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Isosorbide Dinitrate and Hydralazine Combination Therapy Proves Beneficial in Blacks with Heart Failure

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.

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