Which diuretic is the preferred agent for treating essential hypertension: hydrochlorothiazide or chlorthalidone?

Since their introduction over 50 years ago thiazide and thiazide-like diuretics have been a mainstay in the treatment of hypertension. Yet despite outcome evidence with chlorthalidone, the preponderance of usage has been with hydrochlorothiazide-either as monotherapy or in combination with other drugs. There is an increasing debate as to whether or not there are significant differences between hydrochlorothiazide and chlorthalidone. Early outcome studies, upon which the recommendations were made, utilized higher doses than those not only commonly employed in clinical practice, but also studied in more recent outcome trials. In addition, data suggests that chlorthalidone may be more potent, in equal doses, in its BP response than hydrochlorothiazide. A fundamental question asked in the debate is whether or not the benefits attributed to chlorthalidone as a thiazide-like diuretic may be reasonably ascribed to thiazides given differences in their pharmacokinetic properties and perhaps some other more recently noted differences.