Galie N et al. (2006) Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation 114: 48–54

Eisenmenger syndrome is an advanced form of pulmonary arterial hypertension (PAH) related to congenital heart disease. Bosentan is a dual endothelin-1-receptor antagonist that effectively treats idiopathic PAH and PAH related to connective tissue disease. Following preliminary trials of bosentan for the treatment of Eisenmenger syndrome, the Bosentan Randomized Trial of Endothelin Antagonist Therapy-5 (BREATHE-5), was designed to confirm the drug's safety and efficacy.

Fifty-four patients with WHO functional class III Eisenmenger syndrome were randomized to receive therapy with either bosentan (n = 37) or placebo (n = 17). After 16 weeks of treatment, findings showed that bosentan did not compromise oxygen saturation. In addition, compared with placebo, bosentan therapy led to a decrease in pulmonary vascular resistance index (by 472.0 dynes/s/cm−5; P = 0.0383). Mean pulmonary arterial pressure was also diminished among patients treated with bosentan (by 5.5 mmHg; P = 0.0363), while their exercise capacity (as measure by 6 min walking distance) increased by 53.1 m (P = 0.008). A total of 18% of patients in the placebo group and 14% in the bosentan group had at least one serious adverse event.

These findings show that bosentan can improve the hemodynamics and exercise capacity of patients with Eisenmenger syndrome, without worsening peripheral levels of oxygen saturation. Furthermore, no unexpected adverse side effects were observed in patients who received bosentan therapy, and the profile of adverse events was comparable to that reported in other forms of PAH.