Chlorthalidone versus hydrochlorothiazide: a tale of tortoises and a hare.

See related article, pp 1001–1007 Chlorthalidone (CTD) is the best diuretic for the treatment of hypertension, both in blood pressure–lowering efficacy and, most importantly, in prevention of hypertension-related morbidity and mortality. Despite this fact, hydrochlorothiazide (HCTZ) has been and continues to be by far the most frequently prescribed diuretic in the United States.1 Even among patients with resistant hypertension, where a more potent diuretic is especially needed, CTD is chosen in only 3% of patients.2 There are numerous possible reasons for this flagrant failure of evidence-based medicine. I will refer to the Aesop tale of “The Tortoise and the Hare” as my way of explaining the paradox. In this reference, physicians are the tortoises, whereas a pharmaceutical company is the hare; here, unlike in the original, the hare easily wins the race. The 2 diuretics were approved for the treatment of hypertension within a year of each other, HCTZ in 1959 and CTD in 1960. Soon thereafter, small trials documented the equal efficacy of CTD in much smaller doses in lowering blood pressure compared with HCTZ3 or other thiazides.4 A few years later, the Multiple Risk Factor Intervention Trial (MRFIT) was begun, and the designers offered the 15 participating clinics the choice of using either HCTZ or CTD; 9 chose HCTZ and 6 chose …