Treatment Recommendations for Pulmonary Hypertension
The recommended treatment for pulmonary hypertension should be based on risk stratification and the specific PH group, with initial combination therapy including an endothelin receptor antagonist (ERA) and a phosphodiesterase-5 inhibitor (PDE5i) for low/intermediate risk patients, while high-risk patients should receive initial combination therapy including intravenous prostacyclin analogues. 1
Classification and Diagnosis
Pulmonary hypertension is classified into five groups:
- 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
Diagnosis requires right heart catheterization showing mean pulmonary artery pressure ≥25 mmHg, with pre-capillary PH defined by pulmonary wedge pressure ≤15 mmHg 2, 1.
Risk Stratification
Treatment decisions should be guided by risk assessment:
| Risk Category | Estimated 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 Algorithm by PH Group
Group 1 (PAH)
Low/Intermediate Risk Patients:
High Risk Patients:
Inadequate Response:
Group 2 (PH due to Left Heart Disease)
- Primary approach: Optimal treatment of the underlying left heart disease 2
- Not recommended: PAH-specific drug therapy 2
Group 3 (PH due to Lung Disease)
- Primary approach: Optimal treatment of the underlying lung disease including long-term O₂ therapy for chronic hypoxemia 2
- Not recommended: PAH-specific drug therapy 2
Group 4 (CTEPH)
- First-line: Surgical pulmonary endarterectomy for eligible patients 2, 1
- Required: Lifelong anticoagulation 2
- Alternative: PAH-specific drug therapy may be indicated for patients not candidates for surgery or with residual PH after pulmonary endarterectomy 2
Medication Details
Endothelin Receptor Antagonists (ERAs)
- Bosentan: Start at 62.5 mg twice daily for 4 weeks, then increase to 125 mg twice daily 1, 5, 6
- Ambrisentan: Recommended in combination with tadalafil 1
- Macitentan: Alternative ERA option 1
- Monitoring: Regular liver function tests due to risk of hepatotoxicity 1
PDE5 Inhibitors
- Sildenafil: 20 mg three times daily 1, 7
- Tadalafil: Effective in combination with ambrisentan 1
- Contraindication: Must not be combined with nitrates due to risk of severe hypotension 1, 7
Prostacyclin Analogues
- IV Epoprostenol: Treatment of choice for high-risk patients 1, 3
- Subcutaneous Treprostinil: Starting dose 1.25 ng/kg/min (0.625 ng/kg/min if not tolerated), with weekly incremental increases 4
- Warning: Avoid abrupt withdrawal which can lead to rebound pulmonary hypertension 1, 4
Monitoring and Follow-up
- Regular assessments every 3-6 months including:
- WHO Functional Class
- 6-minute walk distance
- BNP/NT-proBNP levels
- Echocardiography
- Potentially hemodynamic parameters 1
Special Considerations
- Hepatic insufficiency: Decrease initial dose of treprostinil to 0.625 ng/kg/min; titrate medications slowly 4
- Supraventricular arrhythmias: Treat aggressively as they can lead to clinical deterioration 1
- Pregnancy: Should be avoided due to high mortality risk 1
- Air travel: Ensure supplemental oxygen during air travel to maintain saturations >91% 1
Referral to Specialized Centers
Management should occur at specialized centers with expertise in pulmonary hypertension, particularly for:
- Inadequate response to maximal medical therapy
- Need for complex combination therapy
- High-risk features
- Consideration for surgical options 2, 1
A specialized PH center should follow at least 50 patients with PAH or CTEPH and receive at least two new referrals per month 2.