Redefining diuretics use in hypertension: why select a thiazide-like diuretic?

Abstract

: Diuretics are listed in hypertension guidelines as one of three equally weighted first-line treatment options. In order to differentiate between antihypertensives, a lot of discussion has been directed at side effect profiles and as a result, has created a perhaps disproportionate fear of the metabolic effects that can be associated with diuretics. Data, however, show that the risk of a clinically meaningful change in laboratory parameters is very low, whereas the benefits of volume control and natriuresis are high and the reductions in morbidity and mortality are clinically significant. Moreover, as clinically significant differences in safety and efficacy profiles exist among diuretics, several international guidelines have started making a distinction between thiazides (hydrochlorothiazide) and thiazide-like (chlorthalidone, indapamide) diuretics; and some of them now recommend longer acting thiazide-like diuretics. In time, pending more data, chlorthalidone and indapamide may need to be subdivided further into separate classifications.

FIGURE 1

Results of recent meta-analyses that compare therapeutic classes. Results of recent meta-analyses that compare the effect of diuretics on selected clinical endpoints with that of other therapeutic classes [–20]. (a) Stroke and heart failure. (b) Cardiovascular and all-cause mortality. ^∗Not explicitly defined. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; CI, confidence interval; HTN, hypertension; HR, hazard ratio; LD, low dose; ND, no data in publication; PL, placebo; RASI, renin–angiotensin system inhibitor; RR, relative risk; T2D, type 2 diabetes mellitus; TL, thiazide-like diuretic; TZ, thiazide diuretic.

FIGURE 2

Meta-analysis for SBP reduction. (a) Indapamide versus HCTZ. (b) Chlorthalidone versus HCTZ. Adapted with permission from [55]. Studies: Elliott et al.[56], Malini et al.[57], Spence et al.[58], Emeriau et al.[59], Kreeft et al.[60], Madkour et al.[61], Plante et al.[62], Plante et al.[63], Krum et al.[64], Radevski et al.[65], Ernst et al.[51], Kwon et al.[66], Pareek et al.[67]. Differences in means and 95% CI are presented. HCTZ, hydrochlorothiazide; CI, confidence interval.