title: Baseline NT-proBNP correlates with change in 6-minute walk distance in patients with pulmonary arterial hypertension in the pivotal inhaled treprostinil study TRIUMPH-1.
abstract: BACKGROUND
  N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a biomarker of disease severity in pulmonary arterial hypertension (PAH). In this study we aimed to determine whether baseline NT-proBNP levels correlate with improvement in 6-minute walk distance (6MWD) in the pivotal randomized, placebo-controlled, double-blind study of the addition of inhaled treprostinil to oral therapy for PAH.
  
  
  METHODS
  A post hoc analysis of data from the TRIUMPH-1 study was performed in patients who had assessments of NT-proBNP levels and baseline and Week 12 6MWD. Least-squares mean analysis was used to compare patients in the highest quartile of baseline NT-proBNP with those in lower quartiles with regard to change from baseline in 6MWD, stratified by treatment.
  
  
  RESULTS
  The NT-proBNP within-treatment median changes from baseline to Week 12 were +44 and -72 pg/ml, and the median changes in 6MWD from baseline to Week 12 were +5 and +40 m for the placebo (n = 94) and inhaled treprostinil (n = 84) groups, respectively. Baseline NT-proBNP levels demonstrated a strong interaction with treatment in predicting change from baseline for 6MWD (p < 0.01), indicating that, in the upper quartile (≥1,513.5 pg/ml), patients on inhaled treprostinil had a better response (+64 vs +32 m), whereas patients on placebo fared worse (-13 vs +20 m) when compared with the lower 3 quartiles (<1,513.5 pg/ml). Furthermore, least-squares mean difference in 6MWD between active and placebo groups was +67 and +16 m for the upper and lower 3 quartiles of NT-proBNP, respectively.
  
  
  CONCLUSIONS
  Greater improvement in 6MWD in actively treated patients with high levels of NT-proBNP enhances understanding of the robustness of clinical response to inhaled treprostinil in more advanced disease.
authors: Division of Cardiovascular Diseases, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. frantz.robert@mayo.edu
authors: Robert P
authors: RP
authors: Frantz
authors: Susanne
authors: S
authors: McDevitt
authors: Susan
authors: S
authors: Walker
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology*; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D011464:Epoprostenol; C427248:treprostinil