Original article
Bosentan for patients with chronic thromboembolic pulmonary hypertension

https://doi.org/10.1016/j.ejim.2008.03.008Get rights and content

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, paO2 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 (paO2 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.

Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) is a major although underdiagnosed cause of progressive elevation of pulmonary arterial pressure and vascular resistances, ultimately leading to right ventricular dysfunction and death [1], [2], [3].

Vascular re-canalization by pulmonary endarterectomy (PEA) is the elective treatment when the thrombi are accessible and there is no serious concomitant lung disease, but not all the patients are eligible for surgery [4]. Nonoperated patients are usually treated only with oral anticoagulation, diuretics and supplemental oxygen for hypoxemia with poor results [5], [6], [7], although generally progression to death is more slowly than idiopathic pulmonary hypertension [8]. The availability of novel drugs for pulmonary hypertension may represent a useful therapeutic alternative in treating patients who are poor candidates for surgery, but there are still few clinical data on pharmacotherapy, most of them from retrospective and uncontrolled studies [9].

The aim of this prospective, multicentre, open-label study is to compare the one-year efficacy of bosentan plus standard therapy to standard therapy alone in patients with inoperable CTEPH.

Section snippets

Setting

The multicenter study was conducted in four Pulmonary Hospital Units in Northern Italy (Department of Pulmonology, University Hospital, Trieste; Department of Pulmonology, San Giuseppe Hospital, Milan, Department of Pulmonology, General Hospital, Mantova; Department of Respiratory Disease, University Hospital, Ferrara) in the period from March 2005 to March 2007.

Study design and diagnostic procedures

This open-label, prospective, nonrandomized study enrolled consecutive symptomatic patients with inoperable CTEPH and WHO class [8] II

Results

Seventy-one patients with secondary pulmonary hypertension were diagnosed during the study period. Thirty-three patients were excluded from the study by other diseases known to cause secondary hypertension: 10 patients had COPD, 8 patients had connective tissue disease, 1 patient had congenital heart disease, 9 patients had idiopathic pulmonary fibrosis, 1 patient with sarcoidosis. Other 9 patients were excluded by the study because they were found suited for PEA. Thirty-four patients with

Discussion

The results of our study suggest that nonoperated patients with CTEPH could benefit treatment with bosentan plus conventional therapy. In fact, 1-yr bosentan therapy seems to slow the functional deterioration and disease progression in CTEPH patients whilst medical conventional therapy alone did not. Only the bosentan therapy improved 6-min walking distance, oxygenation, Borg dyspnea index, and WHO functional class, whilst the not-bosentan cohort did not improve after 1-year. Bosentan was well

Learning points

  • Chronic thromboembolic pulmonary artery hypertension (CTEPH) is a progressive disease leading to worsening functional status and reduced survival to those patients who cannot undergo surgical pulmonary endarterectomy (PEA).

  • Unfortunately, there are several patients with CTEPH who are not eligible for PEA.

  • Data on alternative therapies to PEA for patients with inoperable CTEPH are limited in the literature.

  • This study suggests bosentan as an effective treatment for nonoperated CTEPH patients.

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