Treprostinil for severe inoperable chronic thromboembolic pulmonary hypertension

Background: 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. Objectives: In an open-label uncontrolled study, we investigated the prostacyclin analog treprostinil given s.c. in patients with severe inoperable CTEPH. Methods: 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) <= 380 m, and if they had undergone at least one hospitalization for right heart decompensation within the prior six months, albeit not within one month before treatment start. Right heart catheterization was performed at baseline and after a minimum of 12 months (range: 12-33 months) of treatment. Treprostinil plasma concentrations were determined after at least six months of treatment. A historical group of 31 patients at our center with inoperable CTEPH matched for disease severity was used for comparative analyses. Results: 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. Conclusions: Treprostinil improves exercise capacity, hemodynamics and survival in patients with severe inoperable CTEPH. We speculate that the effects may be explained by a combined vasodilatatory, platelet-antagonistic and potential antiproliferative action of the drug.