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 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 approach:
| 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 RV 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)
Treatment Algorithm
Low to Intermediate Risk Patients (WHO FC I-III)
Initial Combination Therapy:
- Ambrisentan (ERA) + Tadalafil (PDE5i) is the preferred combination 1
- Alternative combinations include other ERAs (bosentan, macitentan) with PDE5i (sildenafil)
If Monotherapy is Chosen:
- ERA options: Bosentan (62.5 mg BID for 4 weeks, then 125 mg BID), Ambrisentan (5-10 mg daily), or Macitentan (10 mg daily)
- PDE5i options: Sildenafil (20 mg TID) or Tadalafil (40 mg daily)
- Soluble guanylate cyclase stimulator: Riociguat (0.5-1.0 mg TID, titrated to maximum 2.5 mg TID)
- Important: Never combine riociguat with PDE5i due to risk of severe hypotension 1
Inadequate Response to Initial Therapy:
- Add a second class of PAH therapy if on monotherapy
- Add a third class if on dual therapy with inadequate response
High Risk Patients (WHO FC IV)
First-line Therapy:
Combination Therapy:
- Add oral ERA and PDE5i to parenteral prostanoid therapy
Specific Medication Classes
Prostacyclin Derivatives
- Epoprostenol (IV): Start at 2 ng/kg/min, increase by 2 ng/kg/min every 15 minutes until dose-limiting effects or tolerance established 2
- Iloprost (inhaled): 2.5-5.0 μg, 6-9 inhalations/day
- Treprostinil: Available as oral, inhaled, subcutaneous, or IV formulations
Endothelin Receptor Antagonists
- Bosentan: 125 mg BID
- Ambrisentan: 5-10 mg once daily
- Macitentan: 10 mg once daily
Phosphodiesterase-5 Inhibitors
- Sildenafil: 20 mg TID
- Tadalafil: 40 mg once daily
Soluble Guanylate Cyclase Stimulator
- Riociguat: 0.5-1.0 mg TID, titrated to maximum 2.5 mg TID
Prostacyclin Receptor Agonist
- Selexipag: Start at 200 mg BID, titrate to maximum 1,600 mg BID as tolerated
Supportive Care and Lifestyle Modifications
- Supplemental oxygen to maintain saturations >91%
- Supervised exercise training for deconditioned patients
- Immunizations against influenza and pneumococcal pneumonia
- Avoid high altitude exposure
- Avoid pregnancy due to high mortality risk
- Incorporate palliative care services for symptom management
Surgical Options
- Pulmonary endarterectomy: Treatment of choice for eligible CTEPH patients
- Lung transplantation: Consider for patients with inadequate response to maximal medical therapy
- Atrial septostomy: May be considered as a bridge to transplantation
Anticoagulation
- Warfarin is recommended for idiopathic PAH patients and those with indwelling catheters
- Consider on individual basis for connective tissue disease-associated PAH
Follow-up and Monitoring
- Regular assessments every 3-6 months including:
- WHO functional class
- 6-minute walk distance
- BNP/NT-proBNP levels
- Echocardiography
Important Considerations
- Management should occur at specialized centers with expertise in pulmonary hypertension
- Treatment goals include improving symptoms, quality of life, and survival
- Abrupt withdrawal of PAH therapy should be avoided due to risk of clinical deterioration
- Continuous IV prostacyclin requires careful management of the central venous catheter to prevent infection and thrombosis