Comparative Antihypertensive Effects of Hydrochlorothiazide and Chlorthalidone on Ambulatory and Office Blood Pressure

Hypertension. 2006 Mar;47(3):352-8. doi: 10.1161/01.HYP.0000203309.07140.d3. Epub 2006 Jan 23.


Low-dose thiazide-type diuretics are recommended as initial therapy for most hypertensive patients. Chlorthalidone has significantly reduced stroke and cardiovascular end points in several landmark trials; however, hydrochlorothiazide remains favored in practice. Most clinicians assume that the drugs are interchangeable, but their antihypertensive effects at lower doses have not been directly compared. We conducted a randomized, single-blinded, 8-week active treatment, crossover study comparing chlorthalidone 12.5 mg/day (force-titrated to 25 mg/day) and hydrochlorothiazide 25 mg/day (force-titrated to 50 mg/day) in untreated hypertensive patients. The main outcome, 24-hour ambulatory blood pressure (BP) monitoring, was assessed at baseline and week 8, along with standard office BP readings every 2 weeks. Thirty patients completed the first active treatment period, whereas 24 patients completed both. An order-drug-time interaction was observed with chlorthalidone; therefore, data from only the first active treatment period was considered. Week 8 ambulatory BPs indicated a greater reduction from baseline in systolic BP with chlorthalidone 25 mg/day compared with hydrochlorothiazide 50 mg/day (24-hour mean = -12.4+/-1.8 mm Hg versus -7.4+/-1.7 mm Hg; P=0.054; nighttime mean = -13.5+/-1.9 mm Hg versus -6.4+/-1.8 mm Hg; P=0.009). Office systolic BP reduction was lower at week 2 for chlorthalidone 12.5 mg/day versus hydrochlorothiazide 25 mg/day (-15.7+/-2.2 mm Hg versus -4.5+/-2.1 mm Hg; P=0.001); however, by week 8, reductions were statistically similar (-17.1+/-3.7 versus -10.8+/-3.5; P=0.84). Within recommended doses, chlorthalidone is more effective in lowering systolic BPs than hydrochlorothiazide, as evidenced by 24-hour ambulatory BPs. These differences were not apparent with office BP measurements.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Pressure / drug effects*
  • Blood Pressure Determination / methods*
  • Blood Pressure Monitoring, Ambulatory
  • Chlorthalidone / administration & dosage
  • Chlorthalidone / adverse effects
  • Chlorthalidone / therapeutic use*
  • Cross-Over Studies
  • Drug Administration Schedule
  • Drug Interactions
  • Female
  • Humans
  • Hydrochlorothiazide / administration & dosage
  • Hydrochlorothiazide / adverse effects
  • Hydrochlorothiazide / therapeutic use*
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Office Visits
  • Single-Blind Method
  • Sodium Chloride Symporter Inhibitors / administration & dosage
  • Sodium Chloride Symporter Inhibitors / adverse effects
  • Sodium Chloride Symporter Inhibitors / therapeutic use*
  • Time Factors


  • Sodium Chloride Symporter Inhibitors
  • Hydrochlorothiazide
  • Chlorthalidone