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Gali\u00e8 N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, et al. 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). <i>Eur Heart J<\/i> 2016; 37: 67\u2013119.","DOI":"10.1093\/eurheartj\/ehv317"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Nergui S, Fukumoto Y, Do.e Z, Nakajima S, Shimizu T, Ikeda S, et al. Role of endothelial nitric oxide synthase and collagen metabolism in right ventricular remodeling due to pulmonary hypertension. <i>Circ J<\/i> 2014; 78: 1465\u20131674.","DOI":"10.1253\/circj.CJ-13-1586"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Dai Z, Sugimura K, Fukumoto Y, Tatebe S, Miura Y, Nochioka K, et al. Visualization of complete regression of pulmonary arterial remodeling on optical coherence tomography in a patient with pulmonary arterial hypertension. <i>Circ J<\/i> 2014; 78: 2771\u20132773.","DOI":"10.1253\/circj.CJ-14-0224"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. <i>N Engl J Med<\/i> 2004; 35: 1425\u20131436.","DOI":"10.1056\/NEJMra040291"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, et al. The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N\u2019-propylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist. <i>J Med Chem<\/i> 2012; 55: 7849\u20137861.","DOI":"10.1021\/jm3009103"},{"key":"6","doi-asserted-by":"publisher","unstructured":"6. Gatfield J, Mueller Grandjean C, Sasse T, Clozel M, Nayler O. Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells. <i>PLoS One<\/i> 2012; 7: e47662, doi:10.1371\/journal.pone.0047662.","DOI":"10.1371\/journal.pone.0047662"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Iglarz M, Landskroner K, Bauer Y, Vercauteren M, Rey M, Renault B, et al. Comparison of macitentan and bosentan on right ventricular remodeling in a rat model of non-vasoreactive pulmonary hypertension. <i>J Cardiovasc Pharmacol<\/i> 2015; 66: 457\u2013467.","DOI":"10.1097\/FJC.0000000000000296"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Pulido T, Adzerikho I, Channick RN, Delcroix M, Gali\u00e8 N, Ghofrani HA, et al. 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Bosentan therapy for pulmonary arterial hypertension. <i>N Engl J Med<\/i> 2002; 346: 896\u2013903.","DOI":"10.1056\/NEJMoa012212"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Channick RN, Simonneau G, Sitbon O, Robbins IM, Frost A, Tapson VF, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: A randomised placebo-controlled study. <i>Lancet<\/i> 2001; 358: 1119\u20131123.","DOI":"10.1016\/S0140-6736(01)06250-X"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Sasayama S, Kunieda T, Tomoike H, Matsuzaki M, Shirato K, Kuriyama T, et al. Effects of the endothelin receptor antagonist bosentan on hemodynamics, symptoms and functional capacity in Japanese patients with severe pulmonary hypertension. <i>Circ J<\/i> 2005; 69: 131\u2013137.","DOI":"10.1253\/circj.69.131"},{"key":"14","unstructured":"14. Sasayama S, Yoshida K, Izumiya K, Du M. Result of Japanese post-marketing surveillance of bosentan in pulmonary arterial hypertension. <i>Pharma Medica<\/i> 2013; 31: 151\u2013159 (in Japanese)."},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Sidharta PN, van Giersbergen PL, Halabi A, Dingemanse J. Macitentan: Entry-into-humans study with a new endothelin receptor antagonist. <i>Eur J Clin Pharmacol<\/i> 2011; 67: 977\u2013984.","DOI":"10.1007\/s00228-011-1043-2"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Chaumais MC, Guignabert C, Savale L, Ja\u00efs X, Boucly A, Montani D, et al. Clinical pharmacology of endothelin receptor antagonists used in the treatment of pulmonary arterial hypertension. <i>Am J Cardiovasc Drugs<\/i> 2015; 15: 13\u201326.","DOI":"10.1007\/s40256-014-0095-y"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Johnson JA. 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Population distribution and effects on drug metabolism of a genetic variant in the 5\u2019 promoter region of CYP3A4. <i>Clin Pharmacol Ther<\/i> 1999; 66: 288\u2013294.","DOI":"10.1016\/S0009-9236(99)70037-8"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Tateishi T, Watanabe M, Nakura H, Asoh M, Shirai H, Mizorogi Y, et al. CYP3A activity in European American and Japanese men using midazolam as an in vivo probe. <i>Clin Pharmacol Ther<\/i> 2001; 69: 333\u2013339.","DOI":"10.1067\/mcp.2001.115447"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Peacock AJ, Naeije R, Gali\u00e8 N, Rubin L. End-points and clinical trial design in pulmonary arterial hypertension: Have we made progress? <i>Eur Respir J<\/i> 2009; 34: 231\u2013242.","DOI":"10.1183\/09031936.00107108"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Gabler NB, French B, Strom BL, Palevsky HI, Taichman DB, Kawut SM, et al. Validation of 6-minute walk distance as a surrogate end point in pulmonary arterial hypertension trials. <i>Circulation<\/i> 2012; 126: 349\u2013356.","DOI":"10.1161\/CIRCULATIONAHA.112.105890"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. McLaughlin VV, Badesch DB, Delcroix M, Fleming TR, Gaine SP, Gali\u00e8 N, et al. End points and clinical trials design in pulmonary arterial hypertension. <i>J Am Coll Cardiol<\/i> 2009; 54: S97\u2013S107.","DOI":"10.1016\/j.jacc.2009.04.007"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Gali\u00e8 N, Simonneau G, Barst RJ, Badesch D, Rubin L. Clinical worsening in trials of pulmonary arterial hypertension: Results and implications. <i>Curr Opin Pulm Med<\/i> 2010; 16: S11\u2013S19.","DOI":"10.1097\/01.mcp.0000370206.61003.7e"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M, et al. Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension: Comparison with cardiopulmonary exercise testing. <i>Am J Respir Crit Care Med<\/i> 2000; 161: 487\u2013492.","DOI":"10.1164\/ajrccm.161.2.9906015"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27. Fattinger K, Funk C, Pantze M, Weber C, Reichen J, Stieger B, et al. The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: A potential mechanism for hepatic adverse reactions. <i>Clin Pharmacol Ther<\/i> 2001; 69: 223\u2013231.","DOI":"10.1067\/mcp.2001.114667"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28. Treiber A, \u00c4\u00e4nismaa P, de Kanter R, Delahaye S, Treher M, Hess P, et al. 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