Bosentan for chronic thromboembolic pulmonary hypertension

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe and underdiagnosed disease characterized by progressive hypertension secondary to organized thrombi in pulmonary vessels. The arteriolar lesions of CTEPH are similar to those seen in idiopathic pulmonary arterial hypertension (PAH). Surgical disobliteration of the vessels by pulmonary endarterectomy is the therapy of choice but this is not suitable for all cases. To date, there is no licensed specific drug for CTEPH. Endothelin-1, a vasoconstrictor and promoter of cell proliferation, is involved in the pathogenesis of both CTEPH and PAH. Bosentan, the first oral dual endothelin receptor antagonist, has been shown to be effective in PAH. Preliminary uncontrolled and/or unblinded studies reported efficacy of bosentan in CTEPH, and the only randomized, controlled trials showed a positive hemodynamic effect but failed its other co-primary end point, namely the improvement of 6-min walking distance. Nevertheless, bosentan has been shown to be safe and the data from most literature encourage its use for inoperable CTEPH. However, further randomized controlled trials are needed to definitively establish bosentan as a standard drug for CTEPH.

Differentially Expressed Plasma MicroRNAs and the Potential Regulatory Function of Let-7b in Chronic Thromboembolic Pulmonary Hypertension

“…Endothelin receptor antagonists have emerged as cornerstone treatment for PAH for more than 10 years [47]. In CTEPH patients, especially inoperable ones, ETAs were also of benefit in hemodynamics [20]. ET-1 expression was a complex biological process.…”

“…ET-1 is a key vasoconstrictor especially in pulmonary circulation, and can cause proliferation of many cells involved in vascular remodeling. ET-1 level was elevated in CTEPH patients [18], and endothelin receptor antagonists (ETAs) have been applied for CTEPH treatment [20]. Transforming growth factor (TGF)-β plays important regulatory roles in the balance of cell proliferation and apoptosis.…”

Chronic Thromboembolic Pulmonary Hypertension: An Observational Study

“…For patients with CTEPH who have inoperable or persistent pulmonary hypertension after surgical treatment, the current ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension recommend the only currently approved drug treatment as follows: soluble guanylate cyclase activator, Riociguat [19,21]. Other drugs for pulmonary hypertension tested in CTEPH are used off-label [53][54][55][56][57][58][59][60][61][62]. Balloon pulmonary angioplasty (BPA) is an emerging and promising treatment option for CTEPH patients who have inoperable, segmental/subsegmental disease, or residual disease after pulmonary endarterectomy [63].…”

“…BPA continues to develop while future research is required to demonstrate the long-term benefits of the technique, standardize the method and define a uniform institutional infrastructure for providing BPA as a part of the treatment of CTEPH [63]. The choice to use off-label medications approved for PH and BPA can be taken into consideration in centers of expertise by a multidisciplinary team [53][54][55][56][57][58][59][60][61][62][63].…”