The Role of Treprostinil in the Management of Pulmonary Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a severely disabling disorder characterized by sustained elevations of pulmonary vascular resistance, ultimately leading to right-heart failure and death. Intravenous epoprostenol has been widely used in patients with PAH, leading to long-term clinical benefits and improved survival. Epoprostenol has to be delivered through a permanently implanted intravenous catheter, with the potential of life-threatening complications. Thus, treprostinil, a stable prostacyclin analog suitable for subcutaneous administration, has been developed. Treprostinil is chemically stable at room temperature, has a long half-life (2-4 hours), and has similar pharmacologic properties with comparable hemodynamic effects as epoprostenol.A large, double-blind, placebo-controlled, multicenter, 12-week study confirmed the efficacy of subcutaneous treprostinil, by improving exercise capacity, Borg Dypnea Score (BDS), New York Heart Association (NYHA) class, and clinical signs and symptoms in patients with PAH. Subsequently, multiple observational studies reported the long-term effects of subcutaneous treprostinil. The long-term survival of patients treated with subcutaneous treprostinil was similar to that reported with intravenous epoprostenol. Pain at the infusion site has been a major drawback of subcutaneous treprostinil, hampering dose titration and leading to an 8-10% discontinuation rate. In addition, studies have examined the efficacy of intravenous treprostinil in the treatment of patients with PAH. An open-label study demonstrated that intravenous treprostinil improved exercise capacity, BDS, NYHA functional class, and hemodynamics at week 12 compared with baseline. Transitioning from intravenous epoprostenol to intravenous treprostinil is safe and effective. The dose of intravenous treprostinil has to be adjusted to approximately twice the dose of intravenous epoprostenol. Most patients have reported less severe adverse effects with intravenous treprostinil compared with intravenous epoprostenol. The assessment of the long-term efficacy and safety of continuous intravenous treprostinil requires further studies.

Subcutaneous implantation of a new intravenous pump system for prostacyclin treatment in patients with pulmonary arterial hypertension

“…14 Unfortunately, pain at the infusion site is a major drawback of subcutaneous treatment, hampering dose titration and leading to a 5% to 10% discontinuation rate. 14,15 Meanwhile, the intravenous delivery of prostacyclin remains the gold standard of treatment for patients presenting at NYHA class III to IV. 5,6 Currently, 2 prostacyclin formulations are registered for intravenous PAH treatment by the Food and Drug Administration (epoprostenol and treprostinil).…”

Prostacyclin Withdrawal in Pulmonary Hypertension #264

“…2 These drugs are administered via continuous parenteral infusion (IV; treprostinil can be given subcutaneously). Epoprostenol's half life is six minutes; 3 abrupt withdrawal can lead to significant symptom burden (dyspnea, anxiety, nausea, light-headedness, chest and abdominal pain) and rapid death.…”