Original articleBosentan for patients with chronic thromboembolic pulmonary hypertension
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
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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).
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Unfortunately, there are several patients with CTEPH who are not eligible for PEA.
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Data on alternative therapies to PEA for patients with inoperable CTEPH are limited in the literature.
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This study suggests bosentan as an effective treatment for nonoperated CTEPH patients.
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Medical Therapy Versus Balloon Angioplasty for CTEPH: A Systematic Review and Meta-Analysis
2018, Heart Lung and CirculationCitation Excerpt :Only one RCT which evaluated riociguat required independent adjudication of inoperability of disease as an eligibility criteria. Regarding uncontrolled observational studies of medical therapy, a total of 333 patients from 12 studies evaluated the effects of bosentan (n = 5) [24–28], sildenafil (n = 2) [29,30], beraprost (n = 1) [31], riociguat (n = 1) [32], intravenous epoprostenol (n = 2) [33,34], and subcutaneous treprostenil (n = 1) [35]. NYHA functional class III represented the majority of patients and prior PEA ranged from 0 to 32% of patients.
Use of outcome measures in pulmonary hypertension clinical trials
2015, American Heart JournalChronic thromboembolic pulmonary hypertension
2010, Clinics in Chest MedicineCitation Excerpt :In addition, the Bo-CTEPH study suggested quality-of-life improvements in a 6 month follow-up.92 An open-label, nonrandomized, placebo-controlled study by Vassallo and colleagues93 placed 17 patients with CTEPH on bosentan and 17 on placebo. They found statistically significant improvements in 6 MWD, Borg Dyspnea Index, and arterial partial pressure of oxygen (Pao2) in the bosentan treated cohort.
Bosentan for chronic thromboembolic pulmonary hypertension: Findings from a systematic review and meta-analysis
2010, Thrombosis ResearchCitation Excerpt :The weighted mean difference in the 6MWD at 3-6 months in these studies was 27.6 meters (95% CI 24.97 to 30.25), with a considerable standard deviation (Table 3). Four studies (54 patients) excluded post PEA patients [15,24,26,27]. In these studies the weighted mean difference in the 6MWD at 3-6 months was 64 meters (95% CI 61 to 67).