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September 11, 2026Journal of the American College of Cardiology168 citations

Antihypertensive Efficacy of Hydrochlorothiazide as Evaluated by Ambulatory Blood Pressure Monitoring

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FMFranz H. MesserliHMHarikrishna MakaniABAlexandre Benjo

Key Points

  • To evaluate the antihypertensive efficacy of hydrochlorothiazide compared with other drug classes using 24-hour ambulatory blood pressure monitoring.
  • Systematic review of randomized trials identified through Medline, Cochrane, and Embase comparing 24-hour ambulatory blood pressure changes with hydrochlorothiazide against other antihypertensive classes.
  • Identified 14 randomized studies evaluating hydrochlorothiazide at 12.5 to 25 mg (N=1,234) and 5 studies evaluating 50 mg (N=229).
  • Hydrochlorothiazide at 12.5 to 25 mg decreased 24-hour systolic BP by 6.5 mm Hg (95% CI: 5.3 to 7.7) and diastolic BP by 4.5 mm Hg (95% CI: 3.1 to 6.0), demonstrating inferior efficacy compared to ACE inhibitors (12.9/7.7 mm Hg; p < 0.003), ARBs (13.3/7.8 mm Hg; p < 0.001), beta-blockers (11.2/8.5 mm Hg; p < 0.00001), and calcium antagonists (11.0/8.1 mm Hg; p < 0.05).
  • Reductions in 24-hour BP were not significantly different between hydrochlorothiazide 12.5 mg (5.7/3.3 mm Hg) and 25 mg (7.6/5.4 mm Hg; systolic p=0.30, diastolic p=0.15), whereas 50 mg achieved a significantly larger reduction (12.0/5.4 mm Hg) comparable to competitor drug classes.

Abstract

OBJECTIVES: The purpose of this study was to evaluate the antihypertensive efficacy of hydrochlorothiazide (HCTZ) by ambulatory blood pressure (BP) monitoring. BACKGROUND: HCTZ is the most commonly prescribed antihypertensive drug worldwide. More than 97% of all HCTZ prescriptions are for 12.5 to 25 mg per day. The antihypertensive efficacy of HCTZ by ambulatory BP monitoring is less well defined. METHODS: A systematic review was made using Medline, Cochrane, and Embase for all the randomized trials that assessed 24-h BP with HCTZ in comparison with other antihypertensive drugs. RESULTS: Fourteen studies of HCTZ dose 12.5 to 25 mg with 1,234 patients and 5 studies of HCTZ dose 50 mg with 229 patients fulfilled the inclusion criteria. The decrease in 24-h BP with HCTZ dose 12.5 to 25 mg was systolic 6.5 mm Hg (95% confidence interval: 5.3 to 7.7 mm Hg) and diastolic 4.5 mm Hg (95% confidence interval: 3.1 to 6.0 mm Hg) and was inferior compared with the 24-h BP reduction of angiotensin-converting enzyme inhibitors (mean BP reduction 12.9/7.7 mm Hg; p < 0.003), angiotensin-receptor blockers (mean BP reduction 13.3/7.8 mm Hg; p < 0.001), beta-blockers (mean BP reduction 11.2/8.5 mm Hg; p < 0.00001), and calcium antagonists (mean BP reduction 11.0/8.1 mm Hg; p < 0.05). There was no significant difference in both systolic (p = 0.30) and diastolic (p = 0.15) 24-h BP reduction between HCTZ 12.5 mg (5.7/3.3 mm Hg) and HCTZ 25 mg (7.6/5.4 mm Hg). However, with HCTZ 50 mg, the reduction in 24-h BP was significantly higher (12.0/5.4 mm Hg) and was comparable to that of other agents. CONCLUSIONS: The antihypertensive efficacy of HCTZ in its daily dose of 12.5 to 25 mg as measured in head-to-head studies by ambulatory BP measurement is consistently inferior to that of all other drug classes. Because outcome data at this dose are lacking, HCTZ is an inappropriate first-line drug for the treatment of hypertension.

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Cite This Study

Messerli et al. (2011) studied this question.

synapsesocial.com/papers/6aa3731b1ea538cad77b45e8https://doi.org/10.1016/j.jacc.2010.07.053
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