From the Guidelines
Pulmonary arterial hypertension should be treated with a combination of medications targeting different pathways, as outlined in the most recent guideline update from 2019 1. The treatment approach for pulmonary arterial hypertension (PAH) has evolved significantly over the years, with the development and approval of 14 medications, as noted in the 2019 update of the Chest guideline and expert panel report 1.
Key Treatment Considerations
- First-line therapy often includes phosphodiesterase-5 inhibitors or endothelin receptor antagonists.
- For more severe cases, prostacyclin pathway medications may be added.
- Supportive measures, such as diuretics, oxygen therapy, and anticoagulation, are also important.
- Regular follow-up with a PAH specialist is crucial to monitor disease progression and treatment response. The 2019 guideline update provides a visual algorithm to enhance clinical utility, representing the fourth iteration of the American College of Chest Physicians Guideline and Expert Panel Report on Pharmacotherapy for PAH 1.
Medication Options
- Phosphodiesterase-5 inhibitors: sildenafil (20-80 mg three times daily) or tadalafil (40 mg once daily)
- Endothelin receptor antagonists: ambrisentan (5-10 mg daily), bosentan (62.5-125 mg twice daily), or macitentan (10 mg daily)
- Prostacyclin pathway medications: epoprostenol, treprostinil, or selexipag (oral, titrated to maximum tolerated dose up to 1600 mcg twice daily) These medications work by promoting vasodilation, inhibiting cell proliferation, and improving right ventricular function to reduce the workload on the heart, as outlined in the guideline update 1.
Additional Considerations
- Lung transplantation may be considered for patients who fail to respond to medical therapy.
- Regular assessments of functional capacity, echocardiography, and right heart catheterization are necessary to monitor disease progression and treatment response.
From the FDA Drug Label
Epoprostenol for injection is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity. Sildenafil tablets are a prescription medicine used in adults to treat pulmonary arterial hypertension (PAH). With PAH, the blood pressure in your lungs is too high. Your heart has to work hard to pump blood into your lungs. Sildenafil tablets improve the ability to exercise and can slow down worsening changes in your physical condition
Treatment Options for Pulmonary Arterial Hypertension (PAH)
- Epoprostenol (IV) is indicated for the treatment of PAH (WHO Group 1) to improve exercise capacity 2.
- Sildenafil (PO) is used in adults to treat PAH, improving the ability to exercise and slowing down worsening changes in physical condition 3.
From the Research
Definition and Classification of Pulmonary Arterial Hypertension
- Pulmonary arterial hypertension (PAH) is a subtype of pulmonary hypertension (PH), characterized by pulmonary arterial remodeling 4.
- PAH is hemodynamically defined by right heart catheterization demonstrating a mean pulmonary artery pressure greater than 20 mm Hg, a pulmonary artery wedge pressure of 15 mm Hg or lower, and a pulmonary vascular resistance of 3 Wood units or greater 4.
- PAH is classified into subgroups based on underlying etiology, consisting of idiopathic PAH, heritable PAH, drug- and toxin-associated PAH, pulmonary veno-occlusive disease, PAH in long-term responders to calcium channel blockers, and persistent PH of the newborn, as well as PAH associated with other medical conditions including connective tissue disease, HIV, and congenital heart disease 4.
Diagnosis and Treatment of Pulmonary Arterial Hypertension
- Early presenting symptoms of PAH are nonspecific and typically consist of dyspnea on exertion and fatigue 4.
- Diagnosis of PAH involves a detailed history, thorough physical examination, echocardiography, and exclusion of other causes of symptoms 5.
- Right heart catheterization is required to confirm the diagnosis of PAH 4, 5.
- Currently approved therapy for PAH consists of drugs that enhance the nitric oxide-cyclic guanosine monophosphate biological pathway, prostacyclin pathway agonists, and endothelin pathway antagonists 4.
- Combination therapy has been shown to improve pulmonary arterial pressure and morbidity and mortality compared with single-pathway targeted monotherapy 4, 6.
Efficacy of Endothelin Receptor Antagonists in Pulmonary Arterial Hypertension
- Endothelin receptor antagonists have shown efficacy in the treatment of PAH, improving exercise capacity, WHO functional class, and cardiopulmonary haemodynamics 7, 6.
- The use of endothelin receptor antagonists is associated with a reduced risk of functional class deterioration and may reduce mortality 6.
- However, endothelin receptor antagonists may increase the risk of hepatic toxicity, and monitoring of liver function is essential 6.