Bosentan therapy of pulmonary arterial hypertension in connective tissue diseases

Abstract

Pulmonary arterial hypertension (PAH) is a life-threatening and debilitating complication of several connective tissue diseases. We aimed to evaluate the effects of long-term treatment with bosentan, an oral dual endothelin ET(A)/ET(B) receptor antagonist, in a cohort of patients with PAH related to connective tissue diseases. In the present prospective, noncontrolled study, 13 patients (nine with systemic sclerosis, two with systemic lupus erythematosus, one with mixed connective tissue disease and one with overlap syndrome including scleroderma and myositis), mostly nonresponders to prostanoids therapy, were treated for 1 year with bosentan. Cardiac haemodynamics and the diagnosis of PAH were performed by Doppler ultrasound examination. Exercise capacity was assessed by 6-min walking test at baseline and at 3, 6 and 12 months of therapy. During bosentan treatment, progressive improvement of exercise capacity was observed. Walk distance increased in seven patients, remained unchanged in three and slightly decreased in three patients. A progressive significant decrease of right ventricular systolic pressure was also observed, whereas pulmonary artery mean pressure remained unchanged. Adverse effects related to bosentan (elevation of hepatic aminotransferases) were noted in two patients. Long-term treatment with bosentan was effective in improving exercise capacity and pulmonary haemodynamics in patients with PAH related to connective tissue diseases.