Prognostic factors associated with increased survival in patients with pulmonary arterial hypertension treated with subcutaneous treprostinil in randomized, placebo-controlled trials

J Heart Lung Transplant. 2011 Sep;30(9):982-9. doi: 10.1016/j.healun.2011.03.011. Epub 2011 May 4.


Background: Because of the challenges associated with conducting large survival studies of patients with pulmonary arterial hypertension (PAH), we analyzed the surrogate markers predictive of long-term survival in a large cohort of patients treated with subcutaneous treprostinil.

Methods: A retrospective review was conducted using data from a total of 811 patients with New York Heart Association Functional Class (NYHA FC) II to IV PAH, who were treated with subcutaneous treprostinil. Patient baseline disease and on-treatment parameters were analyzed by uni- and multivariate analyses for predictive value of 3-year survival with PAH.

Results: Among the baseline disease-related factors analyzed, there was a significantly higher risk of death (p < 0.001) associated with connective tissue disease-associated PAH relative to idiopathic PAH (hazard ratio for death [HR] 1.93), NYHA FC IV vs III (HR 2.31), pulmonary vascular resistance index (PVRI) >30 vs ≤16 mm Hg/liter/min/m(2) (HR 2.44) and mixed venous oxygen saturation (SVO(2)) ≤55% vs >55%. The 6-minute walk distance (6MWD) of ≤295 m after 12 weeks of treprostinil treatment was associated with reduced survival at 3 years (58%). A ≥20-m increase from baseline in 6MWD was associated with greater survival (80%) vs smaller walk increments (69%; p = 0.039). Treprostinil dose of ≥40 ng/kg/min (p < 0.001) and every 10-ng/kg/min dose increase (p = 0.009) resulted in improved long-term survival. In a multivariate analysis, only SVO(2), 6MWD and treprostinil dose were significant on-treatment predictors (p < 0.02) of survival.

Conclusions: Disease etiology, baseline factors (NYHA FC, PVRI and SVO(2)) and on-treatment factors (6MWD, SVO(2) and treprostinil dose) were predictors of survival in this study and may be used to aid in treatment optimization.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Epoprostenol / administration & dosage
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / therapeutic use
  • Familial Primary Pulmonary Hypertension
  • Female
  • Humans
  • Hypertension, Pulmonary / diagnosis
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / mortality*
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Retrospective Studies
  • Survival Rate
  • Treatment Outcome
  • Vascular Resistance / physiology
  • Young Adult


  • Antihypertensive Agents
  • Epoprostenol
  • treprostinil