal of Medical Research1 citationsOpen Access

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

PAPravesh AggarwalRORanu OzaHSHitendrapal Solanki

Key Result

The provided text is a PRISMA checklist and contains no clinical results regarding the efficacy of chlorthalidone versus hydrochlorothiazide.

Key Points

  • To assess the comparative efficacy and safety of chlorthalidone versus hydrochlorothiazide in treating hypertension.
  • Conducted a systematic review and meta-analysis using databases like PubMed and Cochrane.
  • Included randomized controlled trials (RCTs) involving hypertensive patients.
  • Evaluated blood pressure reductions and incidence of hypokalaemia as safety outcomes.
  • Utilized mean difference (MD) and relative risk (RR) for summary estimates.
  • Chlorthalidone reduced 24-h ambulatory systolic blood pressure by 4.21 mmHg compared to hydrochlorothiazide (P < 0.01).
  • Office systolic blood pressure was lower with chlorthalidone by 4.10 mmHg (P < 0.01).
  • No significant difference in office diastolic blood pressure was found (MD: -1.70 mmHg, P = 0.05).
  • Risk of hypokalaemia was not significantly different (RR: 1.51, P = 0.17), although it appeared more frequent with chlorthalidone.

Study Design

Type

Meta-Analysis

Structured PICO

Does chlorthalidone reduce blood pressure more effectively than hydrochlorothiazide in patients with hypertension?

P
Population
1,182 hypertensive patients pooled from 10 RCTs
I
Intervention
Chlorthalidone alone or in combination therapy
C
Comparator
Hydrochlorothiazide alone or in combination with the same background therapy as the intervention group
O
Outcome
24-h ambulatory (systolic and diastolic) blood pressure changessurrogate

Chlorthalidone lowers systolic and diastolic blood pressure more effectively than hydrochlorothiazide without significantly increasing the risk of hypokalaemia, supporting its use as the more efficacious thiazide option.

Limitations

  • Small number of head-to-head randomised controlled trials assessing cardiovascular outcomes
  • Limited ambulatory blood pressure monitoring-based trials
  • Inclusion of studies using combination therapy, which could confound blood pressure and safety effects

Abstract

Background 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.

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Cite This Study

Aggarwal et al. (2026) conducted a meta-analysis in hypertension. chlorthalidone vs. hydrochlorothiazide was evaluated. The provided text is a PRISMA checklist and contains no clinical results regarding the efficacy of chlorthalidone versus hydrochlorothiazide.

synapsesocial.com/papers/6980fff5c1c9540dea812da7https://doi.org/10.25259/ijmr_1553_2025
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 12020 International Society of Hypertension Global Hypertension Practice Guidelines2020 · 4,219 citations
  2. 2Efficacy of Low-Dose Chlorthalidone and Hydrochlorothiazide as Assessed by 24-h Ambulatory Blood Pressure Monitoring2016 · 96 citations
  3. 3Comparison of Five Antihypertensive Monotherapies and Placebo for Change in Left Ventricular Mass in Patients Receiving Nutritional-Hygienic Therapy in the Treatment of Mild Hypertension Study (TOMHS)1995 · 327 citations
  4. 4A comparison of the antihypertensive effect of chlorthalidone and hydrochlorthiazide1964 · 24 citations
  5. 5Interindividual differences in chlorthalidone concentration in plasma and red cells of man after single and multiple doses1976 · 37 citations