What are the management options for pulmonary artery hypertension?

Management of Pulmonary Arterial Hypertension

Initial combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 inhibitor (PDE5i) is recommended as first-line treatment for low/intermediate risk pulmonary arterial hypertension (PAH) patients, while high-risk patients should receive initial combination therapy including intravenous prostacyclin analogues. 1

Risk Stratification

Risk assessment is crucial for determining the appropriate treatment strategy:

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

Additional parameters for risk assessment:

• Clinical signs of right ventricular failure
• BNP (<50 ng/L for low risk, 50-300 ng/L for intermediate risk, >300 ng/L for high risk)
• NT-proBNP (<300 ng/L for low risk, 300-1400 ng/L for intermediate risk, >1400 ng/L for high risk) 1

Treatment Algorithm

Low to Intermediate Risk Patients (WHO FC II-III)

1. Initial Combination Therapy:

   • Ambrisentan (ERA) + Tadalafil (PDE5i) is the preferred combination 1
   • Alternative ERAs: Bosentan, Macitentan
   • Alternative PDE5i: Sildenafil

2. Monotherapy Options (if combination therapy not feasible):

   • ERAs: Bosentan (62.5 mg twice daily for 4 weeks, then 125 mg twice daily), Ambrisentan (5-10 mg once daily), or Macitentan (10 mg once daily)
   • PDE5i: Sildenafil (20 mg three times daily) or Tadalafil (40 mg once daily)
   • Soluble guanylate cyclase stimulator: Riociguat (0.5-1.0 mg every 8 hours, titrated to maximum 2.5 mg) 2, 1

   Note: Riociguat must not be combined with PDE5i due to risk of severe hypotension 1

High Risk Patients (WHO FC IV)

1. Initial Parenteral Prostacyclin Therapy:

   • IV epoprostenol is the treatment of choice (starting dose 2 ng/kg/min, titrated based on clinical response) 1, 3
   • Alternative options: IV treprostinil or SC treprostinil 1

2. Combination Therapy:

   • Add ERA and/or PDE5i to prostacyclin therapy 1

Treatment Escalation

For patients with inadequate clinical response to initial therapy:

1. Dual Therapy: Add a second drug class if monotherapy is insufficient
2. Triple Therapy: Add a prostacyclin analogue if dual therapy is insufficient
3. Consider alternative options:
   • Adding inhaled iloprost or treprostinil to oral therapy
   • Transitioning to IV prostacyclin therapy 1

Specific Drug Classes

Prostacyclin Derivatives

• Epoprostenol (IV): Most potent option, improves exercise capacity and survival in NYHA Class III-IV patients 3
• Treprostinil: Available in subcutaneous, IV, inhaled, and oral formulations
• Iloprost: Inhaled formulation 2

Endothelin Receptor Antagonists (ERAs)

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

Phosphodiesterase-5 Inhibitors (PDE5i)

• Sildenafil: 20 mg every 8 hours
• Tadalafil: 40 mg once daily 2

Other Agents

• Riociguat (soluble guanylate cyclase stimulator): 0.5-1.0 mg every 8 hours, titrated up to 2.5 mg
• Selexipag (prostacyclin receptor agonist): Starting at 200 mg twice daily, titrated to maximum 1,600 mg twice daily 2

Supportive Care and Monitoring

• Regular assessments every 3-6 months including WHO functional class, 6-minute walk distance, BNP/NT-proBNP levels, and echocardiography 1
• Oral anticoagulation with warfarin is recommended for idiopathic PAH patients and those with indwelling catheters 1
• Supplemental oxygen for hypoxemia
• Diuretics for fluid retention
• Supervised exercise training for deconditioned patients
• Immunizations against influenza and pneumococcal pneumonia 1

Surgical Options

• Pulmonary endarterectomy: Treatment of choice for eligible chronic thromboembolic pulmonary hypertension (CTEPH) patients 1
• Lung transplantation: Consider for patients with inadequate response to maximal medical therapy 1
• Atrial septostomy: May be considered as a bridge to transplantation 1

Important Considerations

• Management should occur at specialized centers with expertise in pulmonary hypertension 1
• Avoid abrupt withdrawal of PAH therapy as this can lead to clinical deterioration 3
• Patients should avoid high altitude exposure and ensure supplemental oxygen during air travel 1
• Pregnancy carries high mortality risk in PAH patients and should be avoided 1

By following this comprehensive approach to PAH management based on risk stratification, patients can achieve improved exercise capacity, hemodynamics, and potentially survival outcomes.