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

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.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.At 2 months there was an improvement in 6MWD (p0.001) and functional class (p0.001) and a marked fall in PVR (p0.001), ICAM-1 (p0.001), IL-6 (p0.001)and BNP (p = 0.001). At 12 months, 6MWD was further improved (p0.001), PVR remained significantly improved (p0.001), mPAP was significantly decreased (p0.001) and ICAM-1, IL-6 and BNP remained significantly lower (p0.001). 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.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.