What is the role of hydralazine–isosorbide dinitrate therapy in HF?

• A. Primary therapy for all HF.
• B. Only used in acute decompensation.
• C. Add-on therapy for HFrEF, particularly in African American patients or those intolerant to ACE inhibitors/ARBs, improving survival.
• D. Not recommended due to hypotension.

Answer: (C)

Hydralazine–isosorbide dinitrate is best understood as an add-on therapy for heart failure with reduced ejection fraction (HFrEF) in patients who remain symptomatic despite guideline-directed medical therapy, especially when an ACE inhibitor or ARB cannot be used or in African American patients who show mortality benefit with this combination.

The two drugs work synergistically: hydralazine primarily lowers afterload by dilating arteries, which reduces the heart’s work to eject blood, while isosorbide dinitrate mainly lowers preload by venodilation, decreasing filling pressures and wall stress. Together, they improve cardiac output and relieve symptoms, and they have been shown to reduce mortality and heart-failure–related hospitalizations in the right population.

The strongest evidence comes from trials in African American patients with HFrEF on standard therapy, where adding this combination significantly improved survival. Because of that, guidelines endorse it as add-on therapy for patients who are intolerant to ACE inhibitors or ARBs or who belong to that high-benefit group, rather than as a universal first-line treatment for all HF patients.

This therapy is not a first-line treatment for all heart failure, nor is it reserved only for acute decompensation. It fits into the broader management plan when patients with HFrEF continue to have symptoms despite optimal therapy, with careful attention to blood pressure and tolerability, since hypotension and headaches are potential side effects.