The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Heart Failure Validation Study: diagnosis and prognosis.
BACKGROUND
ALLHAT, a randomized, double-blind, active-controlled hypertension treatment trial in 42,418 patients, reported that a thiazide-type diuretic (chlorthalidone) was superior to a calcium channel blocker (amlodipine), an angiotensin-converting enzyme inhibitor (lisinopril), and an alpha1-blocker (doxazosin) in preventing the new onset of heart failure (HF). However, questions have been raised regarding the validity of the HF diagnosis.


METHODS
The ALLHAT HF Validation Study was designed to validate and elucidate the significance of HF events in ALLHAT. Records for 2778 HF hospitalizations in 1935 patients were centrally reviewed using several prespecified algorithms (based on ALLHAT and Framingham criteria) and reviewers' global clinical judgment. Percent agreement with diagnoses assigned by ALLHAT site physicians, relative risks across randomized comparisons, incidence rates, and mortality after HF hospitalization were evaluated for first events validated by each of the criteria sets.


RESULTS
Percent agreements with site physician diagnoses were 71%, 80%, and 84% for ALLHAT, Framingham, and reviewers' judgment, respectively. Using these 3 criteria, relative risks (95% CI) for new-onset HF compared with chlorthalidone were, respectively, 1.46 (1.27-1.68), 1.42 (1.25-1.62), and 1.45 (1.28-1.64) for amlodipine; 1.18 (1.02-1.28), 1.13 (0.99-1.30), and 1.15 (1.01-1.32) for lisinopril; and 1.79 (1.51-2.11), 1.71 (1.46-2.00), and 1.80 (1.55-2.10) for doxazosin.


CONCLUSIONS
An independent review of source documentation showed a high degree of agreement with the HF diagnoses assigned by site physicians and confirmed the higher risk of HF associated with first-step therapy using amlodipine, lisinopril, or doxazosin compared with chlorthalidone. Thiazide-type diuretics should be the preferred first-step therapy for prevention of HF in high-risk patients with hypertension.
Einhorn
Paula T
PT
National Heart, Lung, and Blood Institute, Division of Epidemiology and Clinical Applications, Bethesda, MD 20892-7936, USA. einhornp@mail.nih.gov
Davis
Barry R
BR
Massie
Barry M
BM
Cushman
William C
WC
Piller
Linda B
LB
Simpson
Lara M
LM
Levy
Daniel
D
Nwachuku
Chuke E
CE
Black
Henry R
HR
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D017311:Amlodipine / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D015897:Comorbidity; D004311:Double-Blind Method; D017292:Doxazosin / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology; D017706:Lisinopril / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use
D000317:Adrenergic alpha-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D049993:Sodium Chloride Symporter Inhibitors; D017311:Amlodipine; D017706:Lisinopril; D017292:Doxazosin