Hypertension is the major cardiovascular (CV) risk factor and remains inadequately treated in most populations. Thiazides have been the mainstay of hypertension treatment, either as monotherapy or in combination with other antihypertensives.
The most overwhelming evidences of blood pressure (BP) reduction, CV risk reduction, stroke reduction and mortality reduction are demonstrated with chlorthalidone (CTD), established through many landmark studies including the latest SPRINT trial. Chlorthalidone has a longer elimination half life and is two-times more potent than hydrochlorothiazide (HCTZ). The 24 hours BP control, specially late-night to early-morning control is better with CTD compared to HCTZ.
The American Diabetes Association recommends various drugs including a thiazide diuretic to achieve BP targets. Despite a less favorable metabolic profile, initial therapy with thiazide-like diuretics offers similar, and in some instances possibly superior CV outcomes in older hypertensive adults with metabolic syndrome, as compared to treatment with calcium channel blockers (CCB) and angiotensin converting enzyme inhibitor (ACE-I).
Hypokalemia is the major concern associated with CTD use, probably because of use of high doses > 25 mg. Use of low-dose CTD, especially 6.25 mg, is not associated with any significant change in potassium and sodium levels. This further reduces the risk of new-onset diabetes. Published Indian evidence indicates that use of low-dose of CTD (6.25 mg) could reduce dose-related concerns about metabolic adverse effects.
Thiazide-type diuretics offer added beneficial effects in terms of reduced risk of hip and pelvic fractures in elderly. ALLHAT and SHEP study have demonstrated that development of incident diabetes with CTD did not have significant associations with CV mortality rate or total mortality rate.
In conclusion, the risk of diabetes associated with CTD should not discourage clinicians from using it long-term to reduce CV risks. CV risk reduction remains the ultimate goal of any antihypertensive therapy and the beneficial effects of CTD remain unsurpassed in this aspect.
Keywords: Hypertension, Chlorthalidone, Diuretics, Thiazides.
How to cite this article: Pareek A, Abhyankar M, Ghag S. Renaissance of Chlorthalidone. Hypertens J 2016;2(4):200-208.
Source of support: Nil
Conflict of interest: Authors are employed with IPCA laboratories Ltd. in research work of Chlorthalidone.