From the Guidelines
Pulmonary hypertension (PH) should be treated with a combination of medications, supportive measures, and lifestyle modifications, with the goal of improving symptoms, quality of life, and survival, as recommended by the most recent guidelines 1. The treatment approach depends on the specific type of pulmonary hypertension, with five main classifications based on underlying cause. For Group 1 PAH (pulmonary arterial hypertension), medications include:
- Endothelin receptor antagonists (ambrisentan, bosentan)
- Phosphodiesterase-5 inhibitors (sildenafil, tadalafil)
- Soluble guanylate cyclase stimulators (riociguat)
- Prostacyclin analogs (epoprostenol, treprostinil) For Groups 2-5, treatment focuses on the underlying cause. Supportive measures include:
- Oxygen therapy for hypoxemia
- Diuretics for fluid overload (furosemide 20-80mg daily)
- Anticoagulation in select cases Lifestyle modifications are important, including:
- Moderate exercise within tolerance
- Sodium restriction (<2g/day)
- Avoiding pregnancy in severe cases Regular follow-up with echocardiography and right heart catheterization is essential to monitor disease progression, as outlined in the European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines 1. Additionally, pulmonary rehabilitation programs can benefit individuals with PAH through multiple educational and comprehensive management strategies, including exercise endurance training, as suggested by the American Thoracic Society/European Respiratory Society statement 1. The choice of treatment should be individualized, taking into account the patient's specific condition, symptoms, and response to therapy, as well as the potential risks and benefits of each treatment option, as discussed in the guidelines 1.
From the FDA Drug Label
Epoprostenol for injection is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity. Studies establishing effectiveness included predominantly patients with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH or PAH associated with connective tissue diseases.
Epoprostenol (IV) is indicated for the treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity, specifically for patients with:
- NYHA Functional Class III-IV symptoms
- Idiopathic or heritable PAH
- PAH associated with connective tissue diseases 2, 2
From the Research
Pulmonary Hypertension Overview
- Pulmonary hypertension (PH) is a condition characterized by high blood pressure in the arteries of the lungs, which can lead to right heart failure and death 3, 4, 5, 6, 7.
- Endothelin-1 (ET-1) is a key mediator in the pathophysiology of pulmonary arterial hypertension (PAH) and its effects are mediated through the activation of two associated receptor subtypes, termed A and B 5.
Treatment Options
- Endothelin receptor antagonists (ERAs) have emerged as an important therapeutic approach in PAH, improving exercise capacity, functional status, pulmonary hemodynamics, and delaying the time to clinical worsening 3, 4, 6.
- Bosentan, a dual ERA, is currently approved for patients with class III and IV PAH, while ambrisentan, a selective ERA, is approved for patients with class II and III PAH 6.
- Other treatment options for PAH include prostacyclin analogues, phosphodiesterase-5 inhibitors, and calcium channel blockers (CCBs) 7.
Efficacy and Safety of ERAs
- ERAs have been shown to improve pulmonary hemodynamics, exercise capacity, and functional status in patients with PAH 3, 4, 6.
- The most common adverse effect of ERAs is an increase in transaminases, which is reversible on dosage reduction or discontinuing the medication 4.
- Regular monitoring of liver function is recommended for patients taking ERAs 4.
Future Directions
- Comparative studies are warranted to establish whether selective endothelin-A receptor antagonism is more advantageous than dual receptor antagonism 5.
- Future studies of ERAs will increasingly focus on the potential of a combination of different PAH therapeutic classes and will employ 'harder' clinical end points 5.