What is the recommended treatment for pulmonary arterial hypertension?

Treatment of Pulmonary Arterial Hypertension

The recommended treatment for pulmonary arterial hypertension (PAH) should follow a risk-stratified approach, with initial combination therapy using an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 inhibitor (PDE-5i) for low/intermediate risk patients, and parenteral prostacyclin analogs for high-risk patients. 1

Initial Assessment and Risk Stratification

Before initiating therapy, patients should undergo:

1. Right heart catheterization to confirm PAH diagnosis (defined as mean pulmonary artery pressure ≥25 mmHg with pulmonary capillary wedge pressure ≤15 mmHg) 2, 1
2. Acute vasoreactivity testing to identify potential responders to calcium channel blockers 1
3. Risk assessment based on:
   • WHO functional class
   • 6-minute walk distance
   • Right ventricular function
   • BNP/NT-proBNP levels

Risk Category	Estimated 1-Year Mortality	Key Characteristics
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

Treatment Algorithm

1. Acute Vasoreactive Patients (10-15% of IPAH)

• First-line therapy: High-dose calcium channel blockers 1
• Monitor closely for sustained response

2. Non-vasoreactive Patients with Low/Intermediate Risk

• Initial combination therapy with:
  • Endothelin receptor antagonist (ERA) AND
  • Phosphodiesterase-5 inhibitor (PDE-5i) 1

3. High-Risk Patients

• Initial therapy should include intravenous prostacyclin analogs 1
  • Epoprostenol (IV) - preferred for most severe cases 3, 4
  • Treprostinil (IV, SC, inhaled, or oral) 5

Medication Classes and Dosing

1. Endothelin Receptor Antagonists (ERAs)

• Bosentan: 125 mg twice daily 2, 6
• Ambrisentan: 5 or 10 mg once daily 2
• Macitentan: 10 mg once daily 2, 1

2. Phosphodiesterase-5 Inhibitors (PDE-5i)

• Sildenafil: 20 mg three times daily 2, 1
• Tadalafil: 40 mg once daily 2, 1

3. Soluble Guanylate Cyclase Stimulator

• Riociguat: 0.5-1.0 mg three times daily, titrated to maximum 2.5 mg three times daily 2, 1

4. Prostacyclin Analogs

• Epoprostenol (IV): Initial dose 2 ng/kg/min, increased as tolerated 2, 3
• Treprostinil:
  • IV/SC: Initial dose 1.25 ng/kg/min, titrated based on clinical response 2, 5
  • Inhaled: 18-54 μg (3-9 inhalations) four times daily 2
  • Oral: 0.25 mg twice daily or 0.125 mg three times daily, titrated as tolerated 2

5. Prostacyclin Receptor Agonist

• Selexipag: Initial dose 200 μg twice daily, titrated to maximum 1,600 μg twice daily 2, 1

Supportive Therapy

• Diuretics: For patients with right ventricular failure and fluid retention 2, 1
• Oxygen therapy: When arterial blood oxygen pressure is consistently <8 kPa (60 mmHg) 2, 1
• Anticoagulation: Consider for patients with IPAH, heritable PAH, and PAH due to anorexigens 2, 1
• Immunization: Against influenza and pneumococcal infection 2

Treatment Escalation

If clinical response is inadequate with initial therapy:

1. Add a third drug class (sequential combination therapy)
2. Consider parenteral prostacyclin if not already included
3. Evaluate for lung transplantation in patients with inadequate response to maximal medical therapy 1

Monitoring and Follow-up

Regular evaluations every 3-6 months including:

• WHO functional class
• 6-minute walk distance
• BNP/NT-proBNP levels
• Echocardiography 2, 1

Important Considerations

• Avoid abrupt cessation of PAH therapy due to risk of clinical deterioration 1, 5
• Pregnancy is contraindicated in patients with PAH (30-50% mortality) 2
• Specialized centers with expertise in PAH management should oversee treatment 1
• Drug interactions are common with PAH medications, particularly with bosentan, which can interact with warfarin, sildenafil, and cyclosporine 2, 7

By following this evidence-based approach to PAH treatment, clinicians can optimize outcomes related to morbidity, mortality, and quality of life for patients with this complex condition.