Is hydralazine (Hydralazine) okay to use in reduced heart failure (Heart Failure with Reduced Ejection Fraction)?

Hydralazine in Heart Failure with Reduced Ejection Fraction

Hydralazine alone is not recommended as first-line therapy for heart failure with reduced ejection fraction (HFrEF), but the combination of hydralazine and isosorbide dinitrate has specific indications in HFrEF management, particularly for African American patients or those who cannot tolerate ACE inhibitors or ARBs.

Hydralazine-Nitrate Combination Therapy in HFrEF

Primary Indications (Class I Recommendations):

• For African American patients: The combination of hydralazine and isosorbide dinitrate is recommended for self-described African Americans with moderate-severe symptoms (NYHA class III-IV) who are already on optimal therapy with ACE inhibitors, beta blockers, and diuretics 1
• This recommendation is based on evidence showing significant mortality benefit in this population

Secondary Indications (Class IIa/IIb Recommendations):

• For patients with persistent symptoms: The addition of hydralazine and nitrate combination is reasonable for patients with reduced LVEF who remain symptomatic despite being on an ACE inhibitor and beta blocker 1
• For patients who cannot tolerate ACE inhibitors or ARBs: The combination might be reasonable in patients with HFrEF who cannot take ACE inhibitors or ARBs due to drug intolerance, hypotension, or renal insufficiency 1

Guideline-Directed Medical Therapy (GDMT) Algorithm for HFrEF

First-Line Therapies (before considering hydralazine):

1. ACE inhibitor/ARB/ARNi
2. Beta blocker
3. Mineralocorticoid receptor antagonist (MRA)
4. SGLT2 inhibitor

When to Consider Hydralazine-Nitrate Combination:

• After optimizing the above therapies
• Specifically for African American patients with persistent symptoms
• As an alternative for patients who cannot tolerate ACE inhibitors/ARBs

Important Considerations and Monitoring

Efficacy:

• The combination of hydralazine and isosorbide dinitrate was the first treatment to show improved survival in HFrEF patients in the V-HeFT trial 2
• In African American patients, the A-HeFT trial demonstrated a 43% risk reduction when added to standard therapy 2

Limitations:

• Hydralazine alone has not been shown to improve mortality in HFrEF 3
• The hydralazine-nitrate combination appears inferior to ACE inhibitors on direct comparison 3
• Nitrates alone showed a trend toward harm in some studies 3

Practical Implementation:

• In resistant hypertension management algorithms, hydralazine is considered a step 5 agent, after optimizing diuretics, RAS blockers, calcium channel blockers, beta blockers, and MRAs 1
• The combination therapy is often underutilized in clinical practice due to side effects and polypharmacy concerns 4

Caveats and Pitfalls

• Do not use hydralazine alone for HFrEF management - it must be combined with nitrates for mortality benefit
• Do not substitute hydralazine-nitrate combination for first-line therapies (ACE inhibitors/ARBs, beta blockers, MRAs) unless there are specific contraindications
• Monitor for side effects including headache, dizziness, and lupus-like syndrome with long-term hydralazine use
• Be aware of dosing complexity - the combination typically requires multiple daily doses, which may affect adherence

By following these evidence-based recommendations, hydralazine can be appropriately incorporated into HFrEF management for specific patient populations while maximizing benefits and minimizing risks.