What are the treatment options for pulmonary hypertension (pulmonary HTN)?

Treatment of Pulmonary Hypertension

For patients with pulmonary arterial hypertension (PAH), initial combination therapy with ambrisentan and tadalafil is recommended as first-line treatment for WHO Functional Class II-III patients to improve outcomes and delay clinical deterioration. 1

Classification and Initial Approach

Proper treatment requires accurate classification of pulmonary hypertension (PH) into one of five groups:

• Group 1: Pulmonary Arterial Hypertension (PAH)
• Group 2: PH due to left heart disease
• Group 3: PH due to lung diseases/hypoxia
• Group 4: Chronic thromboembolic PH (CTEPH)
• Group 5: PH with unclear/multifactorial mechanisms

Treatment strategies differ significantly based on classification, with PAH-specific therapies only approved for Group 1 and select Group 4 patients 1, 2.

Treatment Algorithm for PAH (Group 1)

Step 1: Risk Assessment

• Categorize patients into low, intermediate, or high-risk based on:
  • WHO Functional Class (FC)
  • Exercise capacity (6-minute walk distance)
  • RV function
  • BNP/NT-proBNP levels 2

Step 2: Vasoreactivity Testing

• Mandatory for all PAH patients
• Positive response: fall in mean PAP ≥10 mmHg to ≤40 mmHg with unchanged/increased cardiac output 1

Step 3: Initial Therapy Selection

For Vasoreactive Patients:

• Calcium channel blockers (only for those with positive vasoreactivity test) 1, 2

For Non-vasoreactive Patients:

• Low/Intermediate Risk (WHO FC II-III):

  • First choice: Initial combination therapy with ambrisentan and tadalafil 1
  • Alternative: Monotherapy with an endothelin receptor antagonist (ERA), PDE-5 inhibitor, or soluble guanylate cyclase stimulator 1

• High Risk (WHO FC IV):

  • First choice: Initial combination therapy including IV prostacyclin analog (preferably IV epoprostenol) 1, 3
  • IV epoprostenol has demonstrated reduced 3-month mortality in high-risk PAH patients 1

Step 4: Follow-up and Sequential Therapy

• Assess clinical response every 3-6 months 2
• If inadequate response to initial therapy:
  • Add second class of PAH therapy
  • If still inadequate, add third class of PAH therapy 1
  • Consider triple combination therapy for patients with progressive disease 1, 4

Step 5: Advanced Options

• Consider lung transplantation after inadequate clinical response to maximal medical therapy 1
• Balloon atrial septostomy may be considered as a palliative or bridging procedure 1

Specific Medication Classes

Endothelin Receptor Antagonists (ERAs)

• Examples: Bosentan, ambrisentan, macitentan
• Benefits: Improved exercise capacity, hemodynamics, and delayed clinical worsening 5, 6
• Caution: Potential hepatotoxicity and teratogenicity 6

PDE-5 Inhibitors

• Examples: Sildenafil, tadalafil
• Benefits: Improved exercise capacity and hemodynamics 7

Prostacyclin Pathway Agents

• Examples: Epoprostenol (IV), treprostinil (IV, SC, inhaled), iloprost (inhaled)
• Benefits: IV epoprostenol improves survival in severe PAH 3
• Administration: Continuous infusion for IV/SC forms; multiple daily inhalations for inhaled forms 8

Soluble Guanylate Cyclase Stimulators

• Example: Riociguat
• Caution: Contraindicated in combination with PDE-5 inhibitors 1

Important Supportive Measures

• Avoid pregnancy due to high mortality risk 1
• Maintain immunizations against influenza and pneumococcal pneumonia 1
• Avoid non-essential surgery; when necessary, use a multidisciplinary approach 1
• Consider supervised exercise training for deconditioned patients 2
• Provide supplemental oxygen for hypoxemic patients 2

Common Pitfalls to Avoid

• Delayed diagnosis due to non-specific symptoms
• Misclassification of PH group leading to inappropriate treatment
• Failure to refer to specialized centers
• Inadequate follow-up and risk assessment
• Underutilization of combination therapy
• Failure to recognize treatment failure early enough to escalate therapy 2

Special Considerations

• Combination therapy: The AMBITION trial demonstrated superiority of initial combination therapy with ambrisentan and tadalafil over monotherapy in delaying clinical failure 1
• Transition between therapies: When transitioning from epoprostenol to treprostinil, carefully consider risks and benefits 8
• Hepatic insufficiency: Decrease initial dose of treprostinil in patients with mild to moderate hepatic insufficiency 8

Due to the complexity of management, referral to a specialized pulmonary hypertension center is strongly recommended for optimal care 1.