Continuous Subcutaneous Infusion of Treprostinil, a Prostacyclin Analogue, in Patients with Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension is a life-threatening disease for which continuous intravenous prostacyclin has proven to be effective. However, this treatment requires a permanent central venous catheter with the associated risk of serious complications such as sepsis, thromboembolism, or syncope. Treprostinil, a stable prostacyclin analogue, can be administered by a continuous subcutaneous infusion, avoiding these risks. We conducted a 12-week, double-blind, placebo-controlled multicenter trial in 470 patients with pulmonary arterial hypertension, either primary or associated with connective tissue disease or congenital systemic-to-pulmonary shunts. Exercise capacity improved with treprostinil and was unchanged with placebo; the between treatment group difference in median six-minute walking distance was 16 m (p = 0.006). Improvement in exercise capacity was greater in the sicker patients and was dose-related, but independent of disease etiology. Concomitantly, treprostinil significantly improved indices of dyspnea, signs and symptoms of pulmonary hypertension, and hemodynamics. The most common side effect attributed to treprostinil was infusion site pain (85%) leading to premature discontinuation from the study in 8% of patients. Three patients in the treprostinil treatment group presented with an episode of gastrointestinal hemorrhage. We conclude that chronic subcutaneous infusion of treprostinil is an effective treatment with an acceptable safety profile in patients with pulmonary arterial hypertension.

Inhaled iloprost for severe pulmonary hypertension

“…Similar results have been obtained with the use of other drugs for pulmonary hypertension, including epoprostenol, 30 beraprost, 31 and treprostinil. 28 Hemodynamic assessments of preinhalation values showed that values stabilized in the iloprost group, whereas they deteriorated in the placebo group. The degree of deterioration may be underestimated, since patients who discontinued treatment prematurely did not undergo follow-up hemodynamic examination.…”

“…2,28 Thus, targeted delivery of prostanoids to the pulmonary vasculature by means of inhalation may substantially reduce the drug requirements.…”

Guidelines for the diagnosis and treatment of pulmonary hypertension

“…Long-term persistence of efficacy has also been shown [79,97] can be accomplished by a microinfusion pump and a small subcutaneous catheter. The effects of treprostinil in PAH were studied in the largest worldwide RCT performed in this condition, and showed improvements in exercise capacity, haemodynamics and symptoms [128]. The greatest exercise improvement was observed in patients who were more compromised at baseline and in subjects who could tolerate the upper quartile dose (.…”

Pulmonary hypertension—“state of the art” management in 2012

“…46 There was statistically significant improvement in median exercise capacity, haemodynamics and clinical events compared to placebo group after 12 weeks of treatment with subcutaneous treprostinil. The effect was dose related.…”