title: Prognostic factors associated with increased survival in patients with pulmonary arterial hypertension treated with subcutaneous treprostinil in randomized, placebo-controlled trials.
abstract: 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.
authors.affiliation: Division of Cardiovascular Diseases, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212, USA. rbenza@wpahs.org
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Benza
authors.forename: Mardi
authors.initials: M
authors.lastname: Gomberg-Maitland
authors.forename: Robert
authors.initials: R
authors.lastname: Naeije
authors.forename: Carl P
authors.initials: CP
authors.lastname: Arneson
authors.forename: Irene M
authors.initials: IM
authors.lastname: Lang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000502:physiology; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D011464:Epoprostenol; C427248:treprostinil