Does Bidil (isosorbide dinitrate and hydralazine hydrochloride) reduce worsening heart failure?

BiDil Reduces Worsening Heart Failure in Specific Patient Populations

BiDil (isosorbide dinitrate and hydralazine hydrochloride) significantly reduces worsening heart failure in self-identified African American patients with NYHA class III-IV heart failure who remain symptomatic despite optimal standard therapy. 1

Efficacy in Different Patient Populations

African American Patients

• BiDil demonstrated a 43% reduction in overall mortality and 33% reduction in first hospitalization for heart failure in African American patients with advanced heart failure 1
• The combination is specifically recommended as a Class I treatment (highest level of evidence) for self-described African Americans with NYHA class III-IV HFrEF who are already receiving optimal therapy with ACE inhibitors and beta blockers 2
• The benefit is presumed to be related to enhanced nitric oxide bioavailability 2

Non-African American Patients

• Limited evidence exists for efficacy in non-African American populations
• May be considered (Class IIa recommendation) for patients with current or prior symptomatic HFrEF who cannot tolerate ACE inhibitors or ARBs due to:
  • Drug intolerance
  • Hypotension
  • Renal insufficiency 2

Mechanism of Action

BiDil works through dual mechanisms:

1. Isosorbide dinitrate: Acts as a nitric oxide donor, causing venodilation
2. Hydralazine: Functions as both an arterial vasodilator and antioxidant 3

Together, these mechanisms:

• Decrease preload and afterload
• Reduce left ventricular end-diastolic diameter
• Decrease mitral regurgitation volume
• Reduce pulmonary artery pressure
• Improve left ventricular ejection fraction
• Induce left ventricular reverse remodeling 4

Dosing and Administration

When using the fixed-dose combination:

• Initial dose: 1 tablet containing 37.5 mg hydralazine/20 mg isosorbide dinitrate three times daily
• Maximum dose: 2 tablets three times daily (total daily dose: 225 mg hydralazine/120 mg isosorbide dinitrate) 2

Common Side Effects and Precautions

• Headache and dizziness are common side effects
• Gastrointestinal complaints occur frequently
• Poor adherence may result from the large number of tablets required and frequency of administration 2
• Consider slower titration if side effects are problematic

Important Clinical Considerations

• BiDil should not be used as first-line therapy in patients who have not previously tried ACE inhibitors or ARBs 2
• It should not replace ACE inhibitors or ARBs in patients who tolerate these medications without difficulty 2
• Blood pressure effects: Interestingly, BiDil does not reduce systolic blood pressure in patients with already low systolic BP (below 126 mmHg), making it safe even in patients with lower baseline blood pressures 5
• The efficacy of BiDil is maintained regardless of baseline blood pressure, providing benefit even to patients with low systolic blood pressure who typically have more severe heart failure 5

Clinical Algorithm for BiDil Use

1. For African American patients with NYHA class III-IV heart failure:

   • Ensure patient is already on optimal therapy (ACE inhibitors/ARBs, beta blockers, aldosterone antagonists)
   • If still symptomatic, add BiDil

2. For patients intolerant to ACE inhibitors/ARBs:

   • Document specific intolerance (renal dysfunction, hypotension, angioedema)
   • Consider BiDil as an alternative therapy
   • Monitor closely for side effects and titrate slowly

3. For all patients on BiDil:

   • Start with low dose and titrate as tolerated
   • Monitor for headache, dizziness, and gastrointestinal symptoms
   • Assess improvement in heart failure symptoms and functional capacity