What are the treatment options for pulmonary hypertension?

Treatment of Pulmonary Hypertension

Diagnostic Confirmation and Risk Stratification

Right heart catheterization must be performed to confirm the diagnosis of pulmonary arterial hypertension (PAH) and guide all treatment decisions 1, 2. During this procedure, acute vasoreactivity testing should be performed in all patients with idiopathic, heritable, or drug-induced PAH to identify the approximately 10% who will respond to calcium channel blockers 2.

Risk stratification is essential before initiating therapy and should include:

• WHO functional class assessment 2, 3
• 6-minute walk distance 2, 3
• BNP or NT-proBNP levels 2
• Echocardiographic parameters 2, 3
• Hemodynamic measurements 2, 3

Patients should be classified as low, intermediate, or high risk, with reassessment every 3-6 months in stable patients 1, 2.

Treatment Algorithm for Pulmonary Arterial Hypertension (WHO Group 1)

For Vasoreactive Patients

High-dose calcium channel blockers (amlodipine, diltiazem, or nifedipine) are the first-line therapy for patients demonstrating acute vasoreactivity during right heart catheterization 2, 3. This applies only to the small subset of patients who meet vasoreactivity criteria.

For Non-Vasoreactive or Treatment-Naïve Patients

Initial oral combination therapy with ambrisentan plus tadalafil is the preferred first-line approach for treatment-naïve low or intermediate risk patients, as it significantly delays clinical failure compared to monotherapy 1, 2. This represents the current standard of care based on the most robust evidence.

Alternative initial monotherapy options include 2:

• Phosphodiesterase-5 inhibitors (sildenafil) 2, 3
• Endothelin receptor antagonists (bosentan, macitentan) 2
• Oral prostacyclin receptor agonist (selexipag) 2, 4
• Soluble guanylate cyclase stimulator (riociguat) 2

Sequential Combination Therapy

For patients with inadequate response to initial monotherapy or double combination therapy, sequential addition of a third drug class is recommended 1, 2. Options for add-on therapy include:

• Inhaled treprostinil (titrated up to 9 inhalations or 54 mcg every 6 hours) 4
• Intravenous or subcutaneous treprostinil (initiated at 1.25 ng/kg/min, increased by 1.25 ng/kg/min per week for the first 4 weeks, then 2.5 ng/kg/min per week thereafter) 5
• Intravenous epoprostenol for NYHA Functional Class III-IV patients 6

Treatment for Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Surgical pulmonary endarterectomy in deep hypothermia circulatory arrest is the treatment of choice and potentially curative for CTEPH patients 1, 2, 7. All operability assessments and decisions regarding alternative treatments must be made by a multidisciplinary team of experts 1, 2.

For inoperable CTEPH patients or those with residual pulmonary hypertension after surgery:

• Riociguat (soluble guanylate cyclase stimulator) has proven efficacy 2, 7
• Balloon pulmonary angioplasty may be considered 1, 2

Essential Supportive Care Measures

All PAH patients require comprehensive supportive care in addition to targeted therapies 2, 3:

• Diuretics: Administer for all patients with signs of right ventricular failure and fluid retention, with careful monitoring of electrolytes and renal function 2
• Oxygen therapy: Continuous long-term oxygen is recommended when arterial blood oxygen pressure is consistently <60 mmHg or to maintain saturations >90-91% 2, 3
• Anticoagulation: Consider oral anticoagulation in idiopathic PAH, heritable PAH, and anorexigen-induced PAH, though evidence is observational 2, 3
• Immunizations: Influenza and pneumococcal vaccines are recommended 3
• Pregnancy avoidance: Pregnancy must be avoided in all PAH patients due to high maternal mortality risk 1, 2, 3

Advanced Interventions

Lung transplantation should be considered after inadequate response to initial monotherapy or combination therapy, with referral occurring soon after inadequate response is confirmed on maximal combination therapy 2.

Balloon atrial septostomy may be considered as a palliative or bridging procedure in patients deteriorating despite maximal medical therapy 2.

Critical Contraindications and Pitfalls

Never combine riociguat with PDE5 inhibitors—this combination is absolutely contraindicated 2. Other essential precautions include:

• Never abruptly cease prostacyclin infusion, as this can lead to rapid clinical deterioration 5
• Do not use conventional vasodilators (ACE inhibitors, ARBs, beta-blockers) in PAH unless specifically required for comorbidities, as they lack proven benefit 2
• All PAH-approved therapies maintain pregnancy category X contraindications 2, 4
• Avoid high altitude exposure or use supplemental oxygen during air travel to maintain saturations >91% 3

Treatment for Left Heart Disease and Lung Disease-Associated PH

PAH-approved therapies are NOT recommended for patients with pulmonary hypertension due to left heart disease or lung diseases 1, 7. Treatment should focus on the underlying cardiac or pulmonary condition. PAH-specific therapies may only be considered if there is severe right-heart strain despite optimal management of the underlying disease 8.

Care Delivery Model

All PAH patients must be managed at or in consultation with specialized pulmonary hypertension centers 1, 2. These centers should provide multidisciplinary teams including cardiology and respiratory medicine physicians, clinical nurse specialists, radiologists, and psychological/social work support 1, 2.