Chest
Volume 130, Issue 5, November 2006, Pages 1471-1480
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Original Research
Conversion to Bosentan From Prostacyclin Infusion Therapy in Pulmonary Arterial Hypertension: A Pilot Study

https://doi.org/10.1378/chest.130.5.1471Get rights and content

Study objectives

We assessed the efficacy of bosentan in transitioning from prostacyclin infusions in patients with pulmonary arterial hypertension (PAH).

Methods

Twenty-two PAH patients were recruited from five PAH centers if they had been clinically stable while receiving therapy with IV epoprostenol or subcutaneous treprostinil for at least 3 months. Patients were observed in an open-label prospective trial while bosentan was added to therapy, and then epoprostenol or treprostinil were tapered after 2 months.

Results

Ten of the 22 patients were transitioned off prostacyclin infusion therapy after a mean (± SEM) duration of 6.1 ± 1.2 months. Of those patients, seven patients have continued not receiving prostacyclin infusion therapy for a mean duration of 17.7 ± 5.3 months, with no significant changes in pulmonary artery (PA) pressure estimated by echocardiography, World Health Organization (WHO)/New York Heart Association (NYHA) functional class, 6-min walk distance (6MWD), or Borg dyspnea score. The conditions of three patients deteriorated, necessitating the resumption of prostacyclin therapy, and two patients subsequently died. Twelve patients failed to transition or even lower the prostacylin infusion rate and had worsening of their WHO/NYHA functional class and estimated systolic PA pressures, and had a trend toward deterioration in their mean 6MWD (294 ± 41 to 198 ± 34 m, respectively; p = 0.2). Of these, two patients subsequently died. The baseline characteristics of those who transitioned successfully vs those who transitioned unsuccessfully were a lower prostacyclin infusion rate, and less severe elevations in the mean and estimated systolic PA pressures.

Conclusion

Transitioning from therapy with prostacyclin to bosentan is possible in some PAH patients, mainly in those receiving lower prostacyclin doses and having less pulmonary hypertension at baseline. Careful patient selection and close interim monitoring is needed because the conditions of patients can deteriorate, and they may not respond to the resumption of therapy with prostacyclin.

Section snippets

Patients

The study was approved by the institutional review boards at all five participating PAH centers (ie, Tufts-New England Medical Center, Boston Medical Center, Rhode Island Hospital/Brown University, Massachusetts General Hospital, and Temple University) and was overseen by a data safety monitoring board. Patients with PAH receiving therapy either epoprostenol or treprostinil by continuous infusion were offered entry into the trial for potential transitioning to therapy with oral bosentan, and

Demographics

Twenty-two PAH patients were recruited from a total of 72 patients with PAH who were receiving prostacyclin therapy at five PAH centers. The remaining 50 patients either declined study entry (16 patients) or were not deemed sufficiently stable (34 patients) for study entry. As shown in Table 1, all enrolled patients were women (age range, 23 to 75 years; mean age, 49 ± 3 years) and predominately white. Comorbid conditions, time from diagnosis, and duration of PGI2 therapy prior to study

Discussion

Our open-label, multicenter pilot study demonstrates that transitioning from therapy with prostacyclin infusion to bosentan is possible in a minority of PAH patients (10 of 22 patients; 45%). Late failures to transition necessitating the resumption of prostacyclin therapy reduced the number of patients who remained successfully transitioned after 12 months to 7 of 22 (32%). Although transition was considered successful if the patient continued not to receive IV therapy, the lower mean 6MWD at 1

Conclusions

Although transitioning from infusion to oral therapy greatly enhances convenience and is desirable from the patient's perspective, our findings indicate that such a transition from therapy with infused prostacyclins to bosentan therapy is possible only in a minority of patients. In general, patients who are likely to transition successfully are receiving lower prostacyclin doses and have relatively mild PA pressure elevation, both at the time of diagnosis and at the time of transition. Patients

ACKNOWLEDGMENT

The authors are grateful to Arlene Schiro, NP, Anne Marie Kuzma, and Barbara S. Smithson, RN BSN, for their assistance in preparing the article.

References (19)

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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

Drs. Steiner and Criner have reported to the ACCP that they have no significant conflicts of interest with any companies/organizations whose products or services may be discussed in this article. Dr. Preston has reported receiving grants from Actelion, Cotherix, Encysive, Myogen, Pfizer, United Therapeutics, and ICOS-Lilly. Dr. Klinger has reported receiving grants from Actelion, Cotherix, Encysive, Myogen, Pfizer, ICOS-Lilly, and Sanofi-Aventis. Dr. Waxman has reported receiving grants from Actelion, Cotherix, Encysive, Myogen, Pfizer, United Therapeutics, ICOS-Lilly, and Predix. Dr. Farber has reported receiving grants from Actelion, Cotherix, Encysive, Myogen, Pfizer, ICOS-Lilly, and Predix. Dr. Hill has reported the following conflicts of interest: he has worked for the speakers bureau of Actelion; and he has received research grants from Actelion, Cotherix, Encysive, Myogen, Pfizer, United Therapeutics, ICOS-Lilly, and Predix.

This research was supported by Actelion Pharmaceuticals US, Inc, Ipswich, MA.

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