title: 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.
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.
  
  
  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.
authors.affiliation: Cardiovascular Division, Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Jay N
authors.initials: JN
authors.lastname: Cohn
authors.forename: S William
authors.initials: SW
authors.lastname: Tam
authors.forename: Inder S
authors.initials: IS
authors.lastname: Anand
authors.forename: Anne L
authors.initials: AL
authors.lastname: Taylor
authors.forename: Michael L
authors.initials: ML
authors.lastname: Sabolinski
authors.forename: Manuel
authors.initials: M
authors.lastname: Worcel
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000208:ethnology / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology* / Q000627:therapeutic use; D007548:Isosorbide Dinitrate / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D013318:Stroke Volume; D016896:Treatment Outcome; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D020097:Natriuretic Peptide, Brain; D006830:Hydralazine; D007548:Isosorbide Dinitrate