What is the recommended treatment approach for patients with pulmonary hypertension?

Assessment and Treatment for Pulmonary Hypertension

For patients with pulmonary arterial hypertension (PAH), a comprehensive treatment approach should include risk stratification followed by targeted pharmacotherapy with combination therapy being the preferred strategy for most patients, particularly using endothelin receptor antagonists (ERA) plus phosphodiesterase-5 inhibitors (PDE-5i) as initial therapy for WHO Functional Class II-III patients, and IV epoprostenol for high-risk or WHO Functional Class IV patients. 1

Diagnosis and Risk Stratification

Definition and Classification

• Pulmonary hypertension (PH) is defined as mean pulmonary artery pressure ≥25 mmHg 1
• PAH (Group 1) must be distinguished from other forms of PH:
  • Group 2: PH due to left heart disease
  • Group 3: PH due to lung diseases/hypoxia
  • Group 4: Chronic thromboembolic PH (CTEPH)
  • Group 5: PH with unclear mechanisms 2, 1

Risk Assessment Parameters

• Risk categories based on 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

Treatment Algorithm

Initial Therapy Based on Risk Assessment

Low to Intermediate Risk (WHO FC II-III)

1. Initial Combination Therapy (Preferred) 2, 1

   • ERA + PDE-5i combination:
     • Ambrisentan + Tadalafil (preferred combination) 2, 1
     • Bosentan + Sildenafil (alternative combination) 1

2. Monotherapy Options (if combination not possible)

   • ERAs: Bosentan, Ambrisentan, or Macitentan
   • PDE-5i: Sildenafil or Tadalafil
   • Soluble guanylate cyclase stimulator: Riociguat (not to be combined with PDE-5i) 2, 1

High Risk (WHO FC IV)

1. IV Epoprostenol (First-line) 1, 3

   • Starting dose: 2 ng/kg/min
   • Increase by 2 ng/kg/min every 15 minutes until dose-limiting effects or tolerance established 3
   • Administered via continuous IV infusion through central venous catheter 3

2. Alternative options:

   • IV treprostinil
   • Consider adding ERA and/or PDE-5i for combination therapy 1

Sequential Therapy for Inadequate Response

• For patients who remain symptomatic on initial therapy:
  • If on monotherapy with ERA or PDE-5i, add inhaled prostanoid (iloprost or treprostinil) 2
  • If on PDE-5i or inhaled prostanoid, consider adding macitentan 2
  • For patients on dual therapy who remain symptomatic, add a third class of PAH medication 2

Supportive Measures

General Measures

• Oxygen therapy: Maintain O₂ saturations >91%, especially during air travel or altitude exposure 2, 1
• Immunizations: Maintain current immunizations against influenza and pneumococcal pneumonia 2
• Pregnancy: Should be avoided due to high maternal and fetal mortality risk (30-50%) 2, 1
• Surgery: Avoid non-essential surgery; when necessary, manage at a pulmonary hypertension center 2

Management of Right Heart Failure

• Diuretics: For right ventricular failure with fluid retention
• Avoid excessive fluid administration: Can worsen right heart failure 1
• Avoid rapid diuresis: May lead to hypotension and renal dysfunction 1

Special Considerations

Critical Warnings

• Do not abruptly withdraw or lower dose of PAH medications 3
• Avoid calcium channel blockers without vasoreactivity testing 1
• Riociguat and PDE-5i combination is contraindicated 1
• Monitor hemodynamics carefully when adding or escalating therapies 1

Follow-up and Escalation

• Regular follow-up assessments every 3-6 months 1
• Evaluate treatment response and consider therapy escalation if treatment goals not met 1
• Treatment goal: Achieve low-risk status 1

Referral to Specialized Centers

• Consider referral for patients with:
  • Inadequate response to maximal medical therapy
  • Need for complex combination therapy
  • High-risk features
  • Consideration for surgical options 1

Surgical Options

• Pulmonary endarterectomy: Treatment of choice for eligible CTEPH patients 1
• Balloon pulmonary angioplasty: For inoperable CTEPH 1
• Balloon atrial septostomy: Palliative procedure in select cases 1
• Lung transplantation: Consider for patients with inadequate response to maximal medical therapy 1

PAH treatment requires careful monitoring, appropriate risk stratification, and timely escalation of therapy to improve outcomes. Early referral to specialized centers for complex cases is essential for optimal management.