What is the recommended treatment for pulmonary hypertension?

Treatment of Pulmonary Hypertension

The recommended treatment for pulmonary hypertension should follow a risk-stratified approach with initial combination therapy including intravenous prostacyclin analogs for high-risk patients, and oral monotherapy or combination therapy for low to intermediate risk patients. 1

Initial Assessment and Risk Stratification

• Treatment should be guided by comprehensive risk assessment to classify patients as low, intermediate, or high risk, which determines the aggressiveness of therapy 1
• Risk assessment includes clinical evidence of right ventricular failure, rate of symptom progression, functional class, exercise capacity (6-minute walk test), and hemodynamic parameters 1
• Vasoreactivity testing should be performed in all PAH patients without contraindications to identify the small subset who may respond to calcium channel blockers 1

Treatment Algorithm Based on Risk

For High-Risk Patients (WHO FC IV or unstable WHO FC III):

• Initial combination therapy including intravenous prostacyclin analogs is strongly recommended 1
• Intravenous epoprostenol should be prioritized as it has demonstrated reduced 3-month mortality in high-risk PAH patients 1, 2
• Treprostinil injection is an alternative IV prostacyclin indicated for PAH to diminish symptoms associated with exercise 3
• Inotropic support is recommended in hypotensive patients with signs of right ventricular failure 1

For Low or Intermediate-Risk Patients (WHO FC II-III):

• Initial oral combination therapy with ambrisentan plus tadalafil is recommended as it has proven superior to monotherapy in delaying clinical failure 1
• Phosphodiesterase-5 inhibitors (sildenafil, tadalafil) are effective first-line options that improve exercise capacity, hemodynamics, and clinical status 4, 5, 6, 7
• Sequential combination therapy should be initiated if clinical response to initial therapy is inadequate 1

Supportive Therapy

• Diuretic treatment is indicated for patients with signs of right ventricular failure and fluid retention 1, 8
• Continuous long-term oxygen therapy is indicated when arterial blood O₂ pressure is consistently less than 8 kPa (60 mmHg) 1
• Oral anticoagulation should be considered in patients with idiopathic PAH, heritable PAH, and PAH due to anorexigens 1
• Supervised exercise rehabilitation should be considered for physically deconditioned patients 1, 8

Treatment of Specific PAH Groups

• For PAH due to left heart disease, optimal treatment of the underlying left heart disease is recommended 1
• For PAH due to lung diseases, optimal treatment of the underlying lung disease including long-term O₂ therapy is recommended 1
• For chronic thromboembolic pulmonary hypertension (CTEPH), surgical pulmonary endarterectomy is the recommended treatment 1

Treatment Escalation and Advanced Options

• If inadequate clinical response to initial therapy, sequential double or triple combination therapy is recommended 1
• Lung transplantation should be considered after inadequate clinical response to maximal medical therapy 1
• Balloon atrial septostomy may be considered as a palliative or bridging procedure in patients deteriorating despite maximal medical therapy 1

Common Pitfalls and Caveats

• Avoid abrupt cessation of PAH-specific therapies as this can lead to clinical deterioration and death 3
• The combination of riociguat and PDE-5 inhibitors is contraindicated due to risk of hypotension 1
• Patients with right ventricular failure are often volume overloaded, and careful volume management is imperative, especially in hypotension where vasopressors and inotropes are often required rather than fluid boluses 9
• Intubation should be avoided if possible as it may worsen right ventricular function 9
• PAH-specific drug therapy is not recommended in PH due to left heart disease or lung diseases without clinical trial evidence 1