Chest
Volume 128, Issue 4, October 2005, Pages 2363-2367
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Clinical Investigations
Bosentan Therapy for Inoperable Chronic Thromboembolic Pulmonary Hypertension

https://doi.org/10.1378/chest.128.4.2363Get rights and content

Study objectives

We performed an open-label multicenter study to evaluate the safety and efficacy of the dual endothelin receptor antagonist bosentan in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).

Patients

Nineteen patients with inoperable CTEPH were enrolled.

Measurements

The primary end point was a change in pulmonary vascular resistance (PVR). Secondary end points included 6-min walk test, peak oxygen uptake ( V˙ o2), New York Heart Association functional class, serum levels of N-terminal-pro brain natriuretic peptide (NT-pro-BNP), and various other hemodynamic parameters.

Results

After 3 months of treatment with bosentan, PVR decreased from 914 ± 329 to 611 ± 220 dyne·s·cm−5 (p < 0.001). Functional class and peak V˙ o2 remained unchanged, but 6-min walk distance increased from 340 ± 102 to 413 ± 130 m (p = 0.009), and serum NT-pro BNP levels improved from 2,895 ± 2,620 to 2,179 ± 2,301 (p = 0.027). One patient died, presumably from influenza A infection, and another patient experienced progressive fluid retention despite reduction of PVR. Other than that, treatment was well tolerated by all patients.

Conclusions

This open-label pilot trial suggests that bosentan may offer a therapeutic option for patients with inoperable CTEPH. Randomized controlled trials are warranted to confirm these findings.

Section snippets

Patient Selection

In order to ensure diagnostic accuracy and to prevent inclusion of patients with operable disease, this study was carried out at the three largest referral centers for surgical treatment of CTEPH in Germany. All patients underwent standardized assessment at the centers including ventilation/perfusion scanning, helical CT of the chest, and pulmonary angiography. The final decision to classify the patient as inoperable was made together with the surgeon in charge of the PEA program. Patients who

Results

Between September 2003 and June 2004, 19 patients were enrolled into this study. Four patients had persistent/recurrent pulmonary hypertension after previous PEA (1.5 years, 4 years, 5 years, and 6 years after surgery, respectively); the others had nonoperable CTEPH. The interval between diagnosis of CTEPH and study entry was > 3 months in all patients and was > 12 months in 10 patients. All patients had received adequate treatment with oral anticoagulants since diagnosis. Demographics,

Discussion

This open-label pilot trial, despite limited by its relatively small sample size and its uncontrolled design, shows that the dual endothelin receptor antagonist bosentan may have beneficial effects in selected patients with inoperable CTEPH. On first glance, it may seem counterintuitive to use a vasoactive treatment in a disease that is characterized by mechanical obstruction of pulmonary vessels. However, several lines of evidence suggest that, after the initializing event of single, multiple,

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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).

The present study was funded by Actelion Pharmaceuticals, the manufacturer of bosentan.

Dr. Hoeper and Dr. Wilkens have received speaker's honorariums from Actelion Pharmaceuticals. Dr. Hoeper serves as an Advisory Board Member for Actelion Pharmaceuticals.

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