Isosorbide Dinitrate plus Hydralazine Dosing for Heart Failure
Initial Dosing
- The American Heart Association recommends starting with isosorbide dinitrate 20 mg plus hydralazine 37.5 mg three times daily, then titrating to the target dose of isosorbide dinitrate 40 mg plus hydralazine 75 mg three times daily, for patients with heart failure 1, 2
- When using the medications separately, the initial dose is isosorbide dinitrate 20-30 mg and hydralazine 25-50 mg, both given 3-4 times daily, for patients with heart failure 1, 3
Target Dosing
- The target dose is 40 mg isosorbide dinitrate and 75 mg hydralazine three times daily, achieving a total daily dose of 120 mg isosorbide dinitrate and 225 mg hydralazine, for patients with heart failure 1, 2
- The maximum target dose when using separate formulations is 120 mg isosorbide dinitrate total daily in divided doses and 300 mg hydralazine total daily in divided doses, for patients with heart failure 1, 3
Titration Strategy
- The dose should be increased gradually over several weeks to enhance tolerance and minimize adverse effects, for patients with heart failure 2
- The mean doses achieved in clinical trials were approximately 90 mg isosorbide dinitrate and 175 mg hydralazine total daily, indicating that many patients may not tolerate the full target dose, for patients with heart failure 1, 3
Clinical Context for Use
- The American College of Cardiology recommends this combination for self-identified Black patients with HFrEF (NYHA class III-IV) who remain symptomatic despite optimal therapy with ACE inhibitors/ARBs, beta-blockers, and aldosterone antagonists 4, 2
- The combination can also be used in patients who cannot tolerate ACE inhibitors or ARBs due to drug intolerance, hypotension, or renal insufficiency, for patients with heart failure 3, 2
Mortality Benefit
- This combination provides a 43% relative risk reduction in mortality with a number needed to treat of 7 (standardized to 36 months) and a 33% reduction in heart failure hospitalizations, for patients with heart failure 1, 4, 2
Important Caveats
- Adherence is typically poor due to the three-times-daily dosing schedule, large pill burden, and frequent adverse effects, for patients with heart failure 2