title: Exploring the potential synergistic action of spironolactone on nitric oxide-enhancing therapy: insights from the African-American Heart Failure Trial.
abstract: BACKGROUND
  To investigate if treatment with an aldosterone antagonist affects the outcomes of treatment by fixed dose combination of isosorbide dinitrate/hydralazine (FDC I/H) or placebo in black heart failure (HF) patients treated with contemporary HF medications. In the African-American Heart Failure Trial (A-HeFT), FDC I/H was effective in reducing mortality and improving event-free survival. The beneficial effects of aldosterone antagonist (spironolactone [SP]), however have not been adequately assessed in black patients with or without the use of FDC I/H.
  
  
  RESULTS
  A retrospective analysis was performed in A-HeFT data base (n = 1050) to determine the effect of using SP (39% of patients) on outcomes. Baseline comparisons were done by 2-sample t-test or Fisher's exact test. Kaplan-Meier survival analyses were used for comparing between and within groups for outcomes. SP had no effect on mortality, event-free survival, or first HF hospitalization in the overall A-HeFT population. However, SP decreased mortality risk in the FDC I/H group by 59% (P = .03), and a favorable trend was noted on event-free survival and first HF hospitalization. In contrast, the use of SP was not associated with a decrease in mortality or HF hospitalizations in the placebo group.
  
  
  CONCLUSIONS
  This study suggests that in black patients with systolic heart failure on standard therapy of beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists, the beneficial effects of aldosterone antagonists require a background therapy of FDC I/H.
authors.affiliation: Wayne State University, Detroit, MI 48201, USA. jghali@med.wayne.edu
authors.forename: Jalal K
authors.initials: JK
authors.lastname: Ghali
authors.forename: S William
authors.initials: SW
authors.lastname: Tam
authors.forename: Michael L
authors.initials: ML
authors.lastname: Sabolinski
authors.forename: Anne L
authors.initials: AL
authors.lastname: Taylor
authors.forename: Joann
authors.initials: J
authors.lastname: Lindenfeld
authors.forename: Jay N
authors.initials: JN
authors.lastname: Cohn
authors.forename: Manuel
authors.initials: M
authors.lastname: Worcel
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D017326:Clinical Trials, Phase III as Topic / Q000379:methods; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D006830:Hydralazine / Q000008:administration & dosage*; D007548:Isosorbide Dinitrate / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic / Q000379:methods; D020030:Nitric Oxide Donors / Q000008:administration & dosage*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012189:Retrospective Studies; D013148:Spironolactone / Q000008:administration & dosage*
chemical_list: D004338:Drug Combinations; D020030:Nitric Oxide Donors; C431665:isosorbide-hydralazine combination; D006830:Hydralazine; D013148:Spironolactone; D007548:Isosorbide Dinitrate