November
11, 2004
New Orleans, LA - The
African-American Heart Failure Trial (A-HeFT) was terminated
early due to overwhelming evidence that the combination of
isosorbide dinitrate and hydralazine reduces mortality in black
patients with heart failure. The results of the study were
presented at the 2004 American Heart Association Scientific
Session and published in the November 11, 2004 issue of the New
England Journal of Medicine by Anne L. Taylor, et. al., from the
University of Minnesota.
The study sought to demonstrate
that augmentation of nitric oxide bioavailability in black
patients with heart failure was a possible alternative or
supplemental approach to slow or reverse progressive heart
failure. In previous studies, it has been suggested that black
patients may have a less active renin-angiotensin system and a
lower bioavailability of nitric oxide than white patients,
making them an ideal target population for this type of
treatment.
Patients selected for the
randomized, placebo-controlled, double blind trial came from 161
centers in the U.S., were over eighteen years of age, were
self-identified as black, and had NYHA class III or IV heart
failure for at least three months prior to randomization.
These 1050 patients were
randomized into a treatment group of 518 who received 20mg
nitric oxide and 37.5mg hydralazine hydrochloride combination
tablets, and another group of 532 who received placebo. The dose
in the treatment group was increased to two tablets three times
daily once the absence of intolerable side effects was
established. Patients were followed for eighteen months, with
assessment of left ventricle ejection fraction, wall thickness,
diastolic dimension, level of B natriuretic peptide and quality
of life every three months.
The primary end point for the
trial was a composite score of weighted values for death from
any cause, first hospitalization for heart failure, and change
in quality of life according to the Minnesota Living with Heart
Failure questionnaire.
The trial was halted due to a
significantly higher mortality rate in the placebo group than in
the group given isosorbide dinitrate plus hydralazine. There
was a 43 percent reduction in the mortality rate for the
treatment group (P=0.01).
This finding provides strong
evidence that the therapy of isosorbide dinitrate plus
hydralazine in black patients can slow the progression of heart
failure and reduce mortality when added to current standard
neurohormonal treatments.
Co-authors: Susan Ziesche, R.N.,
Clyde Yancy, M.D., Peter Carson, M.D., Ralph D’Agostino, Jr.,
Ph.D., Keith Ferdinand, M.D., Malcolm Taylor, M.D., Kirkwood
Adams, M.D., Michael Sabolinski, M.D., Manuel Worcel, M.D., and
Jay N. Cohn, M.D. for the African-American Heart Failure Trial
Investigators. |