Skoro-Sajer et al in NYHA class III, and only 2 m in the 53 patients who were in NYHA class II. In fact, there was a dose relationship such that the higher the treprostinil dose achieved, the greater the increase in 6-min walk distance. Based on this observation, the aver- age dose achieved in the treprostinil group was only 9.3 ng/kg/min, far below the target 22.5 ng/kg/min dosing, thereby preventing full disclosure of treprostinil efﬁcacy. It was indeed only later the experience of many centers that infusion site pain is not directly dependent on the rate of treprostinil dose increase. Infusion site pain occurred in 85% of the treprostinil- treated patients and in 27% in the placebo-treated patients. Eighteen patients (8%) in the treprostinil group discontinued their study treatment due to intolerable abdominal infusion site pain versus one in the placebo group. Other adverse events were those classically related to the use of prostacyclin such as diarrhea, jaw pain, ﬂushing, and lower limb edema, which mainly occurred more often in the treprostinil group. There were no other signiﬁcant side effects. Long-term observations The effects of long-term subcutaneous treprostinil have been reported in 860 patients with PAH (Barst et al 2006). In that study, the initial clinical improvement was sustained in the majority of patients, and survival was globally 87% at 1 year and 68% at 4 years, with 91%–72% for a subset of IPAH patients. In 23% of the patients, the treatment was discontinued because of adverse events, and in 11% switched to an alternative prostacyclin analogue. Bosentan was added in 105 patients (12%) and sildenaﬁl in 25 (3%). In another long-term observational study on a total of 99 PAH patients and 23 inoperable CTEPH patients, the NYHA functional class declined from 3.2 to 2.1 with persistent improvement in the 6-min walk distance, on average by 100 m (Figure 2). The 1- and 3-year survival rates were 89% and 71%, with, interestingly, event-free survival rates of 83% and 69%. The mean dose of treprostinil at 3 years was on average around 40 ng/kg/min (Figure 3). There were only 5% of treatment interruptions because of local infusion site pain. These long-term observations suggest that subcutaneous treprostinil is a valid alternative to intravenous epoprostenol as a gold standard of PAH therapy (Galie et al 2004; Badesch et al 2007). Transitioning Transition from intravenous epoprostenol to subcutaneous treprostinil has been achieved in a number of patients. Ini- tially undertaken because of life-threatening complications of chronic intravenous epoprostenol therapy, such as embolic stroke and repeated sepsis (Vachiery et al 2002), the proce- dure is now also performed in several centers on the request of patients for the purpose of increased autonomy and comfort. Transitioning should be performed in a hospital environment Figure 2 Long-term effects of subcutaneous treprostinil on exercise capacity in patients with severe pulmonary hypertension, with indication of treprostinil dose and 6MWD (6-min walk distance). Drawn from data of Lang et al (2006). 510 Vascular Health and Risk Management 2008:4(3)