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).
Design and setting: Prospective, open label, uncontrolled study in a University Hospital in Brazil.
Population: 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).
Conclusion: 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.