Can we use avaptadil (generic name: avaptadil) for conditions like Acute Respiratory Distress Syndrome (ARDS) or Pulmonary Arterial Hypertension (PAH)?

Aviptadil Use in Pulmonary Arterial Hypertension and ARDS

Aviptadil is not recommended for the treatment of Pulmonary Arterial Hypertension (PAH) or Acute Respiratory Distress Syndrome (ARDS) as it is not included in any current treatment guidelines and lacks sufficient evidence supporting its efficacy for these conditions.

Current Evidence for Aviptadil

Aviptadil (synthetic vasoactive intestinal peptide) has been primarily investigated for COVID-19-related respiratory failure, not for PAH or non-COVID ARDS:

• In the TESICO trial (2023), aviptadil did not significantly improve clinical outcomes up to day 90 compared to placebo in patients with COVID-19-associated acute hypoxemic respiratory failure 1
• Another study (2022) showed that while aviptadil did not meet its primary endpoint for COVID-19 respiratory failure, it demonstrated some improvement in survival at day 60 2

Established Treatments for PAH

Current guidelines for PAH management recommend several well-established medication classes:

First-Line Therapies

• Calcium channel blockers (CCBs): For vasoreactive patients identified through acute vasoreactivity testing 3, 4
  • Options include nifedipine (120-240 mg daily), diltiazem (240-720 mg daily), or amlodipine (up to 20 mg daily)
  • Only approximately 10% of IPAH patients are vasoreactive and respond to CCBs

Standard Therapies for Non-Vasoreactive PAH

1. Endothelin receptor antagonists (ERAs):

   • Bosentan (125 mg twice daily)
   • Ambrisentan (5-10 mg daily)
   • Macitentan (10 mg daily) 3, 4

2. Phosphodiesterase-5 inhibitors (PDE5Is):

   • Sildenafil (20 mg three times daily)
   • Tadalafil (40 mg daily) 3, 4

3. Soluble guanylate cyclase stimulator:

   • Riociguat (0.5-2.5 mg three times daily) 3, 4

4. Prostacyclin pathway agents:

   • Epoprostenol (IV)
   • Treprostinil (IV, subcutaneous, inhaled)
   • Iloprost (inhaled)
   • Selexipag (oral) 3, 4

Combination Therapy Approach

• Initial combination therapy with an ERA (ambrisentan) and PDE5I (tadalafil) is recommended for treatment-naïve PAH patients with WHO FC II and III symptoms 3, 4
• Sequential combination therapy is recommended for patients who fail to respond adequately to monotherapy 3

Treatment for ARDS

For ARDS, current management focuses on:

• Lung-protective ventilation strategies
• Prone positioning to improve oxygenation 5
• Conservative fluid management
• Treatment of underlying causes

No specific pharmacologic agents have shown consistent benefit for ARDS treatment. Studies of inhaled prostacyclins like iloprost have shown some hemodynamic benefits but inconsistent effects on oxygenation and survival 5, 6.

Important Considerations

1. Risk Stratification: Treatment decisions for PAH should be based on comprehensive risk assessment using WHO functional class, exercise capacity, and hemodynamic parameters 4

2. Specialized Care: PAH patients should be managed at centers with expertise in PAH diagnosis and treatment 3, 4

3. Monitoring: Regular assessment of treatment response is essential, with adjustments based on clinical status 3

4. Pregnancy Avoidance: Pregnancy should be avoided in PAH patients due to high mortality risk (30-50%) 4

Conclusion

While aviptadil has been studied in COVID-19-related respiratory failure, there is insufficient evidence to support its use in PAH or non-COVID ARDS. Treatment should follow established guidelines using medications with proven efficacy for these conditions.