Thiazide-related diuretics are recommended as first-line treatment in most hypertension guidelines and have been shown to be especially beneficial in resistant and salt-sensitive forms of hypertension. However, there are variations in the properties of thiazide-related medications and few studies have compared hydrochlorothiazide (HCTZ) with the thiazide-like indapamide (INDAP) and chlorthalidone (CTDN) despite the fact that both INDAP and CTDN have been recommended as a replacement for HCTZ.

A systematic review and meta-analysis of 14 head-to-head randomized controlled trials contrasting two or three of the diuretics HCTZ, CTDN, and INDAP located no trials comparing CTDN with INDAP and all trials lacked cardiovascular events as outcomes. Overall INDAP produced a greater reduction in SBP of (−5.1mmHg, 95% CI, −8.7 to −1.6, P=0.004) compared to HCTZ without greater adverse effects. Limited evidence suggests that CTDN may be even more effective vs. HCTZ (−6.3mmHg, −16.3 to 3.7). With regards to metabolic adverse effects, no detectable differences were noted between HCTZ and INDAP

When evaluating first-line treatment for patients with hypertension, clinicians may also wish to consider CTDN and INDAP; CTDN has only one unscored dose preparation which is the maximum recommended dose (this may not be practical for some patients) while INDAP has low and intermediate dose formulations.

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