Long-term outcome in pulmonary arterial hypertension patients treated with subcutaneous treprostinil

Pulmonary arterial hypertension (PAH) is fatal if untreated. Intravenous epoprostenol improves exercise capacity and haemodynamics in PAH, and increases survival in idiopathic PAH (IPAH). To evaluate the effects of subcutaneous (SC) treprostinil, a longer-acting prostacyclin analogue, followed by the addition of other PAH therapies if needed, 860 PAH patients treated with SC treprostinil for up to 4 yrs were followed. Survival is reported as Kaplan–Meier estimates. For 332 IPAH patients with baseline haemodynamics, observed survival is also compared with predicted survival using the National Institute of Health formula. Out of the 860 patients, 199 (23%) discontinued due to adverse events, 136 (16%) died, 117 (14%) discontinued due to deterioration, 29 (3%) withdrew consent and 11 (1%) underwent transplantation. In total, 97 patients (11%) switched from SC treprostinil to an alternative prostacyclin analogue; bosentan was added in 105 patients (12%) and sildenafil in 25 (3%). In conclusion, survival was 87–68% over 1–4 yrs for all 860 patients and 88–70% over 1–4 yrs with subcutaneous treprostinil monotherapy. For the idiopathic pulmonary arterial hypertension subset with baseline haemodynamics (n = 332), survival was 91–72% over 1–4 yrs. In contrast, predicted survival was 69–38% over 1–4 yrs. The safety profile for long-term subcutaneous treprostinil was consistent with previous short-term trials with no unexpected adverse events.

[1]  R. Benza,et al.  Safety and efficacy of IV treprostinil for pulmonary arterial hypertension: a prospective, multicenter, open-label, 12-week trial. , 2006, Chest.

[2]  M. Humbert,et al.  Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension. , 2006, European heart journal.

[3]  R. Benza,et al.  Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary hypertension. , 2005, American Journal of Respiratory and Critical Care Medicine.

[4]  T. Fleming,et al.  Sildenafil citrate therapy for pulmonary arterial hypertension. , 2005, The New England journal of medicine.

[5]  A. Negassa,et al.  Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension. , 2005, European heart journal.

[6]  M. Humbert,et al.  Survival in patients with class III idiopathic pulmonary arterial hypertension treated with first line oral bosentan compared with an historical cohort of patients started on intravenous epoprostenol , 2005, Thorax.

[7]  M. Humbert,et al.  Long-Term Response to Calcium Channel Blockers in Idiopathic Pulmonary Arterial Hypertension , 2005, Circulation.

[8]  R. Barst,et al.  Erratum: "Survival with first-line bosentan in patients with primary pulmonary hypertension" (European Respiratory Journal (2005) vol. 25 (244-249)) , 2005 .

[9]  R. Barst,et al.  Survival with first-line bosentan in patients with primary pulmonary hypertension , 2005, European Respiratory Journal.

[10]  L. Rubin.  Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. , 2004, Chest.

[11]  L. Rubin,et al.  Introduction: New Insights Into a Challenging Disease A Review of the Third World Symposium on Pulmonary Arterial Hypertension , 2004 .

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

[13]  A. Shillington,et al.  Survival in Primary Pulmonary Hypertension: The Impact of Epoprostenol Therapy , 2002, Circulation.

[14]  Gilles Garcia,et al.  Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. , 2002, Journal of the American College of Cardiology.

[15]  W. Seeger,et al.  Inhaled iloprost for severe pulmonary hypertension. , 2002, The New England journal of medicine.

[16]  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.

[17]  Avid,et al.  BOSENTAN THERAPY FOR PULMONARY ARTERIAL HYPERTENSION , 2002 .

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

[19]  Inda,et al.  A COMPARISON OF CONTINUOUS INTRAVENOUS EPOPROSTENOL ( PROSTACYCLIN ) WITH CONVENTIONAL THERAPY FOR PRIMARY PULMONARY HYPERTENSION , 2000 .

[20]  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.

[21]  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.

[22]  S. Rich,et al.  The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. , 1992, The New England journal of medicine.

[23]  E H Bergofsky,et al.  Survival in Patients with Primary Pulmonary Hypertension: Results from a National Prospective Registry , 1991 .

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

[25]  V. Fuster,et al.  Primary pulmonary hypertension: natural history and the importance of thrombosis. , 1984, Circulation.