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      Selexipag for the treatment of chronic thromboembolic pulmonary hypertension

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          Abstract

          Background

          Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remain limited. Selexipag, an oral selective IP prostacyclin receptor agonist approved for pulmonary arterial hypertension, is a potential treatment option for CTEPH.

          Methods

          In this multicentre, randomised, double-blind, placebo-controlled study, 78 Japanese patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and/or balloon pulmonary angioplasty were randomly assigned to receive placebo or selexipag. The primary end-point was the change in pulmonary vascular resistance (PVR) from baseline to week 20. Secondary end-points were changes in other haemodynamic parameters: 6-min walk distance (6MWD), Borg dyspnoea scale score, World Health Organization (WHO) functional class, EuroQol five-dimension five-level tool and N-terminal pro-brain natriuretic peptide.

          Results

          The change in PVR was −98.2±111.3 dyn·s·cm −5 and −4.6±163.6 dyn·s·cm −5 in the selexipag and placebo groups, respectively (mean difference −93.5 dyn·s·cm −5; 95% CI −156.8 to −30.3; p=0.006). The changes in cardiac index (p<0.001) and Borg dyspnoea scale score (p=0.036) were also significantly improved over placebo. 6MWD and WHO functional class were not significantly improved. The common adverse events in the selexipag group corresponded to those generally observed following administration of a prostacyclin analogue.

          Conclusion

          Selexipag significantly improved PVR and other haemodynamic variables in patients with CTEPH, although exercise capacity remained unchanged. Further large-scale investigation is necessary to prove the role of selexipag in CTEPH.

          Abstract

          Selexipag significantly improved pulmonary vascular resistance and other haemodynamics in patients with chronic thromboembolic pulmonary hypertension, although exercise capacity remained unchanged https://bit.ly/3HfPA9s

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          Most cited references26

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          2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).

          Guidelines summarize and evaluate all available evidence on a particular issue at the time of the writing process, with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well as the risk-benefit ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate.
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            Selexipag for the Treatment of Pulmonary Arterial Hypertension.

            In a phase 2 trial, selexipag, an oral selective IP prostacyclin-receptor agonist, was shown to be beneficial in the treatment of pulmonary arterial hypertension.
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              Chronic thromboembolic pulmonary hypertension

              Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic PH leading to right heart failure and death. Lung ventilation/perfusion scintigraphy is the screening test of choice; a normal scan rules out CTEPH. In the case of an abnormal perfusion scan, a high-quality pulmonary angiogram is necessary to confirm and define the pulmonary vascular involvement and prior to making a treatment decision. PH is confirmed with right heart catheterisation, which is also necessary for treatment determination. In addition to chronic anticoagulation therapy, each patient with CTEPH should receive treatment assessment starting with evaluation for pulmonary endarterectomy, which is the guideline recommended treatment. For technically inoperable cases, PH-targeted medical therapy is recommended (currently riociguat based on the CHEST studies), and balloon pulmonary angioplasty should be considered at a centre experienced with this challenging but potentially effective and complementary intervention.
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                Author and article information

                Journal
                Eur Respir J
                Eur Respir J
                ERJ
                erj
                The European Respiratory Journal
                European Respiratory Society
                0903-1936
                1399-3003
                July 2022
                07 July 2022
                : 60
                : 1
                : 2101694
                Affiliations
                [1 ]Division of Advanced Medical Research in Pulmonary Hypertension, Division of Pulmonary Circulation, Dept of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Suita, Japan
                [2 ]Dept of Cardiology, National Hospital Organization Okayama Medical Centre, Okayama, Japan
                [3 ]Dept of Community Medicine Supporting System, Kyoto University Graduate School of Medicine, Kyoto, Japan
                [4 ]Dept of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan
                [5 ]Dept of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
                [6 ]Dept of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
                [7 ]Dept of Cardiology, Shinshu University School of Medicine, Matsumoto, Japan
                [8 ]Dept of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Japan
                [9 ]Dept of Cardiovascular Medicine, Kitasato University, Sagamihara, Japan
                [10 ]Dept of Cardiology, Yamaguchi Prefectural Grand Medical Centre, Hofu, Japan
                [11 ]Second Dept of Internal Medicine, University of Toyama, Toyama, Japan
                [12 ]Dept of Cardiology, The University of Tokyo Hospital, Tokyo, Japan
                [13 ]Cardiovascular Medicine, National Hospital Organization Kanazawa Medical Centre, Kanazawa, Japan
                [14 ]Dept of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan
                [15 ]Internal Medicine I, Hokkaido University Hospital, Sapporo, Japan
                [16 ]Dept of Cardiology, Tokai University School of Medicine, Isehara, Japan
                [17 ]Clinical Development Dept, Nippon Shinyaku Co., Ltd, Kyoto, Japan
                [18 ]Data Science Dept, Nippon Shinyaku Co., Ltd, Kyoto, Japan
                [19 ]Chibaken Saiseikai Narashino Hospital, Narashino, Japan
                [20 ]A list of study group members can be found in the supplementary material
                Author notes
                Corresponding author: Takeshi Ogo ( tak@ 123456ncvc.go.jp )
                Author information
                https://orcid.org/0000-0001-6719-1022
                https://orcid.org/0000-0001-9484-7912
                Article
                ERJ-01694-2021
                10.1183/13993003.01694-2021
                9260121
                34824052
                ffe48f68-29d8-453e-ad33-30189e644596
                Copyright ©The authors 2022.

                This version is distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0. For commercial reproduction rights and permissions contact permissions@ersnet.org

                History
                : 15 June 2021
                : 04 November 2021
                Funding
                Funded by: Nippon Shinyaku Co., Ltd
                Funded by: Janssen Pharmaceutical K.K.
                Categories
                Original Research Articles
                Pulmonary Hypertension
                7

                Respiratory medicine
                Respiratory medicine

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