What is the recommended use and dosage of Bidil (isosorbide dinitrate and hydralazine hydrochloride) for heart failure in self-identified black patients?

BiDil (Isosorbide Dinitrate and Hydralazine Hydrochloride) for Heart Failure in Self-Identified Black Patients

BiDil (fixed-dose combination of isosorbide dinitrate and hydralazine) is strongly recommended for self-identified Black patients with NYHA class III-IV heart failure with reduced ejection fraction (HFrEF) who are already receiving optimal therapy with ACE inhibitors/ARBs/ARNIs and beta-blockers, as it significantly reduces morbidity and mortality in this population. 1

Indications and Patient Selection

• BiDil is specifically indicated for:
  • Self-identified Black/African American patients
  • NYHA class III-IV heart failure symptoms
  • Current or prior LVEF ≤40%
  • Patients already receiving standard heart failure therapy (ACE inhibitors, ARBs, or ARNIs plus beta-blockers)

Dosing Recommendations

• Fixed-dose combination tablet containing:
  • Isosorbide dinitrate 20 mg
  • Hydralazine hydrochloride 37.5 mg
• Recommended dosing: One tablet three times daily 2, 3
• Titration may be needed based on patient tolerance, particularly regarding headache and hypotension

Clinical Benefits

BiDil therapy in the target population has demonstrated:

• 43% reduction in overall mortality 2, 4
• 39% reduction in first hospitalization for heart failure 4
• 34% reduction in all recurrent heart failure hospitalizations 5
• 25% reduction in all-cause hospitalizations 5
• Improved left ventricular remodeling:
  • Increased ejection fraction by 2.8 EF units (vs 0.8 in placebo) 6
  • Decreased LV mass index by 7.4 g/m² 6
  • Reduced LV diastolic diameter by 2.2 mm 6
  • Decreased plasma BNP levels by 39 pg/mL (vs 8 pg/mL with placebo) 6

Mechanism of Action

BiDil combines two complementary mechanisms:

• Isosorbide dinitrate: Organic nitrate biotransformed to nitric oxide, a potent vasodilator
• Hydralazine: Provides arterial vasodilation and antioxidant properties that:
  1. Address biochemical alterations in failing cardiovascular system
  2. Prevent nitrate tolerance
  3. Favorably influence nitroso-redox balance 2

This combination is particularly beneficial for Black patients who may have a reduced ability to produce endogenous nitric oxide 3.

Monitoring and Adverse Effects

Common adverse effects to monitor for:

• Headache (49.5% vs 21.1% with placebo) - most common side effect
• Dizziness (30.1% vs 13.7%)
• Hypotension (7.9% vs 4.4%)
• Nausea/vomiting (9.7% vs 6.1%)
• Tachycardia (4.1% vs 2.7%) 3

Important Clinical Considerations

• BiDil should be initiated within a 12-month period of outpatient visits or hospital discharge for heart failure 1
• The combination must specifically be isosorbide dinitrate with hydralazine - other nitrate formulations do not meet guideline requirements 1
• Documentation of medical or patient-specific reasons for not prescribing BiDil should be included if therapy is contraindicated 1

Common Pitfalls to Avoid

1. Failure to identify eligible Black patients with moderate-to-severe heart failure symptoms
2. Suboptimal use of BiDil in eligible patients (utilization has historically been suboptimal) 1
3. Using other nitrate formulations instead of the specific isosorbide dinitrate/hydralazine combination
4. Not monitoring for common side effects, particularly headache and hypotension
5. Failing to recognize that BiDil should be added to, not replace, standard heart failure therapy

BiDil represents an important adjunctive therapy for self-identified Black patients with moderate to severe heart failure who remain symptomatic despite standard therapy, with robust evidence showing significant improvements in mortality, hospitalizations, and cardiac remodeling 1, 2.