Safety and tolerability of bosentan in adults with Eisenmenger physiology

Background: Bosentan, a dual-endothelin receptor antagonist, is an established treatment for pulmonary arterial hypertension. We hypothesized that bosentan is safe and well tolerated in patients with Eisenmenger physiology. Methods: In this pilot open-label study, we primarily examined safety and tolerability of oral bosentan. Patients were recruited from our adult congenital heart clinic following informed consent. Baseline and 3-month assessment included WHO functional class, resting oxygen saturations, 6-min walk test, transthoracic echocardiography and respiratory mass spectrometry. Patient clinical status and liver enzymes were closely monitored throughout. Results: All 10 study patients (42 +/- 4 years; eight female) tolerated bosentan well. No major adverse events or significant liver enzyme elevations were observed. All but one patient felt better; none felt worse. Four patients experienced transient leg oedema. Resting oxygen saturations (83 +/- 5 versus 80 +/- 5%; P=0.011) and the distance travelled in the 6-min walk test (348 +/- 112 versus 249 +/- 117 m; P=0.004) increased relative to baseline. Changes in echocardiographic parameters (maximum aortic forward flow velocity 1.3 +/- 0.1 versus 1.1 +/- 0.2 ms, P=0.013; pulmonary arterial acceleration time 66 +/- 10 versus 58 +/- 12 m/s, P=0.02) and pulmonary blood flow (3.45 +/- 1.2 versus 2.58 +/- 1.0 L/min, P=0.008) suggested improved pulmonary haemodynamics by study end. Other echocardiographic changes suggested improved right ventricular systolic function (septal amplitude 1.0 versus 1.1 cm, P=0.048; systolic tissue Doppler velocity 4.8 versus 2.3 cm s(-1), P=0.002) by study end. Conclusions: Bosentan was safe and well tolerated in adults with Eisenmenger physiology both at initiation and after 3 months of oral therapy. Clinical status of patients and pulmonary haemodynamics appeared to improve, and this warrants further investigation. (C) 2004 Elsevier Ireland Ltd. All rights reserved.