What is the recommended treatment for pulmonary hypertension?

Treatment of Pulmonary Hypertension

Initial therapy for pulmonary hypertension should consist of combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 inhibitor (PDE-5i) for low/intermediate risk patients, while high-risk patients should receive intravenous prostacyclin analogs such as Epoprostenol. 1

Risk Assessment and Treatment Algorithm

Treatment decisions should be guided by risk stratification:

Risk Assessment Parameters

• WHO functional class
• 6-minute walk distance
• Right ventricular function
• BNP/NT-proBNP levels 1

Risk Categories and Initial Treatment

1. Low Risk (<5% 1-year mortality)

   • WHO FC I-II, 6MWD >440m, No RV dysfunction
   • Treatment: Initial combination therapy with ERA + PDE-5i

2. Intermediate Risk (5-10% 1-year mortality)

   • WHO FC III, 6MWD 165-440m, Moderate RV dysfunction
   • Treatment: Initial combination therapy with ERA + PDE-5i

3. High Risk (>10% 1-year mortality)

   • WHO FC IV, 6MWD <165m, Severe RV dysfunction
   • Treatment: Intravenous prostacyclin analogs (Epoprostenol) 1

Specific Medication Options

Endothelin Receptor Antagonists (ERAs)

• Bosentan (125 mg twice daily)
• Ambrisentan (5 or 10 mg once daily)
• Macitentan (10 mg once daily) 1

Bosentan has been shown to improve exercise capacity, with a mean improvement in six-minute walking distance of 44m compared to placebo, as well as improvements in dyspnea and WHO functional class 2.

Phosphodiesterase-5 Inhibitors (PDE-5i)

• Sildenafil (20 mg three times daily)
• Tadalafil (40 mg once daily) 1

Prostacyclin Analogs

• Epoprostenol (IV) - first drug shown to improve symptoms and survival in PAH 3
• Treprostinil (subcutaneous)
• Iloprost (inhaled) 3

Supportive Therapy

• Diuretics: Recommended for patients with right ventricular failure and fluid retention 1
• Oxygen therapy: Recommended when arterial blood oxygen pressure is consistently <60 mmHg 1
• Anticoagulation: Consider for patients with idiopathic PAH, heritable PAH, and PAH due to anorexigens (target INR 2.0-3.0) 1
• Immunizations: Influenza and pneumococcal vaccines recommended 1

Ongoing Management

• Systematic assessment of clinical response every 3-6 months 1
• Adjust therapy based on response and risk reassessment
• Avoid abrupt treatment interruption due to risk of severe clinical deterioration 1

Advanced Therapies for Refractory Cases

• Lung transplantation: For patients with inadequate response to maximal medical therapy 1
• Atrial septostomy: For refractory patients 1
• Consider referral for mechanical support with right ventricular assist device or extracorporeal membrane oxygenation in acute decompensation 4

Important Medication Considerations

Drug Interactions

• Bosentan + sildenafil: May decrease sildenafil levels by 50% 1
• PDE-5i + nitrates: Contraindicated due to risk of profound hypotension 1
• Bosentan + cyclosporine: Contraindicated due to increased bosentan concentrations 5
• Bosentan + glibenclamide: Not recommended due to increased risk of aminotransferase elevations 5

Monitoring

• Liver function: Monitor for hepatotoxicity, especially with ERAs 5
• Hemoglobin: Monitor for anemia with bosentan 5

Specialized Care

Treatment should be managed at specialized centers with expertise in pulmonary arterial hypertension, with a multidisciplinary team including:

• Consultant physicians with dedicated PH clinical sessions
• Clinical nurse specialists with PH expertise
• Radiologists with expertise in PH imaging
• Cardiologists/PH physicians with expertise in echocardiography and right heart catheterization 1

Special Considerations

• Surgery: Patients with PAH are at increased risk during elective surgeries and require careful perioperative management 1
• High altitude/air travel: Avoid high-altitude exposure and ensure supplemental oxygen during air travel 1
• Pregnancy: Contraindicated due to 30-50% mortality risk 1

Pitfalls to Avoid

• Fluid management: Careful volume management is critical, especially in right ventricular failure; excessive fluid can worsen right ventricular function 4
• Vasopressors vs. fluid boluses: In shock, vasopressors and inotropes are often preferred over fluid boluses to avoid exacerbating right ventricular ischemia 4
• Intubation: Avoid if possible as it may worsen right ventricular function through changes in intrathoracic pressure, hypoxemia, and hypercapnia 4
• Delayed referral: Early consultation with a pulmonary hypertension specialist is advised for optimal management 4