Transition from epoprostenol and treprostinil to the oral endothelin receptor antagonist bosentan in patients with pulmonary hypertension

Study objectives: Prior to the availability of the oral endothelin antagonist bosentan, most patients with pulmonary arterial hypertension (PAH) were treated with continuously infused prostacyclins. Many patients receiving prostacyclins would have received bosentan if it had been available at the time of their diagnosis. Noninvasive criteria (symptoms, World Health Organization [WHO] functional class, 6-min walk test [6MWT] distances, and echocardiograms) are used to govern up-titration of prostacyclins and to assess response to bosentan. The purposes of this study were to see if some patients might be able to transition safely from prostacyclin to bosentan, and whether noninvasive criteria could be used to monitor this transition. Methods: From January 2002 to July 2003, 23 stable patients with PAH attempted a transition from prostacyclin to bosentan over an 8-week period. 6MWT results, WHO class, and echocardiograms were recorded prior to transition and 1 month after successful transition. The transition was stopped and prostacyclin was resumed or up-titrated if any symptoms of PAH worsened. Results: Of 23 candidates (19 female and 4 male; age range, 17 to 73 years), 15 patients were transitioned to bosentan. Of these patients, four patients experienced worsening symptoms (range, 7 weeks to 12 months after cessation of prostacyclin) and resumed treatment with prostacyclin. Of the remaining 11 patients, 2 patients had liver function abnormalities 3 months and 10 months after transition to bosentan, respectively; 9 patients remained on bosentan 3 to 16 months after prostacyclin cessation. Patients failing transition and resuming prostacyclin returned to their pretransition functional baseline. Conclusion: Nine of 23 carefully selected, stable patients with PAH receiving long-term prostacyclin were successfully transitioned to oral bosentan using noninvasive monitoring. No long-term adverse events were associated with failed transition attempts. Further studies need to be carried out to determine which patients are more likely to undergo the transition successfully.