Treprostinil for severe inoperable chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) results from non-resolving pulmonary thromboemboli that are resistant to plasmatic anticoagulation. Because of a secondary pulmonary arteriopathy accompanying major vessel obstruction, the disorder may be a target for vasodilator therapy.

In an open-label uncontrolled study, we investigated the prostacyclin analog treprostinil given s.c. in patients with severe inoperable CTEPH.

Between September 1999 and September 2005, 25 patients were included if their World Health Organization (WHO) functional class was III or IV, if their six-minute walking distance (6-MWD)

Treprostinil-treated patients demonstrated significant improvements in 6-MWD (P = 0.01), WHO functional class (P = 0.001), B-type brain natriuretic peptide plasma levels (P = 0.02), cardiac outputs (P = 0.007) and pulmonary vascular resistances (P = 0.01) after 19 +/- 6.3 months. Treprostinil plasma concentrations correlated with drug dose (P < 0.001), indicating stable absorption over time. Long-term survival was significantly better than in controls.

Treprostinil improves exercise capacity, hemodynamics and survival in patients with severe inoperable CTEPH. We speculate that the effects may be explained by a combined vasodilatory, platelet-antagonistic and potential antiproliferative action of the drug.