Is Hydralazine Effective for Blood Pressure Management?
Hydralazine is effective at lowering blood pressure through direct arterial vasodilation, but it should NOT be used as monotherapy for chronic hypertension and is reserved for specific clinical contexts: combined with isosorbide dinitrate in Black patients with advanced heart failure, or as a fifth-line agent in resistant hypertension when combined with beta-blockers and diuretics. 1, 2
Mechanism and Pharmacologic Effectiveness
Hydralazine lowers blood pressure by directly relaxing vascular smooth muscle, preferentially dilating arterioles over veins, which decreases peripheral vascular resistance and reduces diastolic blood pressure more than systolic 3. Peak plasma levels occur 1-2 hours after oral administration, with effects lasting 3-7 hours, though the drug undergoes polymorphic acetylation—slow acetylators achieve higher plasma levels and require lower doses 3.
However, the absence of randomized controlled trials comparing hydralazine to placebo for primary hypertension means its effect on clinical outcomes (mortality, stroke, myocardial infarction) remains uncertain. 4, 5
Appropriate Clinical Contexts for Use
Heart Failure with Reduced Ejection Fraction (Primary Indication)
The American Heart Association gives a Class I, Level A recommendation for hydralazine combined with isosorbide dinitrate (37.5-75 mg/20-40 mg three times daily) in self-identified Black patients with NYHA class III-IV heart failure who remain symptomatic despite optimal therapy with ACE inhibitors/ARBs, beta-blockers, and aldosterone antagonists. 6, 1 This combination reduced mortality by 43% and hospitalizations by 33% in the A-HeFT trial 1, 2.
For non-Black patients with heart failure and reduced ejection fraction, hydralazine-isosorbide dinitrate may be beneficial for blood pressure control as add-on therapy (Class IIa, Level C evidence) 6, 1.
Critical caveat: The American Heart Association explicitly recommends AGAINST using hydralazine without a nitrate in heart failure with reduced ejection fraction (Class III Harm). 1
Resistant Hypertension (Fifth-Line Agent Only)
The American College of Cardiology recommends hydralazine only as a fifth-line agent for resistant hypertension, after maximizing a three-drug regimen and adding a mineralocorticoid receptor antagonist. 2 When used in this context, hydralazine MUST be combined with:
- Beta-blockers to control reflex tachycardia 1, 2
- Thiazide or thiazide-like diuretics to counteract sodium retention and fluid accumulation 1, 2
Acute Hypertensive Situations (Not First-Line)
For hypertensive emergencies, IV hydralazine can be given as 10 mg slow infusion repeated every 4-6 hours, with blood pressure decreasing within 10-30 minutes 1. However, the American Heart Association notes that hydralazine has an unpredictable blood pressure response and prolonged duration of action, making it less desirable as a first-line agent for acute treatment in most patients. 1, 7
Critical Safety Considerations and Pitfalls
Mandatory Concurrent Therapy
Never use hydralazine as monotherapy for chronic hypertension—it causes reflex tachycardia and sodium/water retention that require concurrent beta-blocker and diuretic therapy 1, 2.
Dose Limitations
Keep total daily doses below 150 mg to avoid drug-induced systemic lupus erythematosus. 1, 2 Other reported adverse effects include hemolytic anemia, vasculitis, and glomerulonephritis 4, 5.
Contraindications
Avoid hydralazine in patients with advanced aortic stenosis due to unpredictable blood pressure effects. 1
Dosing Frequency
Hydralazine can be administered twice daily for chronic hypertension when combined with appropriate adjunctive therapy 8. Studies show that 300 mg daily divided into two doses is as effective as four divided doses, with no significant difference in blood pressure control or coefficient of variation (4.1%-4.8% vs 4.0% at baseline) 9. After discontinuation, blood pressure returns halfway to baseline values over 30-140 hours 9.
Bottom Line Algorithm
- For chronic hypertension alone: Do NOT use hydralazine as first-, second-, third-, or fourth-line therapy 2
- For Black patients with NYHA class III-IV HFrEF on optimal therapy: Add hydralazine 37.5-75 mg + isosorbide dinitrate 20-40 mg three times daily 6, 1
- For resistant hypertension after four-drug optimization: Consider hydralazine ONLY if combined with beta-blocker + diuretic, keeping dose <150 mg/day 1, 2
- For acute hypertensive emergencies: Use nicardipine or labetalol first; reserve hydralazine for second-line situations 7