Superior antihypertensive and cardioprotective effects of chlorthalidone compared with hydrochlorothiazide

Diuretics are the most commonly used drugs for the treatment of hypertension, either alone or in combination with other antihypertensive drugs. Of all diuretics, hydrochlorothiazide (HCTZ) and chlorthalidone (CTD) are the most commonly used, with HCTZ being the most widely prescribed diuretic. Recent studies have shown that CTD is a better diuretic with superior antihypertensive effectiveness and cardiovascular protection. Although these diuretics are chemically, pharmacokinetically and pharmacodynamically different, CTD continues to be called a "thiazide-like" diuretic. The only common features they both share are a sulfhydryl group in their molecules and their common mechanism and site of diuretic action. In order to get a better understanding of the true pharmacologic actions as well as the benefits and risks of these diuretics, a MEDLINE search of the English language literature between 1964 and January 2021 was conducted, using the terms "diuretics", "hydrochlorothiazide", "chlorthalidone", "hypertension", "cardiovascular disease" and "treatment". From this search, 28 pertinent papers were selected and they will be discussed in this review together with collateral literature. The analysis of results revealed that CTD is superior to HCTZ in antihypertensive effectiveness and cardioprotection and should be the preferred diuretic for the treatment of hypertension.