Validation of heart failure events in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants assigned to doxazosin and chlorthalidone

Abstract

Background: The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, double-blind, active-controlled trial designed to compare the rate of coronary heart disease events in high-risk hypertensive participants initially randomized to a diuretic (chlorthalidone) versus each of three alternative antihypertensive drugs: alpha-adrenergic blocker (doxazosin), ACE-inhibitor (lisinopril), and calcium-channel blocker (amlodipine). Combined cardiovascular disease risk was significantly increased in the doxazosin arm compared to the chlorthalidone arm (RR 1.25; 95% Cl, 1.17-1.33; P < .001), with a doubling of heart failure (fatal, hospitalized, or non-hospitalized but treated) (RR 2.04; 95% Cl, 1.79-2.32; P < .001). Questions about heart failure diagnostic criteria led to steps to validate these events further. Methods and Results: Baseline characteristics (age, race, sex, blood pressure) did not differ significantly between treatment groups (P