Treatment of Pulmonary Hypertension
The treatment of pulmonary hypertension requires a targeted approach based on PH classification, with combination therapy of endothelin receptor antagonists (ERAs) and phosphodiesterase-5 inhibitors (PDE-5i) recommended as initial therapy for most patients with pulmonary arterial hypertension (PAH). 1
Classification and Risk Assessment
Before initiating treatment, it's crucial to determine the specific type of pulmonary hypertension:
- Group 1: Pulmonary Arterial Hypertension (PAH)
- 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 1
Risk stratification is essential for treatment decisions:
| Risk Category | 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 |
Treatment Approach for PAH (Group 1)
Initial Therapy
First-line therapy: Initial combination therapy targeting multiple pathways:
For high-risk or WHO FC IV patients: IV epoprostenol is recommended as first-line therapy
For patients unable to tolerate combination therapy: Monotherapy options include:
Medication Dosing and Administration
- Sildenafil: Oral medication for PAH, typically dosed three times daily 3
- Selexipag:
- Starting dose: 200 mcg twice daily
- Increase in increments of 200 mcg twice daily (usually weekly)
- Maximum dose: 1,600 mcg twice daily
- Take with food to improve tolerability 4
- Epoprostenol: IV administration for severe PAH (WHO FC III-IV) 2
Treatment Escalation
- Assess treatment response every 3-6 months
- If treatment goals not met (low-risk status, WHO FC II, 6MWD >440m), consider therapy escalation 1
- Add additional agents from different drug classes for inadequate response to dual therapy
Supportive Care
- Oxygen therapy: Maintain O₂ saturations >91%, especially during air travel or altitude exposure 1
- Diuretics: For right ventricular failure with fluid retention 1
- Anticoagulation: Consider for selected PAH patients
- Immunizations: Recommend influenza and pneumococcal pneumonia vaccines 1
- Supervised exercise training: Beneficial for deconditioned patients 1
Special Considerations
- Pregnancy: Should be avoided due to high maternal and fetal mortality risk (30-50%) 1
- Effective contraception: Strongly recommended for women with PAH 1
- Surgery: Epidural anesthesia preferred over general anesthesia when elective surgery is needed 1
- Hepatic impairment:
- Mild impairment: No dose adjustment needed for selexipag
- Moderate impairment: Start selexipag at 200 mcg once daily
- Severe impairment: Avoid selexipag 4
Surgical Options
- Pulmonary endarterectomy (PEA): Treatment of choice for eligible CTEPH patients 1
- Balloon pulmonary angioplasty (BPA): For inoperable CTEPH or persistent/recurrent PH after PEA 1
- Lung transplantation: For patients with inadequate response to maximal medical therapy 1
- Atrial septostomy: Reserved for patients refractory to medical therapy 5
When to Refer to Specialized Centers
Consider referral to specialized PH centers for:
- Inadequate response to maximal medical therapy
- Need for complex combination therapy
- High-risk features
- Consideration for surgical options 1
Common Pitfalls to Avoid
- Misclassification: Treating all forms of PH with PAH-specific medications
- Delayed escalation: Failing to escalate therapy when treatment goals aren't met
- Fluid management errors: Excessive fluid administration or rapid diuresis in right heart failure
- Medication interactions: Selexipag requires dose reduction when co-administered with moderate CYP2C8 inhibitors 4
- Missing supportive care: Neglecting oxygen therapy, vaccinations, and exercise recommendations