Bosentan for patients with chronic thromboembolic pulmonary hypertension

Vassallo, Fabio Giuseppe; Kodric, Metka; Scarduelli, Cleante; Harari, Sergio; Potena, Alfredo; Scarda, Angelo; Piattella, Marco; Cassandro, Roberto; Confalonieri, Marco

doi:10.1016/j.ejim.2008.03.008

« Previous Next »European Journal of Internal Medicine
Volume 20, Issue 1 , Pages 24-29, January 2009

Bosentan for patients with chronic thromboembolic pulmonary hypertension

Fabio Giuseppe Vassallo
- Department of Pneumology, University Hospital of Trieste, Trieste, Italy
Metka Kodric
- Department of Pneumology, University Hospital of Trieste, Trieste, Italy
Cleante Scarduelli
- Pneumology Unit, Hospital of Bozzolo-Mantova, Mantova, Italy
Sergio Harari
- Department of Pneumology, Hospital S.Giuseppe, Milan, Italy
Alfredo Potena
- Respiratory Unit, Arcispedale S.Anna, Ferrara, Italy
Angelo Scarda
- Department of Pneumology, University Hospital of Trieste, Trieste, Italy
Marco Piattella
- Respiratory Unit, Arcispedale S.Anna, Ferrara, Italy
Roberto Cassandro
- Department of Pneumology, Hospital S.Giuseppe, Milan, Italy
Marco Confalonieri
- Department of Pneumology, University Hospital of Trieste, Trieste, Italy
- Corresponding author. Department of Pulmonology (SC Pneumologia), University Hospital of Trieste, Strada di Fiume 447, 34100 Trieste, Italy. Tel.: +39 0403994665; fax: +39 0403994668.

Received 18 August 2007; received in revised form 28 November 2007; accepted 9 March 2008. published online 30 April 2008.

Abstract

Background

Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease leading to worsening functional status and reduced survival for those patients who cannot undergo pulmonary endarterectomy (PEA). Pharmacotherapy with novel drugs for pulmonary hypertension may be useful in treating patients who are poor candidates for surgery, but there are still few clinical data on medical therapy for CTEPH.

The aim of this prospective open-label, multicenter, study is to compare the efficacy of 1-year bosentan treatment to standard drugs in nonoperated patients with CTEPH.

Patients and methods

Thirty-four nonoperated patients with CTEPH were enrolled. Functional assessment included 6 minute walk test (6MWT), Borg index, WHO classification, arterial blood gases and echocardiography systolic pulmonary artery pressure (sPAP). Seventeen patients received bosentan (62.5 mg bid for 4 weeks and then 125 mg bid); 17 patients were treated with standard therapy alone.

Results

At admission sPAP was 76.18+/−5.96 mmHg in bosentan group and 71.48+/−3.71 mmHg in controls, p_aO₂ 64.68+/−2.25 mmHg in bosentan group, and 59.52+/−2.05 mmHg in controls, 6MWT 297.53+/−34.25 mt in bosentan group, and 268.47+/−36.54 mt in controls. After 12 months there were significant differences between the groups in the 6MWT (+57.24+/−22.21 m vs −73.13+/−21.23 m, p<0.001), dyspnoea index (Borg score 4.29+/−0.49 vs 7.06+/−0.32, p<0.001) and oxygenation (p_aO₂ 65.93+/−3.76 mmHg vs 48.48+/−1.31 mmHg, p<0.001). The sPAP was stable after 12 months of bosentan (76.18+/−5.96 mmHg vs 71.00+/−5.41 mmHg, p=0.221) in contrast to controls (71.48+/−3.71 mmHg vs 80.44+/−4.70 mmHg, p=0.029).

Conclusion

The data of this open-label study in nonoperated CTEPH patients suggest an improvement in functional outcomes adding Bosentan to diuretics and oral anticoagulants. No improvement was observed using only standard drugs after 1-year.

Keywords: Chronic thromboembolic pulmonary hypertension, Bosentan, Endothelin, Pulmonary hypertension, Thromboembolism, Six-minutes walking test