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.

Evening dosing of antihypertensive therapy to reduce cardiovascular events: a third type of evidence based on a systematic review and meta-analysis of randomized trials.

Nighttime blood pressure strongly predicts cardiovascular events (CVEs). Further, a preliminary trial has shown decreased CVEs from evening vs morning dosing of antihypertensive therapy. Is there additional evidence for evening dosing? The authors systematically classified all hypertension trials as evening dosing trials (EDTs) or usual dosing trials (UDTs).

Chlorthalidone: mechanisms of action and effect on cardiovascular events.

How chlorthalidone (CTDN) reduces risk for cardiovascular events (CVEs) can be considered in light of its ability to lower blood pressure (BP) and its non-BP related, pleiotropic effects. The mechanism by which CTDN lowers BP is unclear but may include alterations in whole body regulation and vasodilatory actions on vasculature, possibly mediated via its inhibitory effects on carbonic anhydrase. Additionally, CTDN has potentially beneficial, non-BP related, pleiotropic effects that include improvements in endothelial function, anti-platelet activity, and oxidative status.