title: 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% CI, 1.17-1.33; P <.001), with a doubling of heart failure (fatal, hospitalized, or non-hospitalized but treated) (RR 2.04; 95% CI, 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 <.05) for participants with heart failure events. Post-event pharmacologic management was similar in both groups and generally conformed to accepted heart failure therapy. Central review of a small sample of cases showed high adherence to ALLHAT heart failure criteria. Of 105 participants with quantitative ejection fraction measurements provided, (67% by echocardiogram, 31% by catheterization), 29/46 (63%) from the chlorthalidone group and 41/59 (70%) from the doxazosin group were at or below 40%. Two-year heart failure case-fatalities (22% and 19% in the doxazosin and chlorthalidone groups, respectively) were as expected and did not differ significantly (RR 0.96; 95% CI, 0.67-1.38; P = 0.83). CONCLUSION: Results of the validation process supported findings of increased heart failure in the ALLHAT doxazosin treatment arm compared to the chlorthalidone treatment arm.
authors.affiliation: The University of Texas School of Public Health, Houston, TX, USA. lpiller@sph.uth.tmc.edu
authors.forename: Linda B
authors.initials: LB
authors.lastname: Piller
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Cutler
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.forename: Jackson T
authors.initials: JT
authors.lastname: Wright
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Williamson
authors.forename: Frans HH
authors.initials: FH
authors.lastname: Leenen
authors.forename: Paula T
authors.initials: PT
authors.lastname: Einhorn
authors.forename: Otelio S
authors.initials: OS
authors.lastname: Randall
authors.forename: John S
authors.initials: JS
authors.lastname: Golden
authors.forename: L Julian
authors.initials: LJ
authors.lastname: Haywood