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

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;314:1547-52 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

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

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

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

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

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;1747-1753

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

Results

50days

Event-free survival

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

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

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