Efficacy of long-term subcutaneous treprostinil sodium therapy in pulmonary hypertension.

STUDY OBJECTIVES: The aim of this long-term multicenter analysis was to investigate whether subcutaneously infused treprostinil could provide sustained improvements of exercise capacity and survival benefits in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Subcutaneous administration of the prostacyclin analog treprostinil is an effective treatment for PAH that, unlike epoprostenol, does not require the insertion of a permanent central venous catheter.

DESIGN: Multicenter retrospective study.

SETTING: Three European university hospitals.

METHODS: Ninety-nine patients with PAH and 23 patients with CTEPH in New York Heart Association (NYHA) classes II-IV were followed up for a mean of 26.2 +/- 17.2 months (+/- SE) [range, 3 to 57 months]. Long-term efficacy was assessed by 6-min walking distance (SMWD), Borg dyspnea score, and NYHA class. Clinical events were monitored to assess survival and event-free survival.

RESULTS: At 3 years, significant improvements from baseline were observed in mean SMWD (305 +/- 11 to 445 +/- 12 m, p = 0.0001), Borg dyspnea score (5.7 +/- 0.2 to 4.5 +/- 1, p = 0.0006), and NYHA class (3.20 +/- 0.04 to 2.1 +/- 0.1, p = 0.0001). These changes were observed under a mean dose of subcutaneously infused treprostinil at 40 +/- 2.6 ng/kg/min (range, 16 to 84 ng/kg/min). Subcutaneously infused treprostinil was well tolerated, and local pain at the subcutaneous site accounted for treatment interruption in only 5% of the cases. Survival was 88.6% and 70.6% at 1 year and 3 years, respectively. At the same time points, the event-free survival rates, defined as survival without hospitalization for clinical worsening, transition to IV epoprostenol, and need for combination therapy or atrial septostomy, were 83.2% and 69%, respectively.

CONCLUSIONS: Long-term subcutaneous therapy with treprostinil appears to continuously improve exercise tolerance and symptoms in patients with PAH and inoperable CTEPH. Moreover, treatment may provide a significant survival benefit.