Dilemmas With Race and Heart Failure Treatment.

Abstract

The combination of hydralazine and isosorbide dinitrate (H+ISDN) provides balanced vasodilatation, resulting in afterload and preload reductions in heart failure (HF). Both the V-HeFT (Vasodilator Heart Failure Trials) I and II showed improvement in functional capacity and ejection fraction with the use of this combination in HF patients with reduced ejection fraction.1 Subsequent secondary analysis of the V-HeFT data suggested that there might be a race-dependent response to H+ISDN therapy, with blacks deriving more benefit.1 In parallel, there was progress in understanding the role of oxidative stress in HF, varying racial trends in oxidative stress, and the role of H+ISDN in this respect, with ISDN donating nitric oxide and hydralazine being an antioxidant. The hypothesis drawn from these observations was tested in A-HeFT (African-American Heart Failure Trial), which was terminated early because of a 43% relative risk reduction in mortality with H+ISDN observed during data monitoring and led to the approval of BiDil (fixed-dose H+ISDN formulation used in A-HeFT) for the treatment of HF in self-identified blacks.2 This approval was the first where race was used to identify the target population. Although A-HeFT showed the efficacy of H+ISDN in blacks, it did not show H+ISDN to be nonefficacious in non-blacks. Although non-blacks patients did not seem to derive mortality benefit in a retrospective analysis of V-HeFT I, this subgroup finding should be viewed with caution. Rather than reviewing an individual subgroup, the statistical standard is to assess treatment-by-subgroup interaction, which was not …