Miguel Morita Fernandes-Silva et al. Ana Carolina Krachinski de Andrade Gama Gabriela Yumi Konno Saito Bruna Czelusniak Goulart … Even Edilce Mol Marco Stephan Lofrano-Alves
Abstract
The treatment of heart failure (HF) with reduced ejection fraction (HFrEF) has evolved significantly over time, with the emergence of various pharmacotherapies targeting different pathophysiological pathways. While neurohumoral antagonists like angiotensin converting enzyme (ACE) inhibitors and beta-blockers have become first-line therapies, the main paradigm shift occurred with medications with vasodilatory effects, including the combination of hydralazine and isosorbide dinitrate (H-ISDN). Although the role of H-ISDN has been overshadowed over time, it remains significant, particularly in certain populations.
With proven hemodynamic benefits in HF by reducing both preload and afterload, H-ISDN was initially tested in the 1980s in the Vasodilator Heart Failure Trial I (V-HeFT I), with promising results. Nevertheless, subsequent trials like V-HeFT II indicated that ACE inhibitors were superior to H-ISDN in reducing mortality.
Later, post-hoc analyses of V-HeFT trials suggested a potential benefit of H-ISDN among black patients. This prompted the African-American Heart Failure trial (A-HeFT), which demonstrated a significant reduction in mortality with H-ISDN in black patients with HFrEF, who were under standard HF treatment including ACE inhibitors.
Current guidelines recommend H-ISDN in black patients with HFrEF who remain symptomatic despite optimized therapy or in those who cannot tolerate ACE inhibitors or angiotensin receptor blockers. However, the use of H-ISDN in other racial groups and in certain clinical scenarios like decompensated HF or renal failure remains less clear due to limited evidence. In this article, we review the history, pharmacological mechanisms, and clinical evidence for the H-ISDN in the treatment of HFrEF.