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 […]