Isosorbide Dinitrate and Hydralazine in a Fixed-Dose Combination Produces Further Regression of Left Ventricular Remodeling in a Well-Treated Black Population With Heart Failure: Results From A-HeFT

Jay N. Cohn, S. William Tam, Inder S. Anand, Anne L. Taylor, Michael L. Sabolinski, Manuel Worcel

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60 Scopus citations

Abstract

Background: Isosorbide dinitrate combined with hydralazine therapy compared with placebo in patients with heart failure resulted in a sustained increase in left ventricular (LV) ejection fraction (EF) indicative of regression of LV remodeling in the first Vasodilator-Heart Failure Trial (V-HeFT-I) in patients receiving only digoxin and diuretic. In the African-American Heart Failure Trial (A-HeFT) a fixed-dose combination resulted in a 43% reduction in mortality in 1050 black patients with heart failure already treated with recommended neurohormonal inhibiting drugs. Whether the fixed-dose combination produces a further regression of LV remodeling when added to renin-angiotensin and sympathetic inhibitors has not been documented. Methods and Results: Echocardiograms at baseline and 6 months after randomization to placebo or a fixed-dose combination of isosorbide dinitrate/hydralazine (FDC I/H) were analyzed in 678 A-HeFT participants in a core laboratory. LVEF rose by 2.8 EF units in the FDC I/H group versus 0.8% in the control group (P < .01), LV mass index fell by 7.4 g/m2 in the FDC I/H group versus an increase of 1.4 g/m2 in the placebo group (P < .05), LV diastolic transverse diameter fell by 2.2 mm in FDC I/H and was unchanged in placebo (P < .01), and the LV systolic and diastolic sphericity indices improved in the FDC I/H group but remained unchanged in the placebo group. The mean plasma B-type natriuretic peptide (BNP) also measured in a core laboratory fell in the FDC I/H group by 39 pg/mL compared with 8 pg/mL in the placebo group (P = .05). Conclusions: A fixed-dose combination of I/H produces regression of LV remodeling when added to background therapy with renin-angiotensin and sympathetic inhibitors in black patients with heart failure. This remodeling benefit may explain at least in part the mortality reduction in A-HeFT.

Original languageEnglish (US)
Pages (from-to)331-339
Number of pages9
JournalJournal of cardiac failure
Volume13
Issue number5
DOIs
StatePublished - Jun 2007

Bibliographical note

Funding Information:
A-HeFT was supported by NitroMed. The fixed-dose combination of isosorbide dinitrate and hydralazine was provided as BiDil.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

  • Echocardiography
  • heart failure
  • mortality
  • nitric oxide
  • remodeling

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