Is hydralazine (hypertension medication) used to treat hypertension (HTN)?

Hydralazine for Hypertension

Hydralazine is used to treat hypertension, but only as a late-line agent after optimizing first-line therapies, and it must always be combined with a beta-blocker and diuretic to prevent serious adverse effects. 1, 2

Clinical Positioning in Hypertension Management

Not a First-Line Agent

• Hydralazine is recommended as a fifth-line agent for resistant hypertension, only after maximizing ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists, and thiazide diuretics 2
• The European Society of Cardiology recommends hydralazine when hypertension persists despite treatment with combinations of ACE inhibitors (or ARBs), beta-blockers, MRAs, and diuretics (Class I, Level A recommendation) 1

Why Hydralazine Is Not Preferred

• No randomized controlled trial evidence exists comparing hydralazine to placebo for mortality, morbidity, or blood pressure outcomes in primary hypertension 3, 4
• The drug causes reflex tachycardia and sodium/water retention, requiring mandatory concurrent therapy with beta-blockers and diuretics 2, 5
• Hydralazine has been largely replaced by newer antihypertensive drugs with more acceptable tolerability profiles 3

Mandatory Combination Therapy Requirements

Essential Concurrent Medications

• Beta-blockers must be added to control reflex tachycardia when using hydralazine 2, 5
• Thiazide or thiazide-like diuretics must be included to counteract sodium retention and fluid accumulation 2, 5
• The American College of Cardiology explicitly recommends avoiding hydralazine as monotherapy for chronic hypertension 5

Specific Clinical Context Where Hydralazine Has Strong Evidence

Heart Failure with Reduced Ejection Fraction

• Hydralazine combined with isosorbide dinitrate is recommended for self-identified Black patients with NYHA class III-IV heart failure who remain symptomatic despite optimal therapy (Class I, Level A recommendation) 1, 5
• This combination reduced mortality by 43% and hospitalizations by 33% in the A-HeFT trial 5
• For non-Black patients with heart failure and hypertension, hydralazine-isosorbide may be beneficial for blood pressure control (Class IIa, Level C recommendation) 1

Serious Safety Concerns

Drug-Induced Lupus and ANCA Vasculitis

• Total daily doses must be kept below 150 mg to avoid drug-induced systemic lupus erythematosus 2
• Hydralazine can cause severe acute kidney injury resulting in chronic kidney disease or death through ANCA-associated vasculitis 6
• Other serious adverse effects include reflex tachycardia, hemolytic anemia, vasculitis, and glomerulonephritis 3, 4

Acute Hypertensive Management

• Hydralazine is not a first-line agent for most acute hypertensive emergencies due to unpredictable blood pressure responses and prolonged duration of action 5, 7
• The exception is eclampsia and preeclampsia, where hydralazine's safety has been demonstrated 8

Clinical Algorithm for Hydralazine Use

Step 1: Optimize first-line agents (ACE inhibitor/ARB, beta-blocker, MRA, thiazide diuretic) 1, 2

Step 2: If blood pressure remains uncontrolled, add amlodipine or felodipine before considering hydralazine 1, 7

Step 3: Only if blood pressure remains elevated after the above steps, add hydralazine with mandatory beta-blocker and diuretic already in place 1, 2

Step 4: Keep hydralazine dose below 150 mg daily and monitor for lupus-like symptoms 2

Key Pitfall to Avoid

• Never use hydralazine without concurrent beta-blocker and diuretic therapy in chronic hypertension management, as this will cause reflex tachycardia and fluid retention that can worsen outcomes 2, 5