Effect of bosentan treatment on surrogate markers in pulmonary arterial hypertension.
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.
Souza
Rogerio
R
Pulmonary Division, Pulmonary Hypertension Unit, Heart Institute, University of São Paulo Medical School, São Paulo, Brazil. rgrsz@uol.com.br
Jardim
Carlos
C
Martins
Bárbara
B
Cortopassi
Felipe
F
Yaksic
Mateo
M
Rabelo
Rogerio
R
Bogossian
Humberto
H
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
D000959:Antihypertensive Agents; D015415:Biomarkers; D013449:Sulfonamides; D020097:Natriuretic Peptide, Brain; D000077300:Bosentan