Chest
Volume 126, Issue 3, September 2004, Pages 808-815
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Clinical Investigations
PULMONARY VASCULAR DISEASE
Transition From Epoprostenol and Treprostinil to the Oral Endothelin Receptor Antagonist Bosentan in Patients With Pulmonary Hypertension

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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.

Section snippets

Patient Selection

Patients with PAH receiving prostacyclin who wanted to transition from parenteral prostacyclin were assessed for the potential transition to oral bosentan. Patients selected as appropriate for this transition had to demonstrate stability, defined as the need for infrequent (once or less per month) increases in prostaglandin dose, WHO functional class II or III, and with no clinical evidence of heart failure (ie, jugular venous distension, pulsatile liver, lower-extremity edema, etc.). Patients

Results

Twenty-three stable patients with PAH in WHO class II and III receiving continuous prostacyclin infusion attempted transition to oral bosentan. Patient demographics are shown in Table 1. The patients were predominantly female (19 of 23 patients), and PPH was the predominant diagnosis. Seventeen patients were receiving epoprostenol (10 to 76 ng/kg/min; mean dose, 36 ng/kg/min), and 6 patients were receiving treprostinil (28 to 150 ng/kg/min; mean dose, 79 ng/kg/min).

Of the original 23 patients,

Discussion

There is a single, recent article13 that reports successful cessation of epoprostenol in three patients who experienced normalization of their PAPs following years of prostacyclin therapy. This article, from one of the largest pulmonary hypertension centers in the United States, demonstrates the rarity of this occurrence. In contrast, the risk of sudden death with prostacyclin interruption is well recognized. There have been no published studies to date demonstrating safe and effective

Conclusion

A significant number of patients with PAH receiving continuous prostacyclin therapy can be effectively and safely transitioned to oral bosentan, thereby reducing the burden of adverse effects experienced by patients due to prostacyclin therapy and the delivery systems. This transition can be successfully and safely achieved using noninvasive monitoring. Patients who were transitioned in this study were carefully selected and had stable disease. Based on this small study, there does not appear

ACKNOWLEDGMENT

We thank Jan Schneider, RN, and Helena Purl, RN, for their assistance in compiling the data for this study.

References (13)

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This work was supported by a research grant from the Frueauff Foundation.

This work was presented in poster form at the American Thoracic Society International Conference 2003, May 16–21, 2003, Seattle, WA, and the presenter was supported by a travel grant from Actelion.

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