Abstract 4384: Anti-Inflammatory Effects of Bosentan Therapy in Patients With Severe Pulmonary Arterial Hypertension
Objectives: Bosentan, is an oral, type A and B endothelin receptor antagonist which was first shown to improve exercise capacity and cardiopulmonary hemodynamics in patients (pts) with pulmonary arterial hypertension (PAH). We sought to investigate the short- and long- term anti-inflammatory effects of bosentan therapy in pts with severe PAH.
Methods: An open label study was performed in 15 pts (mean age 43±12.8 years, 8 male and 7 female) with severe primary PAH who were in NYHA III or IV, despite the conventional treatment. Pts received additional therapy with bosentan at the dosage of 62.5 mg twice daily for 4 weeks, followed by 125 mg twice daily for 11 months (m). Study endpoints included six-minute walking distance (6MWD), mean pulmonary artery pressure (mPA) and pulmonary vascular resistance (PVR), soluble endothelial adhesion molecules (ICAM-1 and VCAM-1) and interleukin-6 (IL-6). Pts were assessed at baseline, 2m and 12m after initiation of bosentan.
Results: At 2m, there was a significant improvement in 6MWD (p<0.01) and a marked fall in PVR (p<0.01). ICAM-1 and IL-6 were also significantly decreased compared to baseline (p<0.001). The 6MWD and PVR remained significantly improved (p<0.001) and PA was significantly decreased at 12m compared to baseline (p<0.01). Mean values of ICAM-1 and IL-6 remained significantly lower at 12m (Table⇓). A significant correlation was found between the reduction in PVR and IL-6 at 2 m (R=0.6, p<0.05)
Conclusions: Favourable anti-inflammatory effects of bosentan are mainly expressed within the first 2 m of therapy and they are associated with clinical and hemodynamic improvement. The sustained clinical and hemodynamic benefits of bosentan therapy could be attributed to its additional pleiotropic effects.