Indapamide: is it the better diuretic for hypertension?

A ttention must be paid to the article by Roush et al 1 in this edition of Hypertension. The authors use robust statistics to compare the antihypertensive potency and adverse effects of hydrochlorothiazide versus indapamide in the 10 publications that could be identified, wherein the 2 drugs were compared head-to-head in trials lasting ≥4 weeks. Indapamide, used as 2.5 mg tablets in all but 1 trial, provided a 54% greater reduction in systolic blood pressure, that is, −5.1 mm Hg (confidence interval, −8.7 to −1.6) than seen with hydrochlorothiazide in doses from 12.5 to 50 mg/d. The relative doses were greater for hydrochlorothiazide in 5 trials and equivalent in 3 trials. The blood pressures were measured by office sphygmo-manometry in all these trials but reference is given to studies using 24-hour ambulatory measurements, which showed ≥24-hour duration of diuretic and antihypertensive efficacy with the immediate formulation of indapamide and ≥32-hour duration with the sustained formulation (which was used in only one of the trials). 2 Roush et al 1 refer to multiple additional vasodilatory actions described in the literature in support of the greater reduction of blood pressure and the longer duration of action of indapamide, well beyond the 12-to 16-hour duration of action of hydrochlorothiazide. The first 2 authors of this article have been involved in studies documenting a longer and stronger antihypertensive effect of chlorthalidone over hydrochlorothiazide, studies that were published as far back as 2004 3 and reiterated in the current article with data from 3 head-to-head comparisons. 1 No such comparisons between chlorthalidone and inda-pamide could be found. Both probably provide full 24-hour antihypertensive efficacy so the choice between them must be based on known additional characteristics of the 2 drugs. There are at ≥3 features which could influence the choice and all 3 favor indapamide over chlorthalidone. These are (1) Ease of use: In the US, generic chlorthalidone is only available as a 25 mg tablet. To approximate the most frequently used 12.5 mg dose of hydrochlorothiazide, the chlorthalidone tablet must be cut in half. Generic indapamide, both in the immediate and delayed action formulations, is available as 1.5, 2.5, and 5 mg tablets so no such manipulation is needed. (2) Cost: The cost of many drugs is higher in United States than in other countries , adding to the markedly higher spending on healthcare in the United States than in countries with a national …