Long-term bosentan in chronic thromboembolic pulmonary hypertension

Background: There is no approved pharmacological treatment for patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not suitable for pulmonary endarterectomy (PEA).

Objective: The study investigates the effect of the dual endothelin receptor antagonist bosentan on exercise tolerance (6-min walking distance, 6MWD) and right ventricular function (Tei index) in patients with CTEPH over 24 months.

Methods: Twelve consecutive patients (5 males and 7 females) with CTEPH not eligible for PEA or following partial or complete failure of PEA were included in a non-randomized, open-label prospective study. All patients were WHO class III. They were included, if progressive pulmonary hypertension was diagnosed despite best supportive treatment. Bosentan was started at 62.5 mg b.i.d. and increased to the final dose of 125 mg b.i.d.

Results: 6MWD and the Tei index were assessed every 6 months. We observed a significant increase in 6MWD from 319 +/- 85.0 m at baseline to 391 +/- 76.9 m at 6 months and a significant decrease in the Tei index from 0.39 +/- 0.10 at baseline to 0.34 +/- 0.08 at 6 months. This improvement was maintained over 24 months (6 MWD: 381 +/- 101 m; Tei index: 0.31 +/- 0.03). Six patients exhibited an improvement in WHO class at 6, 12 and 18 months, 5 demonstrated improvement at the 24-month follow-up. The remainder were stable throughout the study period.

Conclusion: This is the first study demonstrating a long-term beneficial effect of bosentan on exercise tolerance (6MWD) and right heart function (Tei index) in CTEPH.