Is hydrazine a recommended treatment for a patient like Lisa Ryan with heart failure?

Hydralazine in Heart Failure Management

Hydralazine in combination with nitrates is recommended as a third or fourth-line therapy for heart failure, particularly for self-identified African American patients with persistent symptoms despite optimal therapy or for patients who cannot tolerate ACE inhibitors or ARBs due to intolerance, hypotension, or renal insufficiency. 1, 2

Role in Heart Failure Treatment Algorithm

Hydralazine is not a first-line treatment for heart failure. The current guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF) follows a quadruple therapy approach:

1. First-line therapies:

   • ACE inhibitors or ARBs (or ARNI)
   • Beta-blockers
   • Mineralocorticoid receptor antagonists (MRAs)
   • SGLT2 inhibitors

2. When to consider hydralazine with nitrates:

   • For patients who cannot take ACE inhibitors/ARBs due to:
     • Drug intolerance
     • Hypotension
     • Renal insufficiency 2
   • For self-identified African American patients with persistent symptoms despite optimal therapy 2, 1

Evidence Supporting Use

The combination of hydralazine and isosorbide dinitrate has been shown to:

• Decrease preload and afterload
• Reduce left ventricular wall tension
• Improve left ventricular ejection fraction
• Induce left ventricular reverse remodeling
• Provide antioxidant properties and improve NO bioavailability 3

In the African-American Heart Failure Trial (A-HeFT), this combination demonstrated a 43% risk reduction in mortality for Black patients when added to standard therapy 4.

Dosing and Administration

When prescribed, the combination should be titrated to:

• Hydralazine: Starting at lower doses and increasing to target doses as tolerated
• Isosorbide dinitrate: Typically given in combination with hydralazine

Monitoring and Side Effects

Common side effects include:

• Headache
• Dizziness
• Tachycardia
• Hypotension

Side effects are dependent on dose, duration, and acetylator status 5. Regular monitoring of blood pressure and heart rate is essential when initiating and titrating this therapy.

Important Considerations

1. Guideline Classification: The combination is classified as a Class IIb recommendation for patients who cannot take ACE inhibitors/ARBs and Class IIa for African American patients with persistent symptoms despite optimal therapy 2.

2. Limited Evidence: Earlier studies showed mixed results. A 1982 study found no significant difference between hydralazine alone and placebo in chronic heart failure 6, while later studies demonstrated benefits when combined with nitrates.

3. Underutilization: Despite evidence supporting its use in specific populations, this combination remains underutilized, particularly in people of African ancestry in Europe 4.

Conclusion for Lisa Ryan

For a patient like Lisa Ryan, hydralazine would not be a first-line treatment for heart failure. It should only be considered if:

1. She is self-identified as African American AND has persistent symptoms despite optimal therapy with ACE inhibitors/ARBs, beta-blockers, MRAs, and SGLT2 inhibitors, OR
2. She cannot tolerate ACE inhibitors or ARBs due to specific contraindications.

Otherwise, standard quadruple therapy should be optimized before considering hydralazine with nitrates.