What are the treatment guidelines for pulmonary hypertension?

Pulmonary Hypertension Treatment Guidelines

The treatment of pulmonary arterial hypertension (PAH) should follow a risk-stratified approach with the goal of achieving or maintaining a low-risk profile, defined as WHO Functional Class I-II, 6-minute walk distance >440m, and absence of right ventricular failure signs. 1

Initial Assessment and Risk Stratification

Comprehensive evaluation is mandatory before initiating therapy, including: 1

• WHO Functional Class determination - critical for treatment decisions 1
• 6-minute walk test (6MWT) with Borg dyspnea score 1
• BNP or NT-proBNP levels - prognostic marker 1
• Echocardiography - assess right ventricular function, pericardial effusion, TAPSE 1
• Right heart catheterization - essential for definitive diagnosis and baseline hemodynamics 1

Risk stratification divides patients into three categories: 1

• Low risk (<5% 1-year mortality): WHO-FC I-II, 6MWD >440m, BNP <50 ng/L, no RV dysfunction
• Intermediate risk (5-10% 1-year mortality): WHO-FC III, 6MWD 165-440m, moderate RV dysfunction
• High risk (>10% 1-year mortality): WHO-FC III-IV, 6MWD <165m, BNP >300 ng/L, pericardial effusion, severe RV dysfunction

General Measures and Supportive Therapy

Pregnancy must be avoided in all PAH patients (Class I recommendation) 1

Immunization against influenza and pneumococcal infection is recommended (Class I) 1

Diuretic treatment is indicated for patients with signs of RV failure and fluid retention (Class I) 1

Continuous long-term oxygen therapy is indicated when arterial PaO2 is consistently <60 mmHg (8 kPa) (Class I) 1

Oral anticoagulation should be considered for patients with idiopathic PAH, heritable PAH, and PAH due to anorexigens (Class IIa) 1

Supervised exercise rehabilitation should be considered for physically deconditioned patients (Class IIa) 1

PAH-Specific Pharmacotherapy

Treatment Algorithm by Risk Status

For treatment-naive patients with low-intermediate risk (WHO-FC II-III): 1

• Initial oral combination therapy with an endothelin receptor antagonist (ERA) plus a phosphodiesterase-5 inhibitor (PDE-5i) is increasingly preferred
• Monotherapy options include ERAs (bosentan, ambrisentan), PDE-5i (sildenafil, tadalafil), or soluble guanylate cyclase stimulators

For high-risk patients (WHO-FC IV or rapidly progressive disease): 1, 2

• Intravenous epoprostenol is the treatment of choice - established effectiveness in NYHA FC III-IV patients 2
• Initial dosing: Start at 2 ng/kg/min, increase by 2 ng/kg/min increments every ≥15 minutes until dose-limiting effects or tolerance established 2
• Chronic dosing adjustments: Increase by 1-2 ng/kg/min at intervals ≥15 minutes based on clinical response 2
• Administration: Continuous IV infusion via central venous catheter using ambulatory pump 2

Endothelin Receptor Antagonists

Bosentan demonstrated improved exercise capacity (44m improvement in 6MWD), improved WHO functional class, and increased time to clinical worsening in randomized controlled trials 3

Effective dose: 125 mg twice daily after 4-week titration from 62.5 mg twice daily 3

Dual receptor blockade (both endothelin-A and endothelin-B receptors) has proven long-term efficacy comparable to IV prostacyclin therapy 4

Drug Interactions - Critical Considerations

Bosentan interactions requiring attention: 1

• Cyclosporine: Contraindicated - bosentan levels increase 4-fold, cyclosporine levels fall 50%
• Glibenclamide: Contraindicated - increased aminotransferase elevations
• Sildenafil: Sildenafil levels fall 50%, bosentan levels increase 50% - may not require dose adjustment
• Ketoconazole: Bosentan levels increase 2-fold

Follow-Up and Monitoring

Regular assessments every 3-6 months in stable patients (Class I recommendation): 1

• WHO Functional Class
• 6-minute walk test with Borg dyspnea score
• BNP/NT-proBNP levels
• ECG
• Basic laboratory (CBC, creatinine, electrolytes, liver enzymes, bilirubin)

Every 6-12 months: 1

• Echocardiography
• Cardiopulmonary exercise testing
• Extended laboratory (TSH, troponin, uric acid, iron studies)

Right heart catheterization should be considered 3-6 months after therapy changes or with clinical worsening 1

Treatment Goals and Response Assessment

Achievement or maintenance of low-risk status is the treatment goal (Class I recommendation) 1

Intermediate-risk profile should be considered inadequate response in most patients, prompting treatment escalation (Class IIa) 1

Parameters indicating better prognosis: 1

• No clinical RV failure
• Slow symptom progression
• No syncope
• WHO-FC I-II
• 6MWD >500m
• Peak O2 consumption >15 mL/min/kg
• Normal/near-normal BNP levels
• No pericardial effusion
• TAPSE >2.0 cm, cardiac index >2.5 L/min/m², RAP <8 mmHg

Critical Warnings

Never abruptly discontinue or reduce PAH-specific therapy - all dosing changes require close monitoring 2

Referral to specialized PAH centers is strongly recommended due to diagnostic complexity and treatment options 1

Chronic thromboembolic PH (CTEPH) must be excluded with ventilation/perfusion scanning in all unexplained PH cases, as surgical pulmonary endarterectomy is curative for eligible patients 5, 6