Treatment of Hypertension with Hydralazine
Primary Recommendation
Hydralazine is not recommended as monotherapy for the treatment of primary hypertension in general adult populations and should be avoided as a first-line agent. 1, 2
Evidence-Based Rationale
Why Hydralazine is Not Appropriate for Primary Hypertension
No randomized controlled trial evidence exists demonstrating that hydralazine prevents cardiovascular events in primary hypertension, according to a Cochrane systematic review that found zero eligible RCTs comparing hydralazine to placebo for mortality or morbidity outcomes 3
Hydralazine monotherapy causes significant adverse effects including reflex tachycardia and sodium/water retention, requiring mandatory concurrent use of a beta-blocker and diuretic to counteract these effects 1, 2, 4
Risk of provoking angina makes hydralazine particularly dangerous in patients with suspected coronary artery disease, as the myocardial stimulation can cause anginal attacks, ECG changes of ischemia, and has been implicated in myocardial infarction 1, 4
Drug-induced lupus syndrome occurs with total daily doses exceeding 150 mg, limiting its long-term use 2
When Hydralazine IS Appropriately Used
Heart Failure with Reduced Ejection Fraction (HFrEF)
The only evidence-based indication for scheduled hydralazine therapy is in combination with isosorbide dinitrate for specific heart failure populations:
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 should receive hydralazine 37.5-75 mg combined with isosorbide dinitrate 20-40 mg three times daily 1, 2
This combination produces a 43% relative risk reduction in mortality and 33% reduction in hospitalizations in this population 2
The benefit requires three-times-daily dosing at target doses—lower doses or less frequent administration have not demonstrated mortality benefit 2
Non-African American patients with HFrEF may receive hydralazine-isosorbide dinitrate as add-on therapy for blood pressure control, though evidence is weaker (Class IIa recommendation) 1
Patients intolerant of ACE inhibitors, ARBs, or ARNIs may receive this combination as an alternative, though evidence in this population is limited 1, 2
Resistant Hypertension (Fifth-Line Agent Only)
Hydralazine may be considered as a fifth-line agent for resistant hypertension, but only when combined with a beta-blocker and diuretic 2
This represents a last-resort option after failure of preferred agents including ACE inhibitors, ARBs, calcium channel blockers, and thiazide diuretics 2
Acute/Emergency Use
Appropriate Emergency Indications
Hypertensive emergencies in eclampsia represent the primary acute indication, with initial dosing of 5-10 mg IV bolus, repeated every 20-30 minutes as needed 5
For obstetrical patients with severe hypertension, the American College of Obstetricians and Gynecologists recommends 5-10 mg IV initially, with subsequent doses every 20-30 minutes 5
Why Hydralazine is NOT First-Line for Most Hypertensive Emergencies
Unpredictable blood pressure response and prolonged duration of action (2-4 hours) make hydralazine undesirable as a first-line agent for most acute hypertensive situations 2, 6, 5
Highly variable effects were demonstrated in a prospective study where 94 hospitalized patients received hydralazine with BP reductions of 24/9 ± 29/15 mmHg—the wide standard deviation indicates unpredictability, and 11 patients developed hypotension 7
Preferred alternatives for non-obstetrical emergencies include nicardipine (5-15 mg/h IV), labetalol (20-80 mg IV bolus every 10 minutes), or clevidipine, which offer more predictable and titratable effects 5, 8
Critical Clinical Pitfalls
Common Misuse in Hospital Settings
A prospective study found that only 2% of patients receiving IV hydralazine had evidence of urgent hypertensive conditions, indicating widespread inappropriate use 7
Avoid administering hydralazine for non-urgent hypertension in hospitalized patients, as it may cause harm through unpredictable hypotension 7
Do not give hydralazine when diastolic BP is already low (<60 mmHg), as this can lead to excessive blood pressure lowering 6
Mandatory Concurrent Therapy
Never use hydralazine alone for chronic hypertension—it must be combined with a beta-blocker (to prevent reflex tachycardia) and a diuretic (to prevent sodium/water retention) 1, 2, 4
When used in heart failure, hydralazine must be combined with isosorbide dinitrate to reduce nitrate tolerance and achieve mortality benefit 1
Monitoring Requirements
Complete blood counts and antinuclear antibody titers should be obtained before and periodically during prolonged therapy, even in asymptomatic patients 4
Monitor for peripheral neuritis (paresthesia, numbness, tingling), which may require pyridoxine supplementation 4
Watch for blood dyscrasias including hemolytic anemia, leukopenia, agranulocytosis, and purpura—discontinue if these develop 4
Specific Contraindications
Avoid in advanced aortic stenosis due to unpredictable blood pressure effects 2
Use with extreme caution in coronary artery disease due to risk of precipitating angina or myocardial infarction 1, 4
Avoid in acute aortic dissection—use esmolol or labetalol instead 5
Practical Algorithm for Hydralazine Use
Step 1: Determine if Hydralazine is Indicated
Is this a self-identified African American patient with NYHA class III-IV HFrEF on optimal therapy? → YES: Use hydralazine-isosorbide dinitrate combination 2
Is this eclampsia/severe hypertension in pregnancy? → YES: Consider hydralazine 5-10 mg IV 5
Is this primary hypertension without heart failure? → NO: Do not use hydralazine as monotherapy 1, 2, 3
Step 2: If Using for HFrEF
Start with hydralazine 37.5 mg + isosorbide dinitrate 20 mg three times daily 2
Titrate to target dose of 75 mg + 40 mg three times daily 2
Ensure concurrent beta-blocker and diuretic therapy 2
Monitor for headache, GI complaints, and adherence issues 1