Hydralazine Use in Heart Failure with Reduced Ejection Fraction

Appropriate Scheduled Use

The American College of Cardiology recommends hydralazine combined with isosorbide dinitrate as scheduled therapy three times daily for self-identified African American patients with NYHA class III-IV HFrEF who remain symptomatic despite optimal therapy with ACE inhibitors, beta-blockers, and mineralocorticoid receptor antagonists 1, 2, 3
This combination reduces both mortality (43% relative risk reduction) and hospitalizations (33% relative risk reduction) in patients with HFrEF 4
The initial dose of hydralazine with isosorbide dinitrate is 37.5 mg with 20 mg three times daily, with a target dose of 75 mg with 40 mg three times daily 1
The benefit seen in clinical trials was only achieved at these higher doses with three-times-daily dosing—lower doses or less frequent administration have not demonstrated the same mortality benefit 2
Patients intolerant of ACE inhibitors, ARBs, or ARNIs may receive scheduled hydralazine-isosorbide dinitrate as an alternative, though evidence is weaker in this population 2, 4

For hypertensive emergencies, hydralazine is given as intermittent IV boluses, with an initial dose of 10 mg slow IV infusion, repeated every 4-6 hours as needed 5
Blood pressure begins to decrease within 10-30 minutes with effects lasting 2-4 hours, but the unpredictability and prolonged duration make it undesirable as a first-line agent for most acute situations 5

Common adverse effects of hydralazine include headache, dizziness, and gastrointestinal complaints, which may limit adherence to scheduled regimens 4

The American Heart Association recommends hydralazine combined with isosorbide dinitrate for African American patients with heart failure with reduced ejection fraction (HFrEF) to reduce morbidity and mortality, effectively lowering blood pressure 6, 7
The American Heart Association advises against using hydralazine without a nitrate in heart failure with reduced ejection fraction, as it is associated with harm (Class III) 6, 8

The American Society of Hypertension suggests considering hydralazine as a fifth-line agent for resistant hypertension, but it must be combined with a beta-blocker and diuretic to counteract reflex tachycardia and sodium retention 9
Total daily doses of hydralazine should be less than 150 mg to avoid drug-induced systemic lupus erythematosus 9

Hydralazine causes reflex tachycardia and sodium/water retention, requiring concurrent beta-blocker and diuretic therapy 9
The American College of Cardiology recommends avoiding hydralazine as monotherapy for chronic hypertension, as it must be combined with a beta-blocker and diuretic 9, 10

The American Heart Association recommends that hydralazine should be avoided in patients with advanced aortic stenosis due to its potential to cause unpredictable blood pressure effects 11, 12

The American College of Cardiology recommends that hydralazine is not a first-line agent for most acute hypertensive emergencies due to its unpredictable blood pressure response and prolonged duration of action 11, 12

The American College of Cardiology recommends the combination of hydralazine and isosorbide dinitrate for self-identified African American patients with NYHA class III-IV heart failure who remain symptomatic despite optimal therapy, with a strength of evidence classified as a Class I recommendation 13, 14

The American Heart Association recommends hydralazine in combination with isosorbide dinitrate as scheduled therapy for specific heart failure populations, or as a last-resort agent in resistant hypertension when combined with beta-blockers and diuretics 15, 16, 17
The American College of Cardiology suggests that self-identified African American patients with NYHA class III-IV heart failure with reduced ejection fraction who remain symptomatic despite optimal therapy should receive hydralazine 37.5-75 mg combined with isosorbide dinitrate 20-40 mg three times daily (Class I, Level A evidence) 16, 17, 18
Non-black patients with heart failure with reduced ejection fraction may receive hydralazine-isosorbide dinitrate for blood pressure control as add-on therapy (Class IIa, Level C evidence) 18
Patients intolerant of ACE inhibitors, ARBs, or ARNIs may receive this combination as an alternative, though supporting evidence is limited 19, 18

The American Heart Association recommends monitoring serum potassium and renal function when hydralazine is used with ACE inhibitors/ARBs and aldosterone antagonists 17, 18

The American College of Cardiology advises against using hydralazine monotherapy in heart failure with reduced ejection fraction (Class III Harm) 15, 17
The American Heart Association suggests that hydralazine may increase the risk of adverse effects when used with MAO inhibitors, diazoxide, and other agents 19

The American College of Cardiology recommends prioritizing guideline-directed medical therapy before considering hydralazine, including ACE inhibitors or ARBs, beta-blockers, aldosterone antagonists, and diuretics 15, 17, 18
The American Heart Association suggests avoiding non-dihydropyridine calcium channel blockers, moxonidine, and alpha-blockers in heart failure with reduced ejection fraction unless all other options are exhausted 15, 17, 18