What are the treatment options for pulmonary hypertension (PH)?

From the Guidelines

Pulmonary hypertension treatment should prioritize medications that reduce pressure in the pulmonary arteries and improve symptoms, with a focus on phosphodiesterase-5 inhibitors, endothelin receptor antagonists, and prostacyclin analogs, as outlined in the 2019 Chest guideline update 1. The primary goal of treatment is to improve exercise capacity, quality of life, and potentially extend survival.

Key Medications

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

Treatment Approach

• Medications should be tailored to the individual patient's needs and response to treatment
• Combination therapy may be considered for patients with advanced disease or inadequate response to monotherapy 1
• Supportive measures, such as oxygen therapy, diuretics, and anticoagulation, may be necessary to manage symptoms and prevent complications
• Lung transplantation may be considered for severe cases unresponsive to medical therapy The 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension provide additional context and recommendations for managing this complex condition 1. However, the 2019 Chest guideline update 1 provides the most recent and highest-quality evidence for guiding treatment decisions.

From the FDA Drug Label

Treprostinil injection is indicated for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. The infusion rate is initiated at 1.25 ng/kg/min. If this initial dose cannot be tolerated because of systemic effects, reduce the infusion rate to 0.625 ng/kg/min. The infusion rate should be increased in increments of 1.25 ng/kg/min per week for the first four weeks of treatment and then 2.5 ng/kg/min per week for the remaining duration of infusion, depending on clinical response.

Treatment of Pulmonary Hypertension:

• Treprostinil injection can be used to treat pulmonary arterial hypertension (PAH) by diminishing symptoms associated with exercise.
• The initial dose is 1.25 ng/kg/min, which can be adjusted based on clinical response.
• Dosage adjustments should be made in increments of 1.25 ng/kg/min per week for the first four weeks, and then 2.5 ng/kg/min per week thereafter.
• The goal of chronic dosage adjustments is to establish a dose at which PAH symptoms are improved, while minimizing excessive pharmacologic effects of treprostinil injection 2.
• Tadalafil tablets are also marketed as ADCIRCA for the treatment of pulmonary arterial hypertension 3.

From the Research

Treatment Options for Pulmonary Hypertension

• Standard treatment options include oral anticoagulation, diuretics, oxygen supplementation, and for a small percentage of patients, calcium channel blockers 4.
• Newer treatments include prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors 4, 5, 6.
• Targeted treatments, such as phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin analogues, and prostacyclin receptor agonists, are licensed for patients with PAH 5.
• Surgical pulmonary endarterectomy is the treatment of choice for eligible patients with CTEPH 5.
• Management of PH resulting from left-sided heart disease primarily involves treatment of the underlying condition 5.

Combination Therapy

• Combination drug therapy that targets more than one biological pathway has shown demonstrable improvement in morbidity and mortality compared to single-pathway targeted monotherapy 7.
• First-line therapy with drug combinations that target multiple biological pathways is associated with improved survival 7.
• Examples of combination therapies include targeting the nitric oxide-cyclic guanosine monophosphate and endothelin pathways (e.g., ambrisentan and tadalafil) 7.

Approved Therapies

• Currently approved therapies for PAH include drugs that enhance the nitric oxide-cyclic guanoside monophosphate biological pathway (e.g., sildenafil, tadalafil, or riociguat), prostacyclin pathway agonists (e.g., epoprostenol or treprostinil), and endothelin pathway antagonists (e.g., bosentan and ambrisentan) 7.
• The therapeutic armamentarium for PAH now includes 13 approved therapies 8.