A-HeFT, V-HeFT, V-HeFT - Hydralazine+nitrate in HFrEF


Results in context

  • V-HeFT was the first trial demonstrating a mortality benefit with any drug for heart failure. It was published prior to studies showing benefits of ACEI/ARB, beta-blocker, and mineralocorticoid receptor antagonists
    • V-HeFT demonstrated that hydralazine/ISDN improved outcomes in HF, & that this was not due to a generic "vasodilator" effect, as demonstrated by an INCREASE in mortality with prazosin
  • V-HeFT II came hot off the heels of CONSENSUS (published in 1987), which demonstrated a great benefit to ACEI in NYHA class IV HF
    • Although the results of the comparison of enalapril to hydralazine/ISDN in V-HeFT II were not "statistically" significant, with a p=0.08 for mortality, it provided convincing evidence of the superiority of RAAS inhibition with an ACEI over hydralazine/ISDN
    • After V-HeFT II, hydralazine/ISDN was put on the sideline & no further outcome RCTs were conducted until A-HeFT
  • In 1999, subgroup analyses of the two V-HeFT trials demonstrated borderline race-based differences in response to hydralazine/ISDN (p=0.09-0.11 for interaction by race) & formed the basis to conduct A-HeFT
    • Mortality in V-HeFT according to race
      • Black: Hydralazine/ISDN 9.7%, placebo 17.3% (NNT 14)
      • White: Hydralazine/ISDN 16.9%, placebo 18.8%
    • Mortality in V-HeFT II according to race
      • Black: Enalapril 12.8%, hydralazine/ISDN 12.9%
      • White: Enalapril 11.0%, hydralazine/ISDN 14.9% (NNT 26)
    • Of note, these analyses were underpowered to rule out a benefit of hydralazine/ISDN in whites
  • A-HeFT demonstrated a large reduction in mortality with hydralazine/ISDN in black HFrEF patients with mostly NYHA functional class III
    • Hydralazine/ISDN therefore has a role as add-on therapy to ACEI/ARB in symptomatic black HFrEF patients who can tolerate additional vasodilator therapy
    •  It's unclear based on the available evidence if the results of A-HeFT can translate to non-black HFrEF patients. Given the borderline subgroup analyses noted above, hydralazine/ISDN likely still has a role for non-black patients as a 3rd line agent in those who cannot tolerated an ACEI or ARB due to hyperkalemia or renal dysfunction.