What is the recommended treatment for pulmonary hypertension?

Treatment for Pulmonary Arterial Hypertension (PAH)

The recommended treatment for pulmonary arterial hypertension includes risk stratification followed by initial oral combination therapy with an endothelin receptor antagonist (ERA) plus a phosphodiesterase-5 (PDE-5) inhibitor, with preferred combinations being ambrisentan + tadalafil or bosentan + sildenafil. 1

Risk Assessment and Treatment Approach

Risk assessment is essential for guiding treatment decisions in PAH and should include:

• Clinical evaluation for signs of right ventricular failure
• WHO Functional Class (I-IV)
• 6-minute walk distance (6MWD)
• BNP/NT-proBNP levels
• Echocardiographic findings
• Hemodynamic parameters

Risk categories that guide therapy:

Risk Category	Estimated 1-year Mortality	Key Features
Low risk	<5%	WHO FC I-II, 6MWD >440m, No RV dysfunction
Intermediate risk	5-10%	WHO FC III, 6MWD 165-440m, Moderate RV dysfunction
High risk	>10%	WHO FC IV, 6MWD <165m, Severe RV dysfunction

Initial Treatment Algorithm

1. Low/Intermediate Risk Patients (WHO FC II-III):

   • Initial oral combination therapy with ERA + PDE-5 inhibitor 1
   • Preferred combinations:
     • Ambrisentan + Tadalafil
     • Bosentan + Sildenafil

2. High Risk Patients (WHO FC IV):

   • IV epoprostenol is recommended as first-line therapy 1, 2
   • Alternative options include IV treprostinil
   • Consider adding ERA and/or PDE-5 inhibitor for combination therapy

Specific Medication Options

Endothelin Receptor Antagonists (ERAs)

• Bosentan: Improves exercise capacity and delays clinical worsening 3

  • Requires monthly liver function tests due to 3-5% risk of abnormalities
  • Starting dose: 62.5 mg twice daily for 4 weeks, then 125 mg twice daily

• Ambrisentan: Lower incidence of liver abnormalities compared to bosentan 1

  • Improves exercise capacity and delays clinical worsening

• Macitentan: Newer ERA with improved efficacy profile 1

PDE-5 Inhibitors

• Sildenafil: Improves exercise capacity and hemodynamics 4

  • Recommended dose: 20 mg three times daily
  • Side effects: headache, flushing, epistaxis, hypotension

• Tadalafil: Once-daily dosing option 1

Prostacyclin Pathway Medications

• Epoprostenol (IV): First-line therapy for high-risk patients 2

  • Improves exercise capacity, symptoms, and survival
  • Requires continuous IV infusion via central venous catheter

• Treprostinil: Available in IV, subcutaneous, and inhaled forms 1

  • Improves exercise capacity and hemodynamics

• Selexipag: Oral prostacyclin receptor agonist 1

Soluble Guanylate Cyclase Stimulator

• Riociguat: Effective as both monotherapy and combination therapy 1
  • Side effects include hypotension, headache, and dizziness

Supportive Care Measures

1. Diuretic treatment: Indicated for patients with signs of right ventricular failure and fluid retention 5

2. Oxygen therapy: Recommended for patients with:

   • WHO FC III-IV
   • Arterial blood O₂ pressure consistently <60 mmHg 5, 1

3. Oral anticoagulation:

   • Should be considered in patients with idiopathic PAH, heritable PAH, and PAH due to anorexigens 5
   • May be considered in patients with associated PAH (APAH) 5

4. Exercise rehabilitation:

   • Supervised exercise rehabilitation for physically deconditioned patients 5, 1
   • Avoid excessive physical activity that leads to distressing symptoms 5

5. Preventive care:

   • Immunization against influenza and pneumococcal infection 5, 1
   • Effective contraception for women with PAH (pregnancy carries 30-50% mortality risk) 1
   • Epidural anesthesia instead of general anesthesia for elective surgery 5

Follow-up and Treatment Escalation

• Reassess patients every 3-6 months 5, 1
• If treatment goals not achieved:
  • Add inhaled prostanoid
  • Consider IV prostacyclin therapy
  • Refer to specialized centers for patients with inadequate response to maximal medical therapy 1
• Consider lung transplantation for patients with inadequate clinical response to maximal therapy 1

Common Pitfalls to Avoid

• Using calcium channel blockers without vasoreactivity testing can worsen hemodynamics 1
• Excessive fluid administration can worsen right heart failure 1
• Delayed escalation of therapy leads to poor outcomes 1
• Using monotherapy for high-risk patients instead of combination therapy 1
• Failure to refer to specialized pulmonary hypertension centers 1

PAH management requires a multidisciplinary approach at specialized centers with expertise in pulmonary hypertension to optimize outcomes and improve survival.