Short and long term anti-inflammatory effects of bosentan therapy in patients with pulmonary arterial hypertension: relation to clinical and hemodynamic responses

Abstract

Objective: We sought to investigate the short- and long- term effects of bosentan therapy on endothelial, inflammatory and fibrotic markers in patients with pulmonary arterial hypertension (PAH) and the relation to clinical and hemodynamic responses.Methods: We studied 16 patients with moderate-severe idiopathic PAH, in WHO functional class II-IV, despite conventional treatment. Patients received additional treatment with bosentan, 62.5 mg twice daily for 1 month, followed by 125 mg twice daily for 11 months. Study endpoints included 6-min walking distance (6MWD), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and plasma levels of intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), IL-6 and brain natriuretic peptide (BNP). Patients were assessed at baseline, 2 months and 12 months after initiation of bosentan.Results: At 2 months there was an improvement in 6MWD (p < 0.001) and functional class (p < 0.001) and a marked fall in PVR (p < 0.001), ICAM-1 (p < 0.001), IL-6 (p < 0.001)and BNP (p = 0.001). At 12 months, 6MWD was further improved (p < 0.001), PVR remained significantly improved (p < 0.001), mPAP was significantly decreased (p < 0.001) and ICAM-1, IL-6 and BNP remained significantly lower (p < 0.001). Significant correlations were found between changes in ICAM-1 and cardiac index (r = 0.59, p = 0.01), IL-6 and PVR (r = 0.51, p = 0.04), BNP and 6MWD (r = −0.53, p = 0.03) and BNP and PAP (r = 0.51, p = 0.04) between 2- and 12-months treatment.Conclusions: In patients with moderate-severe PAH, the addition of bosentan to therapy, exerts favorable anti-inflammatory effects, which are associated with clinical and hemodynamic improvement.