2. The African-American Heart Failure Trial (A-HeFT)

3. Background The first Vasodilator Heart Failure Trial (V-HeFT I)
benefit of combining the nitric oxide donor isosorbide
dinitrate with the antioxidant hydralazine in patients with
mild-to-severe heart failure. but long-term benefit not evaluated
N Engl J Med 1986;314:
Black ,less active renin-angiotensin system and lower bioavailability of NO
Clin Pharmacol Ther 1997;62:436-43
Retrospective analysis strongly suggestive : Black pat. Significant response to isosorbide dinitrate and hydralazine
J Card Fail 1999;5:178-87

4. Methods Total 1050 black patients, >18 yrs, 169 centers in USA
placebo-controlled double blind
NYHA III or IV with dilated ventricle
isosorbide dinitrate and hydralazine ,stendard Tx.
Vs Placebo, stendard Tx.
The primary end point (composite score)
(1) any cause of death
(2) a first hospitalization for heart failure
(3) change in the quality of life (QoL)
ACEi, ARB, B-blocker, diuretics,
digoxin, spironolactone

5. Isosorbide dinitrate 1 tablet (37.5mg) tid -> total 225mg/day
Hydralazine 1 tablet (20mg) tid -> total 120mg/day
(For 18 months)
2D echo for LV function & BNP : at 6 months
QoL : Minnesota Living with Heart Failure Questionnaire
- every 3 months

6. Exclusion criteria - pregnant
- acute coronary syndrome, or stroke within the previous 3months
- cardiac surgery or PCI within 3 months
- significant valvular heart disease
- cardiac arrest or life-threatening within 3 months
- cardiac transplantation
- symptomatic hypotension;
- inability to comprehend or complete the quality-of-life (QoL)
- contraindications to nitrate or hydralazine therapy

12. Conclusions
The addition of a fixed dose of isosorbide dinitrate plus hydralazine to standard therapy
for heart failure including neurohormonal blockers is efficacious and increases survival
among black patients with advanced heart failure

13. 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 (A-HeFT)
Circulation 2007;115;

14. Background
The fixed dose combination of isosorbide dinitrate and hydalazine hydrochloride (FDC I/H)
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

15. Results

17. 50days

20. Event-free survival

21. Lupus - like syndrome d/t hydralazine
Lancet. 1980;1:1107–1109

22. Discussion Motality from pump failure was significant reduced
- hemodynamic improvement LV function
- inhibiton of LV remodeling
FDC I/H : enhanced NO bioavailability ??
Limitation
- inadequate sample size
- calssification of patients into incorrect subgroups
- low power to test for potential interaction

23. Conclusions
(1) FDC I/H treatment of black patients with moderate to severe HF produced early and sustained significant improvement in event-free survival and hospitalization with significant reduction in mortality from cardiovascular and pump failure deaths
(2) the primary composite end point and event-free
survival were consistent across subgroups