Efficacy and Safety of a Novel Endothelin Receptor Antagonist, Macitentan, in Japanese Patients With Pulmonary Arterial Hypertension

• Tahara Nobuhiro

  Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine

• Dobashi Hiroaki

  Department of Internal Medicine, Division of Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University

• Fukuda Keiichi

  Department of Cardiology, Keio University School of Medicine

• Funauchi Masanori

  Department of Hematology and Rheumatology, Kindai University Faculty of Medicine

• Hatano Masaru

  Department of Cardiovascular Medicine, The Uiversity of Tokyo Hospital

• Ikeda Satoshi

  Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences

• Joho Shuji

  Second department of internal medicine, Toyama University Hospital

• Kihara Yasuki

  Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences

• Kimura Takeshi

  Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University

• Kondo Takahisa

  Department of Advanced Medicine in Cardiopulmonary Disease, Nagoya University Graduate School of Medicine

• Matsushita Masakazu

  Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine

• Minamino Tohru

  Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences

• Nakanishi Norifumi

  Endowed Department of Pulmonary Hypertension and Pulmonary Vascular Medicine, National Cerebral and Cardiovascular Center Research Institute

• Ozaki Yukio

  Department of Cardiology, Fujita Health University Hospital

• Saji Tsutomu

  Department of Pediatrics, Toho University Omori Medical Center

• Sakai Satoshi

  Cardiovascular Division, Department of Clinical Medicine, Faculty of Medicine, University of Tsukuba

• Tanabe Nobuhiro

  Department of Respirology and Department of Advanced Medicine in Pulmonary Hypertension, Graduate School of Medicine, Chiba University

• Watanabe Hiroshi

  Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine

• Yamada Hidehiro

  Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine

• Yoshioka Koichiro

  Department of Cardiovascular Medicine, Tokai University School of Medicine

• Sasayama Shigetake

  Uji Hospital

Abstract

Background:Macitentan is a novel, dual endothelin receptor antagonist with sustained receptor binding, used for the long-term treatment of pulmonary arterial hypertension (PAH). In the present study, we assessed the efficacy and safety of macitentan in Japanese patients with PAH.Methods and Results:Macitentan was administered at a once-daily dose of 10 mg in 30 patients. The primary endpoint was change in pulmonary vascular resistance (PVR) from baseline to week 24. Change to week 24 in the other hemodynamic parameters, 6-min walk distance (6MWD), World Health Organization (WHO) functional class, and plasmaN-terminal pro-brain natriuretic peptide (NT-pro-BNP), as well as time to clinical deterioration up to week 52 were also assessed as secondary endpoints. In the 28 patients on per-protocol analysis, PVR decreased from 667±293 to 417±214 dyn·sec·cm^–5(P<0.0001). 6MWD increased from 427±128 to 494±116 m (P<0.0001). WHO functional class improved in 13 patients (46.4%) and was maintained in 15 patients (53.6%), and NT-pro-BNP was reduced by 18% (P<0.0001). The favorable treatment effect on PVR was apparent regardless of concomitant therapy for PAH.Conclusions:Macitentan was efficacious and well tolerated and improved the hemodynamic parameters, exercise capacity, symptoms, and clinical biomarkers in Japanese PAH patients. Macitentan can be a valuable therapeutic option for Japanese patients with PAH. (Trial registration: JAPIC Clinical Trials Information [JapicCTI-121986].) (Circ J 2016; 80: 1478–1483)

Journal

• Circulation Journal

  Circulation Journal 80 (6), 1478-1483, 2016

  The Japanese Circulation Society

Keywords

• Endothelin receptor antagonist
• Hemodynamics
• Macitentan
• Pulmonary arterial hypertension
• Safety

Details

• CRID: 1390001205106883712
• NII Article ID: 130005153579
• NII Book ID: AA11591968
• DOI: 10.1253/circj.cj-15-1305
• ISSN: 13474820
• ISSN: 13469843
• NDL BIB ID: 027314829
• PubMed: 27180890
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I027314829
• Web Site: https://www.jstage.jst.go.jp/article/circj/80/6/80_CJ-15-1305/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2017055204
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • PubMed
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed