under the supervision of a medical team experienced in the treatment of PAH. Under noninvasive hemodynamic moni- toring including heart rate and blood pressure measurements and echocardiography as needed, epoprostenol is progres- sively decreased and treprostinil increased, with overdosing and underdosing symptoms-directed adjustments, in no more than 1–4 days. Usually the same clinical state and exercise capacity is obtained under a treprostinil dose that is about 80% of the previous epoprostenol dose. Most transitioned patients express satisfaction and relief, in spite of local infusion site pain, and present with continued improvement in exercise capacity over time. There has been recently a report on 22 PAH patients treated with intravenous epoprostenol who were randomized for 8 weeks to subcutaneous treprostinil versus a placebo (Rubenﬁre et al 2007). This represents the only withdrawal trial reported in PAH. Even though the protocol speciﬁed that patients with clinical deterioration would be rapidly returned to intravenous epoprostenol, most experts would be reluctant to repeat such a study. Patients who deteriorate after inter- ruption of any prostacyclin therapy may be difﬁcult to bring back to their previous clinical state. However, no irreversible deterioration occurred in this tightly monitored trial. Seven of the 8 patients withdrawn to placebo had the expected clinical deterioration, while this was observed in only 1 of the 14 patients withdrawn to subcutaneous treprostinil. The authors concluded that subcutaneous treprostinil is Treprostinil for pulmonary hypertension effective in PAH and maintains functional status in patients transitioned from intravenous epoprostenol (Rubenﬁre et al 2007). Treprostinil can be formulated for intravenous adminis- tration. Intravenous treprostinil has been reported to improve exercise capacity, Borg dyspnea score, NYHA functional class, and hemodynamics after 12 weeks of therapy compared with baseline (Tapson et al 2006). Accordingly, patients treated with intravenous epoprostenol have been safely switched to intravenous treprostinil (Gomberg-Maitland et al 2005; Sitbon et al 2007). However, while the dosing of sub- cutaneous treprostinil is about the same as that of intravenous epoprostenol (Vachiery et al 2002), the dose of intravenous treprostinil has been reported to be at least doubled to main- tain the clinical beneﬁt (Gomberg-Maitland et al 2005; Sitbon et al 2007). Patients have also been switched from subcutane- ous to intravenous treprostinil in several PAH centers, with the same apparent need to rapidly double the dose to attain similar efﬁcacy. There is no explanation for this discrepancy, as bioequivalence of intravenous and subcutaneous trepro- stinil has been reported in normal volunteers at steady state, after 72 hours of continuous administration (Labilerte et al 2004). Most recently, this bioequivalence, with the same dose versus plasma levels relationship, was conﬁrmed for PAH patients over a wide range of therapeutic doses, up to 125 ng kg/min (McSwain et al 2008). The problem of optimal dosing with intravenous versus subcutaneous treprostinil in Figure 3 Effects of subcutaneous treprostinil on survival in patients with idiopathic pulmonary arterial hypertension (PAH). Survival curves of similar patients treated with intravenous epoprostenol and those of historical controls are also shown. Drawn from data of McLaughlin et al (2002) and Lang et al (2006). Vascular Health and Risk Management 2008:4(3) 511