Published Online
on May 1, 2006

A more recent version of this article appeared on May 9, 2006

This Article Full Text (PDF) Data Supplement All Versions of this Article: 113/18/2201    most recent CIRCULATIONAHA.105.544031v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Davis, B. R. Search for Related Content PubMed PubMed Citation Articles by Davis, B. R. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB AMLODIPINE BESYLATE ATENOLOL CHLORTHALIDONE DOXAZOSIN MESYLATE LISINOPRIL Medline Plus Health Information Blood Pressure Medicines Heart Failure High Blood Pressure Related Collections Other heart failure Congestive Cardiovascular Pharmacology Clinical Studies Related Article

Submitted on February 18, 2005
Revised on February 24, 2006
Accepted on February 24, 2006

Role of Diuretics in the Prevention of Heart Failure. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial

Barry R. Davis MD, PhD^*, Linda B. Piller MD, MPH, Jeffrey A. Cutler MD, MPH, Curt Furberg MD, PhD, Kay Dunn PhD, Stanley Franklin MD, David Goff MD, PhD, Frans Leenen MD, PhD, Syed Mohiuddin MD, Vasilios Papademetriou MD, Michael Proschan PhD, Allan Ellsworth PharmD, John Golden MD, Pedro Colon MD, Richard Crow MD, for the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Collaborative Research Group

From the University of Texas School of Public Health (B.R.D., L.B.P., K.D.), Houston; National, Heart, Lung, and Blood Institute (J.A.C., M.P.), Bethesda, Md; Wake Forest University School of Medicine (C.F., D.G.), Winston-Salem, NC; University of California at Irvine (S.F.), Irvine; University of Ottawa Heart Institute (F.L.), Ottawa, Ontario, Canada; Creighton Cardiac Center (S.M.), Omaha, Neb; Veterans Affairs Medical Center (V.P.), Washington, DC; University of Washington (A.E.), Seattle; Penderbrook Medical Center (J.G.), Fairfax, Va; Centro Cardiovascular de Caguas (P.C.), Caguas, Puerto Rico; and University of Minnesota (R.C.), Minneapolis.

^* To whom correspondence should be addressed. E-mail: barry.r.davis{at}uth.tmc.edu.

Background--Hypertension is a major cause of heart failure (HF) and is antecedent in 91% of cases. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) stipulated assessment of the relative effect of chlorthalidone, lisinopril, and amlodipine in preventing HF.

Methods and Results--ALLHAT was a double-blind, randomized, clinical trial in 33 357 high-risk hypertensive patients aged 55 years. Hospitalized/fatal HF outcomes were examined with proportional-hazards models. Relative risks (95% confidence intervals; P values) of amlodipine or lisinopril versus chlorthalidone were 1.35 (1.21 to 1.50; <0.001) and 1.11 (0.99 to 1.24; 0.09). The proportional hazards assumption of constant relative risk over time was not valid. A more appropriate model showed relative risks of amlodipine or lisinopril versus chlorthalidone during year 1 were 2.22 (1.69 to 2.91; <0.001) and 2.08 (1.58 to 2.74; <0.001), and after year 1, 1.22 (1.08 to 1.38; P=0.001) and 0.96 (0.85 to 1.10; 0.58). There was no significant interaction between prior medication use and treatment. Baseline blood pressures were equivalent (146/84 mm Hg) and at year 1 were 137/79, 139/79, and 140/80 mm Hg in those given chlorthalidone, amlodipine, and lisinopril. At 1 year, use of added open-label atenolol, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers in the treatment groups was similar.

Conclusions--HF risk decreased with chlorthalidone versus amlodipine or lisinopril use during year 1. Subsequently, risk for those individuals taking chlorthalidone versus amlodipine remained decreased but less so, whereas it was equivalent to those given lisinopril. Prior medication use, follow-up blood pressures, and concomitant medications are unlikely to explain most of the HF differences. Diuretics are superior to calcium channel blockers and, at least in the short term, angiotensin-converting enzyme inhibitors in preventing HF in hypertensive individuals.

Key words: heart failure • diuretics • hypertension

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