From the Guidelines
Hydralazine should be combined with isosorbide dinitrate for the treatment of heart failure, particularly in patients who cannot tolerate ACE inhibitors or ARBs due to drug intolerance, hypotension, or renal insufficiency. This recommendation is based on the 2013 ACCF/AHA guideline for the management of heart failure, which suggests that a combination of hydralazine and isosorbide dinitrate can be useful to reduce morbidity or mortality in patients with current or prior symptomatic HFrEF 1. The combination therapy, often marketed as BiDil, is recommended at doses of hydralazine 37.5 mg and isosorbide dinitrate 20 mg taken three times daily, titrated to a target dose of hydralazine 75 mg and isosorbide dinitrate 40 mg three times daily as tolerated.
Key Points
- The combination of hydralazine and isosorbide dinitrate has been shown to reduce mortality, but not hospitalizations, in patients with HF treated with digoxin and diuretics but not an ACE inhibitor or beta blocker 1.
- In African American patients, the addition of a fixed-dose combination of hydralazine and isosorbide dinitrate to standard therapy with an ACE inhibitor or ARB, a beta blocker, and an aldosterone antagonist has been shown to offer significant benefit 1.
- The mechanism behind this combination's effectiveness involves complementary actions: hydralazine acts as a direct vasodilator that reduces afterload, while isosorbide dinitrate is a nitrate that increases nitric oxide availability, promoting vasodilation and reducing preload.
Clinical Considerations
- This combination therapy is especially beneficial for patients who cannot tolerate ACE inhibitors or ARBs due to renal dysfunction or angioedema, or as add-on therapy for patients who remain symptomatic despite standard heart failure treatments.
- The particular efficacy of isosorbide dinitrate and hydralazine in African American patients may be due to differences in nitric oxide bioavailability 1.
From the Research
Hydralazine and Isosorbide Dinitrate for Heart Failure
- The combination of hydralazine and isosorbide dinitrate (Hy+ISDN) is used in the treatment of patients with heart failure with reduced ejection fraction (HFrEF) 2.
- This combination has arterial and venous vasodilating properties, which can decrease preload and afterload, and improve left ventricular ejection fraction 2.
- The Hy+ISDN combination is guideline-recommended for HFrEF patients who cannot receive either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers due to intolerance or contraindication, and in self-identified African-American HFrEF patients who are symptomatic despite optimal neurohumoral therapy 2.
- Studies have shown that the combination of isosorbide dinitrate and hydralazine can produce further regression of left ventricular remodeling in well-treated black patients with heart failure 3.
- The fixed-dose combination of isosorbide dinitrate and hydralazine has been shown to reduce morbidity and mortality in African American patients with heart failure 4, 5, 6.
- The mechanism of action of this combination involves the increase of nitric oxide bioavailability and the reduction of oxidative stress, which can improve vascular homeostasis and reduce left ventricular dysfunction 6.