Treprostinil-based therapy in the treatment of moderate-to-severe pulmonary arterial hypertension - Long-term efficacy and combination with bosentan

Background: Treprostinil, a long-acting prostacyclin analog, diminished the symptoms of pulmonary arterial hypertension (PAH) in controlled 12-week clinical efficacy studies. This retrospective, single-center, open-label study was designed to assess the efficacy of long-term, subcutaneously administered, treprostinil-based therapy alone or in combination with bosentan for the treatment of moderate-to-severe PAH. Methods: Thirty-eight patients with pulmonary hypertension treated with subcutaneous treprostinil were followed up for a mean (+/- SD) duration of 984 +/- 468 days (range, 165 to 1,847 days). Oral bosentan was added to the treprostinil regimen if patients remained in New York Heart Association (NYHA) functional class III or II with intolerable prostacyclin side effects that limited therapy. Hemodynamic studies, Borg dyspnea score evaluations, 6-min walk (6MW) tests, and NYHA functional class determinations were performed at approximately 6-month intervals. Results: Mean pulmonary artery pressure decreased from 59.7 to 50.5 mm Hg (p < 0.001). Significant and sustained improvement in 6MW distance (p = 0.022) and Borg dyspnea score (p = 0.023) were observed. At the final observation, the mean dose of treprostinil was 37.8 ng/kg/min (range, 7.5 to 115 ng/kg/min). At baseline, 5% of patients were in NYHA functional class 2 or lower vs 58% at the last follow-up. Bosentan was added to the regimens of 19 patients. In those patients, significant additional improvement occurred in the pulmonary arterial pressure (p < 0.001), 6MW distance (p = 0.001), and Borg dyspnea scale (p = 0.020) compared to baseline. Conclusions: Long-term treatment with subcutaneous treprostinil-based therapy improved functional parameters and hemodynamics in patients with moderate-to-severe PAH. In patients requiring combination therapy, the addition of oral bosentan to treprostinil-based therapy was safe, well-tolerated, and associated with further clinical improvements.