From the Guidelines
Pulmonary hypertension treatment should prioritize a systematic and consistent evaluation of disease severity, using a combination of World Health Organization (WHO) functional class, exercise capacity, echocardiographic, laboratory, and hemodynamic variables to inform therapeutic decisions, as recommended by the most recent guideline update 1. The treatment of pulmonary hypertension depends on the specific type, with pulmonary arterial hypertension (Group 1) being the most common. Medications for Group 1 include:
- Phosphodiesterase-5 inhibitors (sildenafil 20mg three times daily or tadalafil 40mg once daily)
- Endothelin receptor antagonists (bosentan 62.5mg twice daily for 4 weeks, then 125mg twice daily)
- Prostacyclin analogs (epoprostenol, treprostinil)
- Soluble guanylate cyclase stimulators (riociguat) Supportive care includes:
- Oxygen therapy for hypoxemia
- Diuretics for fluid retention
- Anticoagulation in selected cases Advanced cases may require combination therapy or consideration for lung transplantation. Regular monitoring with echocardiography, 6-minute walk tests, and right heart catheterization is essential to assess disease progression and treatment response, as emphasized in the guideline update 1. Key considerations in managing pulmonary hypertension include:
- Collaborative and closely coordinated care involving local physicians and those with expertise in PAH care, as suggested by the guideline 1
- Evaluation of patients at a center with expertise in PAH diagnosis, ideally prior to initiating therapy, as recommended by the guideline 1
- Lifestyle modifications, such as moderate exercise within tolerance, avoiding pregnancy, maintaining vaccinations, and avoiding high altitudes. The disease progresses due to vascular remodeling, vasoconstriction, and thrombosis, leading to increased right ventricular workload and eventual right heart failure, highlighting the importance of prompt and appropriate treatment, as noted in the guideline update 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
From the Research
Definition and Causes of Pulmonary Hypertension
- Pulmonary hypertension is a group of diseases characterized by a progressive increase of pulmonary vascular resistance (PVR), initially due to abnormal pulmonary vasoconstriction in response to endothelial injury 3.
- Endothelin 1, a powerful endogenous vasoconstrictor and mitogen, might be a cause of pulmonary hypertension 4.
Treatment Options for Pulmonary Hypertension
- Endothelin receptor antagonists (ERAs) are indicated in non-vasoreactive patients or in vasoreactive patients not responding to initial calcium channel blocker therapy 3.
- Bosentan, a dual endothelin-receptor antagonist, is an effective and well-tolerated oral therapy for the management of pulmonary arterial hypertension (PAH; WHO group 1 pulmonary hypertension) 5.
- ERAs improve pulmonary haemodynamics, exercise capacity, functional status and clinical outcome in patients with PAH 3, 6.
Benefits and Efficacy of Endothelin Receptor Antagonists
- Bosentan increases exercise capacity and improves haemodynamics in patients with pulmonary hypertension, suggesting that endothelin has an important role in pulmonary hypertension 4.
- Endothelin receptor antagonists have been shown to improve cardiopulmonary hemodynamics, exercise capacity, WHO functional class and quality of life, as well as delaying time to clinical worsening in patients with PAH 5, 6.
- Preliminary evidence suggests that bosentan and ambrisentan may be beneficial in pulmonary hypertension in patients with sickle cell disease 7.
Adverse Events and Future Research
- Adverse events associated with endothelin receptor antagonists include increased serum alanine aminotransferase, peripheral oedema, rash, headache, and decreased haemoglobin 7.
- Future studies of endothelin receptor antagonists will increasingly focus on the potential of a combination of different PAH therapeutic classes and will employ 'harder' clinical end points 6.