Letter - Diuretics in primary hypertension - Reloaded.

Dear Dr. Mishra,

I agree with you that, diuretics are a gold standard in the treatment of hypertension. Increasingly the guidelines are also recognizing the importance of diuretics, especially in uncomplicated hypertension. This is because of the robust data which diuretics have in their favour, for e.g. HYVET trial with Indapamide which showed a 39% reduction in the rate of death from stroke (P = 0.05), and a 64% reduction in the rate of heart failure (P < 0.001), ALLHAT trial also showed chlorthalidone was superior to lisinopril in lowering BP & preventing aggregate CV events. Hence, we do need to differentiate between Thiazide & Thiazide-like diuretics. A recent meta-analysis states that “Hydrochlorothiazide has often been compared with chlorthalidone, but relatively little is known about Hydrochlorothiazide versus indapamide. This systematic review retrieved 9765 publications, and from these, it identified 14 randomized trials comparing Hydrochlorothiazide with indapamide and chlorthalidone on antihypertensive potency or metabolic effects. Compared with an estimated 9.5 mm Hg reduction in SBP from Hydrochlorothiazide relative to placebo from Peterzan et al., indapamide and chlorthalidone lowered SBP by 54% and 38% more than Hydrochlorothiazide, respectively.

However, there is a general perception, that these diuretics can cause metabolic imbalances. This is especially true for thiazide diuretics at higher dose. But thiazide-like diuretics can also cause some metabolic imbalance, in ALLHAT trial chlorthalidone increased the risk of new-onset diabetes by 43% as compared to lisinopril. In the Trial of Antihypertensive Interventions and Management (TAIM) study, erection-related problems worsened in 28% of men receiving chlorthalidone, this can be a cause of concern as Indian patients are not very comfortable sexual dysfunction with anyone. Though these side-effects are documented with high dose of chlorthalidone and low-dose therapy may minimize the risk of these side effects. However it doesn’t appear to be a class effect as Indapamide, a thiazide type diuretic has been found to be metabolically neutral at a dose of 1.5 mg sustained release or 2.5 mg immediate release.

To conclude, diuretics will remain the mainstay of treatment of uncomplicated HT, especially thiazide-like diuretics as they have wealth of evidences. To maximize benefits, both in terms of BP reduction efficacy & life-saving benefits they should be used at dose used in major clinical trials (12.5–25 mg/day of chlorthalidone used in ALLHAT, or 1.5 mg of indapamide SR used in HYVET).