title: Effect of bosentan treatment on surrogate markers in pulmonary arterial hypertension.
abstract: OBJECTIVE
  The aim of this study was to evaluate the effect of the oral dual ET(A)/ET(B) receptor antagonist bosentan on different surrogate markers in patients with pulmonary arterial hypertension (PAH).
  
  
  METHODS
  Prospective, open label, uncontrolled study in a University Hospital in Brazil.
  
  
  METHODS
  Fifteen PAH patients (11 females) with mean age of 40 +/- 11 years (5 in WHO functional class II, 10 in class III).
  
  
  METHODS
  All patients were investigated at baseline and after 16 weeks of bosentan treatment. We used the following surrogate markers for patients' evaluation: 6-min walk test, quality of life questionnaire (Short Form SF-36) and N-terminal proBNP (B type natriuretic peptide) fraction levels in blood.
  
  
  RESULTS
  Between the evaluation at baseline and week 16, the 6-min walk test distance changed from 396 +/- 135 to 434 +/- 137 m (p < 0.05). Each of the eight domains of the SF-36 was significantly improved. Mean NT-proBNP levels were decreased from a mean of 1670 pg/mL to 1010 pg/mL (p = 0.01).
  
  
  CONCLUSIONS
  The study suggests that bosentan treatment results in the improvement of different kinds of surrogate markers independently of their specificity to reflect functional capacity, quality of life and myocardial stress. It is concluded that the combined use of these different markers may be an alternative endpoint for future short duration clinical trials.
authors.affiliation: Pulmonary Division, Pulmonary Hypertension Unit, Heart Institute, University of São Paulo Medical School, São Paulo, Brazil. rgrsz@uol.com.br
authors.forename: Rogerio
authors.initials: R
authors.lastname: Souza
authors.forename: Carlos
authors.initials: C
authors.lastname: Jardim
authors.forename: Bárbara
authors.initials: B
authors.lastname: Martins
authors.forename: Felipe
authors.initials: F
authors.lastname: Cortopassi
authors.forename: Mateo
authors.initials: M
authors.lastname: Yaksic
authors.forename: Rogerio
authors.initials: R
authors.lastname: Rabelo
authors.forename: Humberto
authors.initials: H
authors.lastname: Bogossian
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D000077300:Bosentan; D001938:Brazil; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D011446:Prospective Studies; D011788:Quality of Life; D013449:Sulfonamides / Q000627:therapeutic use*; D011795:Surveys and Questionnaires; D016138:Walking
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D013449:Sulfonamides; D020097:Natriuretic Peptide, Brain; D000077300:Bosentan