The Choice of Thiazide Diuretics

Abstract

Thiazide diuretics were introduced in the United States for the treatment of hypertension in 1957. The first of these, chlorothiazide, was soon accompanied by a large number of other sulfonamide derivatives, including chlorthalidone. Hydrochlorothiazide (HCTZ) rapidly became the most commonly prescribed antihypertensive drug in the United States, whereas bendroflumethiazide was most popular in the United Kingdom. The initial popularity of HCTZ in the United States was abetted by its use in the first controlled trial of the treatment of nonmalignant hypertension, the Veterans’ Affairs Cooperative Study.1 The starting dose of HCTZ was 50 mg/d, and it was used along with reserpine and hydralazine. A number of other trials published in the 1970s all used higher doses of diuretic, for example, ≥50 mg of HCTZ per day.2 For reasons unknown to me, chlorthalidone was chosen to be the diuretic in the first large controlled trial of the treatment of hypertension, the Hypertension Detection and Follow-Up Program.3 In the Hypertension Detection and Follow-Up Program, all 10 940 patients were started on chlorthalidone from 25 to 100 mg/d. Other drugs were added to achieve control of the blood pressure. In addition, half were assigned to “referred” care and the other half to more closely monitored and intensively treated “stepped” care. The stepped care–treated half achieved a 4.4% further reduction in diastolic blood pressure and a 17.0% reduction …