Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine

Consistency across subgroups in the African-American Heart Failure Trial

Anne L. Taylor, Susan Ziesche, Clyde W. Yancy, Peter Carson, Keith Ferdinand, Malcolm Taylor, Kirkwood Adams, Adeoye Y. Olukotun, Elizabeth Ofili, S. William Tam, Michael L. Sabolinski, Manuel Worcel, Jay N. Cohn

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

BACKGROUND - We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality. METHODS AND RESULTS - Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P<0.001) and a 39% reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at ≈50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012). CONCLUSIONS - FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.

Original languageEnglish (US)
Pages (from-to)1747-1753
Number of pages7
JournalCirculation
Volume115
Issue number13
DOIs
StatePublished - Apr 1 2007

Fingerprint

African Americans
Disease-Free Survival
Hospitalization
Heart Failure
Mortality
isosorbide-hydralazine combination
Isosorbide Dinitrate
Hydralazine
Kaplan-Meier Estimate
Risk Reduction Behavior
Therapeutics
Chronic Renal Insufficiency
Cause of Death
Diabetes Mellitus
Quality of Life
Blood Pressure

Keywords

  • African Americans
  • Cardiovascular diseases
  • Heart failure
  • Nitric oxide
  • Trials

Cite this

Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine : Consistency across subgroups in the African-American Heart Failure Trial. / Taylor, Anne L.; Ziesche, Susan; Yancy, Clyde W.; Carson, Peter; Ferdinand, Keith; Taylor, Malcolm; Adams, Kirkwood; Olukotun, Adeoye Y.; Ofili, Elizabeth; Tam, S. William; Sabolinski, Michael L.; Worcel, Manuel; Cohn, Jay N.

In: Circulation, Vol. 115, No. 13, 01.04.2007, p. 1747-1753.

Research output: Contribution to journalArticle

Taylor, Anne L. ; Ziesche, Susan ; Yancy, Clyde W. ; Carson, Peter ; Ferdinand, Keith ; Taylor, Malcolm ; Adams, Kirkwood ; Olukotun, Adeoye Y. ; Ofili, Elizabeth ; Tam, S. William ; Sabolinski, Michael L. ; Worcel, Manuel ; Cohn, Jay N. / Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine : Consistency across subgroups in the African-American Heart Failure Trial. In: Circulation. 2007 ; Vol. 115, No. 13. pp. 1747-1753.
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abstract = "BACKGROUND - We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality. METHODS AND RESULTS - Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37{\%} improvement in event-free survival (P<0.001) and a 39{\%} reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at ≈50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75{\%} (P=0.012). CONCLUSIONS - FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.",
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T1 - Early and sustained benefit on event-free survival and heart failure hospitalization from fixed-dose combination of isosorbide dinitrate/hydralazine

T2 - Consistency across subgroups in the African-American Heart Failure Trial

AU - Taylor, Anne L.

AU - Ziesche, Susan

AU - Yancy, Clyde W.

AU - Carson, Peter

AU - Ferdinand, Keith

AU - Taylor, Malcolm

AU - Adams, Kirkwood

AU - Olukotun, Adeoye Y.

AU - Ofili, Elizabeth

AU - Tam, S. William

AU - Sabolinski, Michael L.

AU - Worcel, Manuel

AU - Cohn, Jay N.

PY - 2007/4/1

Y1 - 2007/4/1

N2 - BACKGROUND - We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality. METHODS AND RESULTS - Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P<0.001) and a 39% reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at ≈50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012). CONCLUSIONS - FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.

AB - BACKGROUND - We previously reported that the fixed-dose combination of isosorbide dinitrate and hydralazine hydrochloride (FDC I/H) significantly decreased the risk of all-cause death and first hospitalization for heart failure (HF) and improved quality of life in patients with New York Heart Association class III or IV heart failure in the African-American Heart Failure Trial (A-HeFT). The current analyses further define the effect of FDC I/H on the timing of event-free survival (mortality or first hospitalization for HF) and time to first hospitalization for HF, as well as effects by subgroups and effects on cause-specific mortality. METHODS AND RESULTS - Kaplan-Meier analyses of the 1050 A-HeFT patients on standard neurohormonal blockade demonstrated that FDC I/H produced a 37% improvement in event-free survival (P<0.001) and a 39% reduction in the risk for first hospitalization for HF (P<0.001). These benefits appeared to emerge early (at ≈50 days of treatment) and were sustained through the duration of the trial. Subgroup analyses of treatment effect by age, sex, baseline blood pressure, history of chronic renal insufficiency, presence of diabetes mellitus, cause of HF, and baseline medication usage demonstrated consistent beneficial effect of FDC I/H on the primary composite score and event-free survival across all subgroups. Mortality from pump failure was reduced by 75% (P=0.012). CONCLUSIONS - FDC I/H treatment of black patients with moderate to severe HF who were taking neurohormonal blockers produced early and sustained significant improvement in event-free survival and hospitalization for HF in the A-HeFT cohort, with significant reduction in mortality from cardiovascular and pump failure deaths. The treatment effects on the primary composite end point and event-free survival were consistent across subgroups.

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