The combination of a direct arterial vasodilator (hydralazine) and a long acting nitrate (isosorbide mononitrate or isosorbide dinitrate) is recommended in patients who are not able to tolerate an ACE inhibitor and angiotensin receptor blocker (class IIa, level of evidence B). The most common reasons that a person would not be able to tolerate these medications would be renal insufficiency, hypotension or angioedema.

The hemodynamic effects of using the combination of hydralazine and nitrates are similar to using an ACE inhibitor or angiotensin receptor blocker (ARB). ACE inhibitors/ARBs reduce afterload by blocking angiotensin II (which is vasoconstrictor) and reduce preload by blocking aldosterone (which normally promotes sodium and water retention). Hydralazine reduces afterload by directly dilating the arteries and long acting nitrates reduce preload by their vasodilator effects. The major difference between using an ACE inhibitor/ARB versus a combination of hydralazine/nitrates is the former blocks the neurohormonal mechanism that is overactive in heart failure patients that leads to negative myocardial remodeling and the latter does not.