Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension.

RATIONALE Intravenous epoprostenol improves exercise capacity and survival in patients with pulmonary arterial hypertension. The prostacyclin analog treprostinil is also efficacious by subcutaneous infusion, is easier to administer, and has a longer half-life. With the demonstration of bioequivalence between subcutaneous and intravenous treprostinil, intravenous treprostinil may have an overall better risk-benefit profile than intravenous epoprostenol. OBJECTIVE To evaluate the safety and efficacy of transitioning patients with pulmonary arterial hypertension from intravenous epoprostenol to intravenous treprostinil. METHODS Patients enrolled in a 12-wk prospective open label study were switched from intravenous epoprostenol to intravenous treprostinil over 24 to 48 h. The intravenous treprostinil dose was adjusted to minimize symptoms/side effects. RESULTS Thirty-one patients (mean age, 43 yr; 22 women) were enrolled. Twenty-seven patients completed the protocol; 4 patients transitioned back to epoprostenol. Six-minute walk distance (n = 27; baseline, 438 +/- 16 m; Week 12, 439 +/- 16 m), Naughton-Balke treadmill test time (n = 26; baseline, 582 +/- 50 s; Week 12, 622 +/- 48 s), functional class, and Borg score were maintained with intravenous treprostinil at Week 12 versus intravenous epoprostenol before transition. At Week 12, mean pulmonary artery pressure increased 4 +/- 1 mm Hg (n = 27, p < 0.01), cardiac index decreased 0.4 +/- 0.1 L/min/m2 (n = 27, p = 0.01), and pulmonary vascular resistance increased 3 +/- 1 Wood units x m2 (n = 26, p < 0.01). No serious adverse events were attributed to treprostinil. CONCLUSIONS These data suggest that transition from intravenous epoprostenol to intravenous treprostinil is safe and effective; whether the hemodynamic differences associated with intravenous treprostinil are clinically important requires longer follow-up.

[1]  T. Hunt,et al.  Pharmacokinetics and Steady-State Bioequivalence of Treprostinil Sodium (Remodulin®) Administered by the Intravenous and Subcutaneous Route to Normal Volunteers , 2004, Journal of cardiovascular pharmacology.

[2]  S. Rich,et al.  Efficacy and Safety of Treprostinil: An Epoprostenol Analog for Primary Pulmonary Hypertension , 2003, Journal of cardiovascular pharmacology.

[3]  S. Rich,et al.  Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. , 2002, American journal of respiratory and critical care medicine.

[4]  Stuart Rich,et al.  Continuous Intravenous Epoprostenol for Pulmonary Hypertension Due to the Scleroderma Spectrum of Disease , 2000, Annals of Internal Medicine.

[5]  M. Humbert,et al.  Short-term and long-term epoprostenol (prostacyclin) therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study , 1999 .

[6]  R. Barst,et al.  Long-term prostacyclin for pulmonary hypertension with associated congenital heart defects. , 1999, Circulation.

[7]  M. Humbert,et al.  Treatment of pulmonary hypertension secondary to connective tissue diseases , 1999, Thorax.

[8]  S. Rich,et al.  Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. , 1998, The New England journal of medicine.

[9]  B. Groves,et al.  A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. , 1996, The New England journal of medicine.

[10]  J. Sailstad,et al.  The pharmacokinetics and pharmacodynamics of the prostacyclin analog 15AU81 in the anesthetized beagle dog. , 1993, Prostaglandins, leukotrienes, and essential fatty acids.

[11]  M. Mata,et al.  The effects of 15AU81, a chemically stable prostacyclin analog, on the cardiovascular and renin-angiotensis systems of anesthetized dogs , 1991 .

[12]  B. Molony,et al.  Intravenous Infusion of Prostacyclin Sodium in Man: Clinical Effects and Influence on Platelet Adenosine Diphosphate Sensitivity and Adenosine 3′:5′‐Cyclic Monophosphate Levels , 1981, Circulation.