Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure

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.