What is the recommended treatment for pulmonary hypertension?

Treatment of Pulmonary Hypertension

The recommended treatment for pulmonary hypertension depends on the specific classification, with targeted therapies for pulmonary arterial hypertension (PAH) including initial combination therapy with 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

Classification and Diagnosis

Before initiating treatment, proper classification of pulmonary hypertension is essential:

• Pulmonary hypertension is defined as mean pulmonary artery pressure ≥25 mmHg 2, 1

• Five main groups are recognized 3:

  • Group 1: Pulmonary arterial hypertension (PAH)
  • Group 2: PH due to left heart disease
  • Group 3: PH due to lung diseases
  • Group 4: Chronic thromboembolic pulmonary hypertension (CTEPH)
  • Group 5: PH with unclear/multifactorial mechanisms

• Diagnosis requires right heart catheterization to confirm 1

• Risk assessment should classify patients as low, intermediate, or high risk based on:

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

Treatment Algorithm by PH Classification

Group 1: Pulmonary Arterial Hypertension (PAH)

1. Low/Intermediate Risk Patients:

   • Initial combination therapy with:
     • Endothelin receptor antagonist (ERA): Bosentan (125 mg twice daily), Ambrisentan (5-10 mg once daily), or Macitentan (10 mg once daily)
     • PLUS
     • PDE-5 inhibitor: Sildenafil (20 mg three times daily) 4 or Tadalafil (40 mg once daily) 1

2. High Risk Patients:

   • Parenteral prostacyclin analogs:
     • Epoprostenol IV (indicated to improve exercise capacity) 5
     • Treprostinil SC/IV (indicated to diminish symptoms associated with exercise) 6

3. Supportive Therapies:

   • Diuretics for right ventricular failure with fluid retention
   • Oxygen therapy when arterial blood oxygen pressure is <60 mmHg
   • Anticoagulation for IPAH, heritable PAH, and PAH due to anorexigens
   • Immunization against influenza and pneumococcal infection 1

Group 4: Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

1. Primary Treatment:

   • Pulmonary endarterectomy (PEA) is the treatment of choice and potentially curative 2, 1
   • Lifelong anticoagulation with vitamin K antagonists (target INR 2.0-3.0) 2

2. For Inoperable CTEPH or Residual PH after PEA:

   • PAH-specific medications may be considered 2

Groups 2,3, and 5

• Optimal treatment of the underlying condition is the primary approach 2
• PAH-specific medications are not recommended for PH due to left heart disease or lung disease 2

Important Considerations

• Treatment should be managed at specialized centers with expertise in PH management 1
• Regular monitoring every 3-6 months including WHO functional class, 6-minute walk distance, BNP/NT-proBNP levels, and echocardiography 1
• Avoid abrupt treatment interruption due to risk of severe clinical deterioration 1, 6
• Pregnancy is contraindicated in PAH patients due to high mortality risk (30-50%) 1
• Drug interactions are common, particularly with bosentan, which can interact with warfarin, sildenafil, and cyclosporine 1, 7

Special Situations

• Transition from epoprostenol: Treprostinil is indicated to diminish the rate of clinical deterioration when transitioning from epoprostenol 6
• Hepatic insufficiency: Decrease initial dose of treprostinil in patients with mild or moderate hepatic insufficiency 6
• Calcium channel blockers: Should not be used empirically without demonstrating acute vasoreactivity 1
• Lung transplantation: Consider for patients with inadequate response to maximal medical therapy 1

By following this treatment algorithm based on proper classification and risk assessment, pulmonary hypertension can be managed effectively to improve symptoms, exercise capacity, and potentially survival.