Exploring the Potential Synergistic Action of Spironolactone on Nitric Oxide-Enhancing Therapy

Insights From the African-American Heart Failure Trial

Jalal K. Ghali, S. William Tam, Michael L. Sabolinski, Anne L. Taylor, Joann Lindenfeld, Jay N. Cohn, Manuel Worcel

Research output: Contribution to journalArticle

11 Citations (Scopus)

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. Methods and 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 β-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists, the beneficial effects of aldosterone antagonists require a background therapy of FDC I/H.

Original languageEnglish (US)
Pages (from-to)718-723
Number of pages6
JournalJournal of Cardiac Failure
Volume14
Issue number9
DOIs
StatePublished - Nov 1 2008

Fingerprint

Spironolactone
African Americans
Action Potentials
Nitric Oxide
Heart Failure
Mineralocorticoid Receptor Antagonists
Disease-Free Survival
Hospitalization
Mortality
Therapeutics
Placebos
Systolic Heart Failure
Angiotensin Receptor Antagonists
Kaplan-Meier Estimate
Survival Analysis
Angiotensin-Converting Enzyme Inhibitors
Databases

Keywords

  • Heart failure
  • race

Cite this

Exploring the Potential Synergistic Action of Spironolactone on Nitric Oxide-Enhancing Therapy : Insights From the African-American Heart Failure Trial. / Ghali, Jalal K.; Tam, S. William; Sabolinski, Michael L.; Taylor, Anne L.; Lindenfeld, Joann; Cohn, Jay N.; Worcel, Manuel.

In: Journal of Cardiac Failure, Vol. 14, No. 9, 01.11.2008, p. 718-723.

Research output: Contribution to journalArticle

Ghali, Jalal K. ; Tam, S. William ; Sabolinski, Michael L. ; Taylor, Anne L. ; Lindenfeld, Joann ; Cohn, Jay N. ; Worcel, Manuel. / Exploring the Potential Synergistic Action of Spironolactone on Nitric Oxide-Enhancing Therapy : Insights From the African-American Heart Failure Trial. In: Journal of Cardiac Failure. 2008 ; Vol. 14, No. 9. pp. 718-723.
@article{5762ffad01d048be9cbecfcf12a2f58b,
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. Methods and 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 β-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists, the beneficial effects of aldosterone antagonists require a background therapy of FDC I/H.",
keywords = "Heart failure, race",
author = "Ghali, {Jalal K.} and Tam, {S. William} and Sabolinski, {Michael L.} and Taylor, {Anne L.} and Joann Lindenfeld and Cohn, {Jay N.} and Manuel Worcel",
year = "2008",
month = "11",
day = "1",
doi = "10.1016/j.cardfail.2008.07.189",
language = "English (US)",
volume = "14",
pages = "718--723",
journal = "Journal of Cardiac Failure",
issn = "1071-9164",
publisher = "Churchill Livingstone",
number = "9",

}

TY - JOUR

T1 - Exploring the Potential Synergistic Action of Spironolactone on Nitric Oxide-Enhancing Therapy

T2 - Insights From the African-American Heart Failure Trial

AU - Ghali, Jalal K.

AU - Tam, S. William

AU - Sabolinski, Michael L.

AU - Taylor, Anne L.

AU - Lindenfeld, Joann

AU - Cohn, Jay N.

AU - Worcel, Manuel

PY - 2008/11/1

Y1 - 2008/11/1

N2 - 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. Methods and 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 β-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists, the beneficial effects of aldosterone antagonists require a background therapy of FDC I/H.

AB - 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. Methods and 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 β-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists, the beneficial effects of aldosterone antagonists require a background therapy of FDC I/H.

KW - Heart failure

KW - race

UR - http://www.scopus.com/inward/record.url?scp=55149111172&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=55149111172&partnerID=8YFLogxK

U2 - 10.1016/j.cardfail.2008.07.189

DO - 10.1016/j.cardfail.2008.07.189

M3 - Article

VL - 14

SP - 718

EP - 723

JO - Journal of Cardiac Failure

JF - Journal of Cardiac Failure

SN - 1071-9164

IS - 9

ER -