American Journal of Cardiovascular Drugs

, Volume 18, Issue 2, pp 93–102 | Cite as

The Effect of Endothelin Receptor Antagonists in Patients with Eisenmenger Syndrome: A Systematic Review

  • Abdelrahman Elshafay
  • Duy Hieu Truong
  • Mohamed M. AboElnas
  • Hossam Idrees
  • Hatem G. Metwali
  • Nguyen Lam Vuong
  • Omar Ahmed Saad
  • Kenji Hirayama
  • Nguyen Tien Huy
Systematic Review



The efficacy of endothelin receptor antagonists (ERAs) in the management of Eisenmenger syndrome (ES) remains controversial. The aim of this study is to systemically review the safety and effects of ERAs in improving the quality of life and basic cardiac functions of these patients.


Twelve databases were searched, including PubMed, Web of Science, Scopus, Virtual Health Library, World Health Organization (WHO) Global Health Library, Google Scholar, POPLINE, Systems for Information of Grey Literature in Europe, New York Academy of Medicine,, metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform, through August 2016. We included randomized clinical trials addressing the effect of ERAs on cardiac functions in patients with ES. The quality of studies was assessed using the Cochrane Collaboration tool.


We included two trials represented by four papers, of which three papers reported the efficacy of bosentan against placebo and one paper reported the results of a combination of bosentan and sildenafil versus placebo and bosentan. One trial showed a significant effect of bosentan treatment over placebo on indexed pulmonary vascular resistance and mean pulmonary artery pressure, but a non-significant increase in 6-min walk distance and a non-significant effect on systemic pulse oximetry. The other trial reported the safe but non-significant effect of combination therapy of bosentan and sildenafil compared with bosentan and placebo.


This study demonstrated safety and improved hemodynamic effects of bosentan in ES, with a controversial effect on exercise capacity. Further randomized controlled trials with longer follow-up duration are needed to confirm these results.


Compliance with ethical standards


This study was supported in part by a “Grant-in-Aid for Scientific Research (B)” (16H05844, 2016–2019 for Nguyen Tien Huy) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, and by the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) (for Kenji Hirayama). The funders had no role in the study design, data collection and analysis, the preparation of the manuscript, or the decision to publish.

Conflict of interest

Abdelrahman Elshafay, Duy Hieu Truong, Mohamed M. AboElnas, Hossam Idrees, Hatem G. Metwali, Nguyen Lam Vuong, Omar Ahmed Saad, Kenji Hirayama, and Nguyen Tien Huy declare that they have no conflict of interest that might be relevant to the contents of this manuscript.

Supplementary material

40256_2017_240_MOESM1_ESM.docx (18 kb)
Supplementary material 1 (DOCX 17 kb)


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Faculty of MedicineAl-Azhar UniversityCairoEgypt
  2. 2.Quang Binh pharmaceutical joint-stock companyQuang BinhVietnam
  3. 3.Faculty of MedicineCairo UniversityCairoEgypt
  4. 4.Faculty of MedicineAssiut UniversityAssiutEgypt
  5. 5.Faculty of PharmacyAssiut UniversityAssiutEgypt
  6. 6.Department of Cardiovascular SurgeryUniversity Medical CenterHo Chi Minh CityVietnam
  7. 7.Department of Medical statistic and Informatics, Faculty of Public HealthUniversity of Medicine and PharmacyHo Chi Minh CityVietnam
  8. 8.Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Graduate School of Biomedical SciencesNagasaki UniversityNagasakiJapan
  9. 9.Evidence Based Medicine Research Group and Faculty of Applied SciencesTon Duc Thang UniversityHo Chi Minh CityVietnam
  10. 10.Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), Leading Graduate School Program, and Graduate School of Biomedical SciencesNagasaki UniversityNagasakiJapan

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