From the Guidelines
For pulmonary arterial hypertension (PAH), the most recent and highest quality evidence recommends initial combination therapy with ambrisentan and tadalafil to improve 6MWD, as suggested by the 2019 Chest guideline and expert panel report 1. This approach is based on the understanding that PAH is a complex disease requiring multifaceted treatment strategies. The medications used can be categorized into several classes, including:
- Phosphodiesterase-5 inhibitors like sildenafil (20mg three times daily) or tadalafil (40mg once daily), which promote vasodilation by increasing nitric oxide availability.
- Endothelin receptor antagonists such as ambrisentan (5-10mg daily), bosentan (62.5-125mg twice daily), or macitentan (10mg daily), which block the vasoconstricting effects of endothelin.
- Prostacyclin pathway agents, including oral selexipag (200-1600mcg twice daily), inhaled treprostinil (3-9 breaths four times daily), or intravenous epoprostenol (initiated at 2ng/kg/min and titrated upward), which improve symptoms by promoting vasodilation and inhibiting platelet aggregation. The choice of specific medications depends on PAH severity, functional class, patient comorbidities, and medication side effect profiles, with the goal of improving exercise capacity, quality of life, and survival, as outlined in the 2019 update of the Chest guideline and expert panel report 1.
Key considerations in the management of PAH include:
- Prompt initiation of treatment after diagnosis
- Regular monitoring of clinical response, side effects, and disease progression
- Adjustment of therapy based on patient response and tolerance
- Consideration of combination therapy for advanced PAH, as supported by the most recent evidence 1
- Patient education on the importance of adherence to prescribed therapy and follow-up appointments
In patients with WHO FC III symptoms, initial combination therapy with ambrisentan and tadalafil is advised, as stated in Recommendation #10 of the 2019 Chest guideline and expert panel report 1. For those who are unwilling or unable to tolerate combination therapy, monotherapy with a currently approved ERA, a PDE5I, or the soluble guanylate cyclase stimulator riociguat may be considered, as outlined in the 2019 update of the Chest guideline and expert panel report 1.
From the FDA Drug Label
Ambrisentan tablets are indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): To improve exercise ability and delay clinical worsening 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
The medications recommended for Pulmonary Arterial Hypertension (PAH) are:
From the Research
Medications for Pulmonary Arterial Hypertension (PAH)
The following medications are recommended for the treatment of PAH:
- Phosphodiesterase type-5 inhibitors (sildenafil, tadalafil) 4, 5
- Soluble guanylate cyclase stimulators (riociguat) 4, 5
- Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) 4, 5, 6
- Prostacyclin analogs (epoprostenol, treprostinil) 4, 5, 7, 8
- Prostacyclin receptor agonists 5
Combination Therapy
Combination therapy targeting multiple biological pathways is recommended for patients with PAH, including:
- Phosphodiesterase type-5 inhibitor and endothelin receptor antagonist for low- and intermediate-risk patients 5
- Triple therapy including a parenteral prostacyclin for high- or intermediate-high risk patients 5
Treatment Considerations
Treatment considerations include: