ALLHAT, or the Soft Science of the Secondary End Point

The recent Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed that the primary end point, coronary heart disease, was identical in the chlorthalidone, lisinopril, and amlodipine groups. Yet the major conclusion of this trial was that thiazide diuretics are superior in preventing 1 or more major forms of cardiovascular disease and should be preferred for first-line antihypertensive therapy. This conclusion was based solely on an analysis of secondary end points and cost. As evidenced by the dictum to "use thiazides for most patients with uncomplicated hypertension" in the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, this interpretation of ALLHAT broadly adumbrated these guidelines. Although diuretics will rightfully remain a cornerstone in antihypertensive therapy, we should remember (as we were told by the ALLHAT investigators) that secondary end points are "soft data" that should not form a basis for main conclusions or lead to a labeling of a drug class as preferred.