What pulmonary vasodilators are used to treat Eisenmenger syndrome?

Pulmonary Vasodilators for Eisenmenger Syndrome

Bosentan and PDE-5 inhibitors (sildenafil, tadalafil) are the primary pulmonary vasodilators recommended for the treatment of Eisenmenger syndrome, with bosentan having the strongest evidence as first-line therapy. 1

First-Line Therapy

Endothelin Receptor Antagonists (ERAs)

• Bosentan:
  • Most extensively studied and recommended as first-line therapy
  • Dosing: Start at 62.5 mg twice daily for 4 weeks, then increase to 125 mg twice daily if well tolerated 1
  • Demonstrated benefits in a randomized controlled trial (BREATHE-5):
    • Reduces pulmonary vascular resistance
    • Decreases mean pulmonary arterial pressure
    • Increases exercise capacity
    • Does not worsen oxygen saturation 1
  • Long-term benefits confirmed in open-label extension studies 1
  • Monitoring requirements:
    • Monthly liver function tests (dose-dependent hepatotoxicity risk)
    • Quarterly hematocrit checks 1

Second-Line/Alternative Therapy

Phosphodiesterase-5 (PDE-5) Inhibitors

• Sildenafil and Tadalafil:
  • Reasonable alternatives with good evidence for efficacy 1
  • Benefits include:
    • Improved functional capacity
    • Enhanced hemodynamics
    • Better ventilatory efficiency during exercise 2, 3
  • Generally well-tolerated with fewer monitoring requirements than ERAs
  • Particularly useful when ERAs are contraindicated or not tolerated

Combination Therapy

• Bosentan + PDE-5 inhibitor combination:
  • Reasonable approach when symptomatic improvement does not occur with monotherapy 1
  • Demonstrated improvement in:
    • Systemic arterial oxygen saturation
    • 6-minute walk distance
    • Hemodynamic parameters 1, 4

Patient Selection and Monitoring

Patient Assessment

• Confirm diagnosis with cardiac catheterization to assess pulmonary vascular hemodynamics 1
• Exclude other potential contributors to right-to-left shunting:
  • Thromboembolic disease
  • Subpulmonary chamber outflow obstruction
  • Abnormalities of subpulmonary chamber compliance
  • Vascular streaming 1

Monitoring Parameters

• Regular assessment (every 3-6 months) of:
  • WHO functional class
  • 6-minute walk test
  • Pulse oximetry at each visit
  • Echocardiography every 12 months 1
  • BNP levels 1

Important Considerations and Caveats

• Contraindications:

  • Calcium channel blockers should be avoided in Eisenmenger syndrome 1
  • Bosentan is potentially teratogenic - effective contraception is essential 1
  • Hormonal contraceptives may be less effective with bosentan - barrier methods recommended 1

• Adverse effects to monitor:

  • Bosentan: Hepatotoxicity (5-14% depending on dose), anemia, edema 1
  • Male patients should be counseled about potential testicular effects and fertility concerns with ERAs 1

• Treatment goals:

  • Improvement in WHO functional class
  • Increased exercise capacity (6-minute walk distance)
  • Enhanced quality of life
  • Reduced pulmonary vascular resistance
  • Improved survival 4

While both bosentan and PDE-5 inhibitors have shown efficacy, the strongest evidence supports bosentan as first-line therapy for Eisenmenger syndrome, with PDE-5 inhibitors as reasonable alternatives or add-on therapy when response to monotherapy is inadequate.