From the Guidelines
Pulmonary hypertension should be treated with a multidisciplinary approach, including medications such as phosphodiesterase-5 inhibitors, endothelin receptor antagonists, prostacyclin analogs, and soluble guanylate cyclase stimulators, as well as supportive measures like oxygen therapy, diuretics, and anticoagulation, with the goal of improving symptoms, slowing disease progression, and enhancing quality of life 1. The treatment of pulmonary hypertension depends on the specific type and severity of the disease, and typically involves a combination of medications and supportive measures.
- Medications may include:
- Phosphodiesterase-5 inhibitors (sildenafil 20 mg three times daily or tadalafil 40 mg once daily)
- Endothelin receptor antagonists (bosentan 62.5-125 mg twice daily or ambrisentan 5-10 mg once daily)
- Prostacyclin analogs (epoprostenol, treprostinil, or iloprost)
- Soluble guanylate cyclase stimulators (riociguat 1-2.5 mg three times daily)
- Supportive measures may include:
- Oxygen therapy for those with hypoxemia
- Diuretics for fluid retention
- Anticoagulation with warfarin in selected cases Advanced cases may require combination therapy or consideration for lung transplantation. The disease results from narrowing of pulmonary arteries due to various mechanisms including vasoconstriction, vascular remodeling, inflammation, and thrombosis, leading to increased resistance to blood flow, right heart strain, and eventually right heart failure if untreated. Regular follow-up with a pulmonary hypertension specialist is essential, with periodic echocardiograms, six-minute walk tests, and sometimes right heart catheterization to monitor disease progression and treatment response 1. It is worth noting that the diagnosis of pulmonary hypertension remains challenging due to its nonspecific symptoms, and a careful history evaluation is critical to evaluate for risk factors for PH, including family history, history of drugs and toxins associated with PH 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 Classification of Pulmonary Hypertension
- Pulmonary hypertension (PH) is a hemodynamic state characterized by a resting mean pulmonary artery pressure ≧ 25 mmHg 3
- PH is classified into 5 clinical subgroups: pulmonary arterial hypertension (PAH), PH due to left-sided heart disease, PH due to chronic lung disease, chronic thromboembolic PH (CTEPH), and PH with an unclear and/or multifactorial mechanisms 4
Diagnosis of Pulmonary Hypertension
- Routine tests in patients with symptoms and physical findings suggestive of PH include electrocardiography, chest radiography, and pulmonary function tests 4
- Transthoracic echocardiography is used to estimate the probability of PH 4
- Right-sided heart catheterization is essential for accurate diagnosis and classification 4
Treatment of Pulmonary Hypertension
- Targeted treatments (phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin analogues, and prostacyclin receptor agonists) are licensed for patients with PAH 4
- Surgical pulmonary endarterectomy is the treatment of choice for eligible patients with CTEPH 4
- Management of PH resulting from left-sided heart disease primarily involves treatment of the underlying condition 4
- Combination therapy is used to maximize therapeutic benefit in PAH, with three classes of drug therapy: prostaglandins, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors 5
Current Research and Future Directions
- Recent advances in understanding the pathophysiology of PAH have led to the development of promising emerging therapies targeting dysfunctional pathways beyond endothelial dysfunction, including the TGF-β and PDGF pathways 6
- Understanding precise molecular cascade involved in PH can be useful for designing preclinical animal experiments and human clinical trials to evaluate target specific novel therapeutic interventions for the treatment of PH 7