Role of diuretics in the prevention of heart failure: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
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.


RESULTS
ALLHAT was a double-blind, randomized, clinical trial in 33,357 high-risk hypertensive patients aged > or =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.
Davis
Barry R
BR
The University of Texas School of Public Health, Houston, TX 77030, USA. barry.r.davis@uth.tmc.edu
Piller
Linda B
LB
Cutler
Jeffrey A
JA
Furberg
Curt
C
Dunn
Kay
K
Franklin
Stanley
S
Goff
David
D
Leenen
Frans
F
Mohiuddin
Syed
S
Papademetriou
Vasilios
V
Proschan
Michael
M
Ellsworth
Allan
A
Golden
John
J
Colon
Pedro
P
Crow
Richard
R
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002752:Chlorthalidone / Q000627:therapeutic use*; D004232:Diuretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D017292:Doxazosin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000453:epidemiology / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D015994:Incidence; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control; D016016:Proportional Hazards Models; D012306:Risk; D016896:Treatment Outcome
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; D017311:Amlodipine; D001262:Atenolol; D017706:Lisinopril; D017292:Doxazosin; D002752:Chlorthalidone