Safety and efficacy of inhaled treprostinil as add-on therapy to bosentan in pulmonary arterial hypertension

OBJECTIVES This study evaluated the safety and efficacy of inhaled treprostinil as add-on therapy to oral bosentan in patients with pulmonary arterial hypertension (PAH). BACKGROUND The addition of a long-acting prostacyclin analogue via the inhaled route might be a safe and effective strategy to optimize therapy in PAH patients on bosentan. METHODS Twelve patients with symptomatic PAH despite bosentan received either 30 mu g of inhaled treprostinil 4 times daily (n = 6) or 45 mu g 4 times daily (n = 6), via an ultrasonic nebulizer. Six-min walk distance (6MWD), functional class, and hemodynamics were assessed at baseline and 12 weeks. RESULTS One patient was excluded from analysis due to the subsequent finding of pulmonary capillary hemangiomatosis. In the remaining 11 patients, inhaled treprostinil was safe and well tolerated. Inhaled treprostinil was associated with an increase in 6MVVD at 12 weeks (baseline 339 +/- 86, 12 week, 1 h post-inhalation 406 +/- 121 in, 67-m change, p = 0.01). An improvement in 6MVVD of 49 in from baseline was noted during the trough period, just before inhalation of treprostinil (p = 0.009). The 6MVVD improvement of at least 10% was noted in 1 of 6 patients receiving 30 mu g versus 5 of 6 receiving 45 mu g. Over 12 weeks, significant decreases were noted in mean pulmonary arterial pressure (-10%) and in pulmonary vascular resistance (-26%). Functional class improved from III to II in 9 of 11 patients. CONCLUSIONS This trial suggests that inhaled treprostinil is safe, well tolerated, and associated with significant improvements in exercise capacity, functional class, and pulmonary hemodynamics in symptomatic patients with PAH on bosentan.