What is the treatment approach for pulmonary hypertension?

Treatment Approach for Pulmonary Hypertension

The treatment of pulmonary arterial hypertension (PAH) requires risk stratification followed by initial 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. 1

Risk Assessment and Classification

Risk assessment is essential before initiating therapy and should be based on:

• WHO functional class (FC)
• Exercise capacity (6-minute walk distance)
• Right ventricular function
• BNP/NT-proBNP levels 1

Risk categories with estimated 1-year mortality:

• 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 1, 2

Treatment Algorithm

Initial Therapy Based on Risk Assessment:

1. Low/Intermediate Risk Patients:

   • Initial combination therapy with an ERA and PDE-5i 1, 3
   • Recommended ERAs: Bosentan (125 mg twice daily), Ambrisentan (5-10 mg once daily), or Macitentan (10 mg once daily)
   • Recommended PDE-5is: Sildenafil (20 mg three times daily) or Tadalafil (40 mg once daily) 1

2. High Risk Patients:

   • Intravenous prostacyclin analogs (e.g., Epoprostenol) 1, 3
   • Starting dose: 2 ng/kg/min, increased in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting effects occur 4
   • Administered by continuous IV infusion via central venous catheter using an ambulatory pump 4

Follow-up and Treatment Escalation:

• Systematic assessment of clinical response at 3-6 month intervals 3
• If low-risk status is not achieved, escalate to triple combination therapy 3, 1
• For persistent symptoms, increase prostacyclin dose by 1-2 ng/kg/min at intervals of at least 15 minutes 4

Supportive Care

• Diuretics for patients with right ventricular failure and fluid retention 1
• Oxygen therapy when arterial blood oxygen pressure is consistently <60 mmHg 1
• Anticoagulation for IPAH, heritable PAH, and PAH due to anorexigens (target INR 2.0-3.0) 1
• Immunization against influenza and pneumococcal infection 1
• Avoid pregnancy (30-50% mortality risk) 1

Advanced Options for Refractory PAH

• Lung transplantation for patients with inadequate response to maximal medical therapy 3, 1
• Atrial septostomy as a bridge to transplantation for refractory patients 3, 1
• Pulmonary endarterectomy for certain patients, particularly those with CTEPH 1

Important Considerations

• Treatment should be managed at specialized centers with expertise in PAH 3, 1
• Avoid abrupt treatment interruption due to risk of severe clinical deterioration 1
• Be aware of drug interactions:
  • Bosentan may decrease sildenafil levels by 50%
  • PDE-5 inhibitors with nitrates can cause profound hypotension 1

Monitoring and Reassessment

Regular monitoring should include:

• WHO functional class
• Exercise capacity (6MWT)
• Echocardiographic assessment of RV function
• BNP/NT-proBNP levels 1, 2

The goal of therapy is to achieve and maintain low-risk status, which is associated with improved survival rates from 34% in 1991 to more than 60% in 2015 with modern combination therapies 5.