Antihypertensive Efficacy of Hydrochlorothiazide as Evaluated by Ambulatory Blood Pressure Monitoring: A Meta-Analysis of Randomized Trials

Study Questions:

What is the antihypertensive efficacy of hydrochlorothiazide (HCTZ), as measured by ambulatory blood pressure (BP) monitoring?


A systematic review was made using MEDLINE, Cochrane, and Embase for all the randomized trials that assessed 24-hour BP with HCTZ in comparison with other antihypertensive drugs. Fourteen studies of HCTZ dose 12.5-25 mg with 1,234 patients and five studies of HCTZ dose 50 mg with 229 patients fulfilled the inclusion criteria.


The decrease in 24-hour BP with HCTZ dose 12.5-25 mg was systolic 6.5 mm Hg (95% confidence interval [CI], 5.3-7.7) and diastolic 4.5 mm Hg (95% CI, 3.1-6.0), and was inferior compared with the 24-hour BP reduction of angiotensin-converting enzyme inhibitors (ACEi) (mean BP reduction 12.9/7.7 mm Hg; p < 0.003), angiotensin-receptor blockers (ARBs) (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-hour 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-hour BP was significantly higher (12.0/5.4 mm Hg) and was comparable to that of other agents.


The antihypertensive efficacy of HCTZ in its daily dose of 12.5-25 mg, as measured 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.


Based upon many randomized trials, regardless of age, gender, and race, HCTZ and beta-blockers are no longer considered appropriate first-line drugs for the treatment of hypertension. ACEi, ARBs, and calcium channel blockers alone, or ACEi or ARB in combination with calcium channel blockers, appear to be the drugs of first choice.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Statins, Hypertension

Keywords: Angiotensin Receptor Antagonists, Blood Pressure Monitoring, Ambulatory, Blood Pressure, Hydrochlorothiazide, Confidence Intervals, Diastole, Hypertension, Systole, Calcium Channel Blockers

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