Two-years therapy with bosentan of pulmonary arterial hypertension related to connective tissue diseases]

Objective: Pulmonary arterial hypertension (PAH) is a rare but severe complication of connective tissue diseases (CTD), with a negative impact on patients survival. Bosentan, a receptor antagonist of endothelin, has been proved effective for the treatment of PAH. The aim of this study was to evaluate the effects and the safety of bosentan administered for 2 years in a group of patients with PAH related to CTD. Methods: Twelve patients with PAH related to systemic sclerosis (8 cases), SLE (2 cases), mixed connective tissue dis- ease (1 case) and polymyositis (1 case) attending the Rheumatology Unit of Padova University were treated with bosen- tan for two years. Distance walked in 6 minutes, right ventricular systolic pressure and mean pulmonary artery pres- sure estimated by doppler echocardiography were evaluated at baseline and after 6, 12, 18 and 24 months of treat- ment. Safety was assessed by laboratory tests performed every two months. Results: During bosentan treatment, a significant decrease of right ventricular systolic pressure was observed after 6, 12, 18 and 24 months in comparison to baseline, whereas pulmonary artery mean pressure remained unchanged. Dis- tance walked in 6 minutes slightly increased after 6 and 12 months, but significantly decreased after 18 and 24 months, mostly because complications of CTD which compromised the ability to walk arose in 4 patients. Adverse events re- lated to bosentan were observed in 2 cases. Conclusions: Bosentan has been demonstrated effective in reducing pulmonary arterial pressure in a two-year peri- od of treatment. Exercise capacity improved only in the first year of therapy and worsened thereafter, suggesting the opportunity of a combination therapy for a long-term treatment of PAH related to CTD