Not Just Chlorthalidone: Evidence-Based, Single Tablet, Diuretic Alternatives to Hydrochlorothiazide for Hypertension

Accounting for 15 % of deaths worldwide, hypertension is often treated with hydrochlorothiazide (HCTZ) (50 million prescriptions annually). HCTZ has a <24-h duration of action, is less potent than chlorthalidone and all major antihypertensive drug classes, and is inferior to four antihypertensive drugs for cardiovascular event (CVE) reduction. If there were alternative diuretics, why prescribe HCTZ? Chlorthalidone is often offered as an alternative to HCTZ, but has limited pharmaceutical formulations. However, there are seven evidence-based, single-tablet, alternative diuretics. For reducing CVE, the following are superior to their comparators: chlorthalidone versus four antihypertensives in multiple hypertensive populations; indapamide versus placebo in elderly Chinese (and versus enalapril for left ventricular hypertrophy), triamterene–HCTZ versus placebo in elderly Europeans, amiloride–HCTZ versus three antihypertensives, and indapamide–perindopril versus placebo in three populations. Additionally, chlorthalidone–azilsartan and spironolactone–HCTZ are potent combinations The aldosterone antagonist component of the latter combination has been shown to reduce total mortality by 30 % in heart failure. Five of these seven have multiple dose formulations. Six cost $4–$77 monthly. In conclusion, based on both scientific and practical grounds, new prescriptions for HCTZ are rarely justified.