Half a Century of Hydrochlorothiazide: Facts, Fads, Fiction, and Follies

Hydrochlorothiazide (HCTZ) has become by far the most commonly prescribed antihypertensive drug in the US. In 2008, 47.8 million prescriptions were written for HCTZ alone and 87.1 million prescriptions for HCTZ combinations. However, there is no evidence that HCTZ in its usual dose of 12.5-25 mg daily reduces myocardial infarction, stroke, or death. In a meta-analysis of 19 randomized trials with over 1400 patients, the 24-hour decrease in blood pressure with HCTZ was inferior to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and calcium channel blockers (P <.001 for all). Even in combination with an angiotensin-converting enzyme inhibitor, HCTZ was found to reduce morbidity and mortality less well than a calcium channel blocker. As measured by the adherence rate, thiazides are less well tolerated than any other drug class. Because outcome data at the usual daily dose of 12.5-25 mg are lacking, antihypertensive efficacy is paltry, and adherence is poor, HCTZ is an inappropriate first-line drug in hypertension. If a “thiazide-type” diuretic is indicated, either chlorthalidone or indapamide should be selected.