Journal of Cardiac Failure
Volume 13, Issue 5 , Pages 331-339, June 2007

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, MD

      Affiliations

    • From the Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota
    • Corresponding Author InformationReprint requests: Jay N. Cohn, MD, Professor of Medicine, Cardiovascular Division, MC 508, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455.
    • ,
  • S. William Tam, PhD

      Affiliations

    • NitroMed, Inc., Lexington, Massachusetts
    • ,
  • Inder S. Anand, MD

      Affiliations

    • From the Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota
    • ,
  • Anne L. Taylor, MD

      Affiliations

    • From the Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota
    • ,
  • Michael L. Sabolinski, MD

      Affiliations

    • NitroMed, Inc., Lexington, Massachusetts
    • ,
  • Manuel Worcel, MD

      Affiliations

    • NitroMed, Inc., Lexington, Massachusetts
    • ,
  • for the A-HeFT Investigators

Received 6 November 2006; received in revised form 1 March 2007; accepted 5 March 2007.

Minnesota, Minneapolis; Lexington, Massachusetts

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.

Key Words: Echocardiography, mortality, nitric oxide, heart failure, remodeling

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 All decisions regarding this manuscript were made by a guest editor.A-HeFT was supported by NitroMed. The fixed-dose combination of isosorbide dinitrate and hydralazine was provided as BiDil.All authors have received grant support from NitroMed, Inc (JNC, ISA, ALT), or are employees of NitroMed (MW, MLS, SWT). Dr. Cohn has a royalty relationship with NitroMed based on his patents of the drug combination.

PII: S1071-9164(07)00070-X

doi:10.1016/j.cardfail.2007.03.001

Journal of Cardiac Failure
Volume 13, Issue 5 , Pages 331-339, June 2007

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