What is the treatment for pulmonary hypertension?

Treatment of Pulmonary Hypertension

For treatment-naïve pulmonary arterial hypertension (PAH) patients at low or intermediate risk, initial oral combination therapy with ambrisentan plus tadalafil is superior to monotherapy and should be the preferred approach. 1

Critical First Step: Confirm Diagnosis and Classification

Before initiating any PAH-specific therapy, the following must be completed:

• Right heart catheterization is mandatory to confirm the diagnosis (mean pulmonary artery pressure ≥25 mmHg, pulmonary capillary wedge pressure ≤15 mmHg) and establish hemodynamic classification 1
• Vasoreactivity testing must be performed in patients with idiopathic, heritable, or drug-induced PAH to identify the ~10% who may respond to calcium channel blockers 1
• All patients should be evaluated at an expert pulmonary hypertension center before starting treatment, as therapeutic approach differs fundamentally based on PH classification 1

Treatment Algorithm for Pulmonary Arterial Hypertension (Group 1)

For Vasoreactive Patients (Positive Acute Vasoreactivity Test)

• High-dose calcium channel blockers are first-line therapy for the small subset demonstrating acute vasoreactivity during right heart catheterization 1

For Non-Vasoreactive Patients: Risk-Stratified Approach

Risk stratification should incorporate WHO functional class, 6-minute walk distance, BNP/NT-proBNP levels, and echocardiographic/hemodynamic parameters 1

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
• Alternative: Initial monotherapy with approved PAH drugs (sildenafil 2, endothelin receptor antagonists, or prostacyclin analogs) may be considered 1

High Risk Patients (WHO FC IV):

• Initial combination therapy including intravenous prostacyclin analogs should be prioritized 1
• Intravenous epoprostenol should be the preferred prostacyclin as it is the only therapy proven to reduce 3-month mortality in high-risk PAH patients 1, 3

Sequential Combination Therapy

• If inadequate clinical response occurs (failure to achieve/maintain low-risk status), escalate to double or triple sequential combination therapy 1
• Never combine riociguat with PDE-5 inhibitors - this combination is contraindicated 1

Treatment for Other Pulmonary Hypertension Groups

Group 2 (Left Heart Disease):

• PAH-specific therapies are NOT recommended and may be harmful 1
• Treatment should focus on optimizing the underlying cardiac condition 4

Group 3 (Lung Disease):

• Long-term oxygen therapy is recommended to maintain saturations >90% and has been shown to partially reduce PH progression in COPD 4
• PAH-specific vasodilators are NOT recommended as they may worsen gas exchange 1, 4
• Conventional vasodilators (calcium channel blockers) should be avoided as they can worsen ventilation-perfusion matching 4

Group 4 (Chronic Thromboembolic PH):

• Surgical pulmonary endarterectomy in deep hypothermia with circulatory arrest is the treatment of choice 1
• Operability assessment and treatment decisions must be made by a multidisciplinary expert team 1

Essential Supportive Care Measures

Diuretics:

• Recommended for all PAH patients with signs of right ventricular failure and fluid retention 1
• Monitor electrolytes and renal function carefully during active diuresis 4

Oxygen Therapy:

• Continuous long-term oxygen is recommended when arterial oxygen pressure is consistently <60 mmHg or to maintain saturations >90% 1, 4

Anticoagulation:

• Should be considered in idiopathic PAH, heritable PAH, and anorexigen-induced PAH, targeting INR 1.5-2.5 (2-3 for chronic thromboembolic PH) 4

Pregnancy:

• Must be avoided in all PAH patients due to high mortality risk 1, 4

Monitoring and Treatment Goals

• Regular assessments every 3-6 months should include WHO functional class, 6-minute walk distance, BNP/NT-proBNP, and echocardiography 1
• The primary goal is achieving and maintaining low-risk status (typically WHO FC I-II) 1
• Target 6-minute walk distance >440 meters for most patients, though lower values may be acceptable in elderly patients or those with significant comorbidities 1

Advanced Therapies and Rescue Options

• Consider eligibility for lung transplantation after inadequate response to initial monotherapy or combination therapy 1
• Refer for transplantation soon after inadequate response is confirmed on maximal combination therapy 1
• Balloon atrial septostomy may be considered as a palliative or bridging procedure in patients deteriorating despite maximal medical therapy 1

Critical Pitfalls to Avoid

• Do not start PAH-specific drugs empirically without confirming diagnosis and classification via right heart catheterization, as this can delay appropriate treatment and cause harm, particularly in Group 2 PH 4
• Avoid ACE inhibitors, ARBs, and beta-blockers in PAH unless specifically required for comorbidities, as they lack proven benefit 1
• Do not attempt complete workup locally without specialist input, as this often results in incomplete phenotyping and inappropriate therapy 1

Urgent/Critical Care Situations

• ICU hospitalization is recommended for PH patients with high heart rate (>110 bpm), low blood pressure (systolic <90 mmHg), low urine output, or rising lactate 1
• Inotropic support is recommended for hypotensive patients 1
• Intubation should be avoided if possible, as positive pressure ventilation can worsen right ventricular function 5