Patients with PAH may experience only mild symptoms at first. However, due to the progressive nature of PAH, patients will continue to get worse and will eventually require treatment.1-3
Prostacyclin, endothelin, and nitric oxide are the 3 main pathways in PAH. Abnormalities in these pathways result in proliferation and contraction of the smooth muscle cells of the pulmonary arteries in patients with PAH. These 3 pathways correspond to important therapeutic targets in the treatment of PAH.1,2
The effects of endothelin
In PAH, levels of endothelin are significantly increased in the bloodstream and in the lungs.3,6 Excess levels of endothelin have been linked to:
Please note, OPSUMIT is not associated with the prostacyclin pathway.2,4
Prostacyclin is a potent vasodilator that has antiproliferative properties and inhibits platelet activation.9 Reduced levels of prostacyclin synthase are found in patients with IPAH.3,10
Prostacyclin levels are lower in PAH and this has been implicated in9:
Prostacyclin may play a role in:
Please note, OPSUMIT is not associated with the nitric oxide pathway.2,4
Patients with PAH have evidence of decreased nitric oxide synthase, which generates nitric oxide.3
The role of nitric oxide in PAH:
OPSUMIT is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression. Disease progression included: death, initiation of intravenous (IV) or subcutaneous prostanoids, or clinical worsening of PAH (decreased 6-minute walk distance, worsened PAH symptoms and need for additional PAH treatment). OPSUMIT also reduced hospitalization for PAH.
Effectiveness was established in a long-term study in PAH patients with predominantly WHO Functional Class II-III symptoms treated for an average of 2 years. Patients were treated with OPSUMIT monotherapy or in combination with phosphodiesterase-5 inhibitors or inhaled prostanoids. Patients had idiopathic and heritable PAH (57%), PAH caused by connective tissue disorders (31%), and PAH caused by congenital heart disease with repaired shunts (8%).
Pregnancy: OPSUMIT may cause fetal harm when administered to a pregnant woman. OPSUMIT is contraindicated in females who are pregnant. If OPSUMIT is used during pregnancy, apprise the patient of the potential hazard to a fetus.