What is the recommended treatment for pulmonary hypertension?

Treatment of Pulmonary Hypertension

The recommended treatment for pulmonary arterial hypertension (PAH) should follow a comprehensive, evidence-based algorithm that includes general supportive measures, vasoreactivity testing, and specific pharmacologic therapy based on disease severity and patient functional class. 1

Initial Assessment and Classification

Before initiating treatment, it's essential to:

• Confirm PAH diagnosis with right heart catheterization (mean pulmonary artery pressure ≥25 mmHg with pulmonary capillary wedge pressure ≤15 mmHg)
• Determine WHO functional class (I-IV)
• Perform vasoreactivity testing to identify potential responders to calcium channel blockers
• Assess risk status (low, intermediate, or high risk) based on clinical, exercise, biochemical, and hemodynamic parameters 1

General Supportive Measures

1. Oxygen therapy

   • Maintain oxygen saturations >91% 1
   • Consider supplemental oxygen during altitude exposure or air travel

2. Anticoagulation

   • Warfarin (INR 2.0-3.0) recommended for patients with idiopathic PAH 1
   • Use caution in patients with liver disease or bleeding risk 1

3. Vaccinations

   • Maintain current immunizations against influenza and pneumococcal pneumonia 1

4. Avoid pregnancy due to high mortality risk

Pharmacologic Therapy Based on Functional Class

Vasoreactive Patients

• Patients who demonstrate positive acute vasoreactivity (defined as a fall in mean PAP of at least 10 mmHg to ≤40 mmHg with increased or unchanged cardiac output) should receive calcium channel blockers 1
• Monitor closely for sustained response (functional class I or II with near-normal hemodynamics)

Non-Vasoreactive Patients

WHO Functional Class II-III:

• First-line options:
  • Endothelin receptor antagonists (e.g., bosentan) 1, 2
  • Phosphodiesterase-5 inhibitors (e.g., sildenafil) 3
  • Consider oral therapy for stable patients

WHO Functional Class III with Rapid Progression or Class IV:

• First-line therapy:
  • Continuous intravenous epoprostenol 4 - the only therapy proven to improve survival in PAH 1
  • Alternative prostanoids:
    • Treprostinil (subcutaneous or intravenous) 5
    • Inhaled iloprost 1

Specific Medication Details

Prostanoids

• Epoprostenol (IV): Improves exercise capacity, hemodynamics, and survival; preferred for critically ill patients 4
• Treprostinil (SC/IV): Indicated for PAH to diminish symptoms associated with exercise; can be used for transition from epoprostenol 5

Endothelin Receptor Antagonists

• Bosentan: Dual endothelin receptor antagonist that improves exercise capacity and hemodynamics 2
  • Requires monthly liver function monitoring
  • Contraindicated with cyclosporine and glibenclamide 6

PDE-5 Inhibitors

• Sildenafil: Improves exercise capacity and hemodynamics 3
  • Contraindicated with nitrates due to risk of severe hypotension
  • Typical dose is 20 mg three times daily

Combination Therapy

For patients who do not achieve treatment goals with monotherapy, combination therapy using medications with different mechanisms of action may be considered 1.

Special Considerations

Porto-pulmonary Hypertension

• Use diuretics to control volume overload and ascites
• Avoid beta-blockers which may worsen PAH
• Consider IV epoprostenol with caution due to risk of increased ascites 1

Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

• Pulmonary endarterectomy is the treatment of choice for operable patients
• Lifelong anticoagulation with vitamin K antagonists (INR 2.0-3.0)
• Medical therapy may be considered for inoperable patients 1

Treatment Algorithm

1. Confirm diagnosis and assess severity
2. Implement general measures (oxygen, anticoagulation, diuretics as needed)
3. Perform vasoreactivity testing
4. If vasoreactive: Start calcium channel blockers and monitor response
5. If non-vasoreactive:
   • WHO FC II-III: Start with oral therapy (endothelin receptor antagonist or PDE-5 inhibitor)
   • WHO FC III (progressive) or IV: Start parenteral prostanoid therapy
6. Reassess response at 3-6 months using a panel of clinical, exercise, biochemical, and hemodynamic parameters 1
7. If inadequate response: Consider combination therapy or lung transplantation

Monitoring and Follow-up

Regular assessment every 3-6 months should include:

• Functional class determination
• Exercise capacity (6-minute walk test)
• Echocardiography
• Basic laboratory tests
• Consider repeat right heart catheterization if clinical deterioration occurs 1

The goal of treatment is to achieve and maintain a low-risk profile, which is associated with improved survival 1.