Bosentan: new preparation. Pulmonary hypertension: an option before epoprostenol infusion

(1) Pulmonary hypertension is a progressive disorder characterised by abnormally high pulmonary artery pressure, leading to right ventricular failure and death, generally after a few years. (2) Treatment usually combines an anticoagulant, oxygen therapy, a diuretic and, sometimes a calcium channel blocker. Efficacy is poorly documented but appears to be limited. Long-term treatment with epoprostenol (prostacyclin), given as a continuous intravenous infusion via a central catheter and pump improves the quality of life of patients with severe pulmonary hypertension (NYHA classes III and IV, associated with discomfort during daily activities or even at rest). The impact of this treatment on survival seems to depend on the type of pulmonary hypertension: benefits were seen in a trial in patients with idiopathic pulmonary hypertension, while there was no effect in another trial in patients with pulmonary hypertension associated with scleroderma. Epoprostenol causes numerous adverse effects, some of which can be severe. (3) Marketing authorisation was recently granted in Europe for oral bosentan therapy for pulmonary arterial hypertension severe enough to restrict daily activities. (4) Two placebo-controlled trials lasting 12 to 16 weeks included 32 and 213 patients who responded inadequately to calcium channel blockers. They showed that the 6-minute walking distance improved by a median of 76 metres and 44 metres, respectively. In the trial with 213 patients, 42% of patients in the bosentan group and 30% of those in the placebo group were improved according to the NHYA scale. No impact on survival was observed in these short trials. (5) A trial in 33 patients showed no difference in symptom improvement between groups treated with intravenous epoprostenol + oral bosentan or intravenous epoprostenol + oral placebo. (6) Two adverse effects require monitoring, namely anemia and elevated transaminase activity. Bosentan carries a risk of multiple pharmacokinetic interactions and is teratogenic in animals. Women taking bosentan cannot use hormone-based contraception, because of a pharmacokinetic interaction. (7) In practice, oral bosentan improves symptoms in patients whose daily activities are restricted by pulmonary arterial hypertension. Bosentan is easy to use, making it an option before continuous intravenous epoprostenol infusion, even though it may not be as effective.