What are the treatment options for Pulmonary Arterial Hypertension (PAH) medication?

From the Guidelines

Pulmonary arterial hypertension (PAH) treatment should typically involve a combination of medications, with initial therapy often including an endothelin receptor antagonist (ERA) such as ambrisentan (5-10mg daily) or macitentan (10mg daily) combined with a phosphodiesterase-5 inhibitor (PDE5i) like sildenafil (20mg three times daily) or tadalafil (40mg once daily), as recommended by the 2019 Chest guideline update 1.

Medication Options

The following medications are currently approved for the treatment of PAH:

• Prostacyclin derivatives: epoprostenol (IV infusion, 2 ng/kg/min), iloprost (inhaled, 2.5 or 5.0 mg 6-9 inhalations/d), treprostinil (oral, 0.25 mg bid or 0.125 mg tid; inhaled, 18–54 mg 4 times daily; subcutaneous or IV infusion, 1.25 ng/kg/min)
• Endothelin receptor antagonists: bosentan (oral, 125 mg twice daily), ambrisentan (oral, 5 or 10 mg once daily), macitentan (oral, 10 mg once daily)
• Phosphodiesterase type-5 inhibitors: sildenafil (oral, 20 mg every 8 h), tadalafil (oral, 40 mg once daily)
• Soluble cGMP stimulators: riociguat (oral, 0.5-1.0 mg every 8 h)
• Prostacyclin receptor agonists: selexipag (oral, 200 mg twice daily, increase as tolerated to maximum dose of 1,600 mg twice daily)

Treatment Approach

Treatment should be individualized based on disease severity, comorbidities, and patient preferences. Combination therapy is now standard of care as it targets multiple disease pathways simultaneously. Regular monitoring of liver function, hemoglobin, and clinical response is essential, with treatment adjustments made based on clinical worsening or improvement. Supportive care including diuretics for fluid management, oxygen therapy when indicated, and anticoagulation in specific cases completes the treatment approach. The 6-minute walk distance (6MWD) is a commonly used outcome measure, with a minimally important difference (MID) of 33 m defining clinically significant improvement 1.

Key Considerations

• The choice of medication and treatment approach should be guided by the patient's specific needs and circumstances.
• Regular follow-up and monitoring are crucial to ensure optimal treatment outcomes.
• The treatment approach should be tailored to the individual patient, taking into account their disease severity, comorbidities, and preferences.

From the FDA Drug Label

Selexipag tablets are indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH. Sildenafil tablets are a prescription medicine used in adults to treat pulmonary arterial hypertension (PAH). The treatment for PAH includes medications such as selexipag and sildenafil.

• Selexipag is indicated to delay disease progression and reduce the risk of hospitalization for PAH.
• Sildenafil is used to treat PAH and improve the ability to exercise and can slow down worsening changes in physical condition 2 3.

From the Research

PAH Medication Treatment

• PAH medication treatment includes drugs that enhance the nitric oxide-cyclic guanosine monophosphate biological pathway, prostacyclin pathway agonists, and endothelin pathway antagonists 4.
• Current treatment consists of combination drug therapy that targets more than one biological pathway, such as the nitric oxide-cyclic guanosine monophosphate and endothelin pathways, and has shown demonstrable improvement in morbidity and mortality compared with single-pathway targeted monotherapy 4.
• Endothelin receptor antagonists, such as bosentan, have been shown to increase exercise capacity and improve hemodynamics in patients with pulmonary hypertension 5, 6.
• Bosentan is an orally active, nonpeptide endothelin receptor antagonist that produces pulmonary vasodilation, improving cardiopulmonary hemodynamics and leading to better outcomes for patients 6.
• The use of bosentan in patients with WHO functional class III and IV PAH is associated with improved exercise tolerance, cardiopulmonary hemodynamics, and increased time to clinical worsening when compared with placebo 6.
• Endothelin receptor antagonists, including bosentan, sitaxsentan, and ambrisentan, have become mainstays in the current treatment of PAH, and have been shown to improve exercise capacity, WHO functional class, and cardiopulmonary hemodynamics 7, 8.
• A systematic review of 17 randomized controlled trials found that endothelin receptor antagonists probably increase exercise capacity, improve WHO functional class, and prevent WHO functional class deterioration in patients with PAH 8.
• However, the review also found that endothelin receptor antagonists may be less effective in reducing dyspnea and mortality, and that hepatic toxicity is a potential side effect of these medications 8.