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

Nobuhiro Tahara; Hiroaki Dobashi; Keiichi Fukuda; Masanori Funauchi; Masaru Hatano; Satoshi Ikeda; Shuji Joho; Yasuki Kihara; Takeshi Kimura; Takahisa Kondo; Masakazu Matsushita; Tohru Minamino; Norifumi Nakanishi; Yukio Ozaki; Tsutomu Saji; Satoshi Sakai; Nobuhiro Tanabe; Hiroshi Watanabe; Hidehiro Yamada; Koichiro Yoshioka; Shigetake Sasayama

doi:10.1253/circj.CJ-15-1305

Pulmonary Circulation

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

Nobuhiro Tahara, Hiroaki Dobashi, Keiichi Fukuda, Masanori Funauchi, Masaru Hatano, Satoshi Ikeda, Shuji Joho, Yasuki Kihara, Takeshi Kimura, Takahisa Kondo, Masakazu Matsushita, Tohru Minamino, Norifumi Nakanishi, Yukio Ozaki, Tsutomu Saji, Satoshi Sakai, Nobuhiro Tanabe, Hiroshi Watanabe, Hidehiro Yamada, Koichiro Yoshioka, Shigetake Sasayama

Author information

Nobuhiro Tahara
Department of Medicine, Division of Cardiovascular Medicine, Kurume University School of Medicine
Hiroaki Dobashi
Department of Internal Medicine, Division of Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University
Keiichi Fukuda
Department of Cardiology, Keio University School of Medicine
Masanori Funauchi
Department of Hematology and Rheumatology, Kindai University Faculty of Medicine
Masaru Hatano
Department of Cardiovascular Medicine, The Uiversity of Tokyo Hospital
Satoshi Ikeda
Department of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences
Shuji Joho
Second department of internal medicine, Toyama University Hospital
Yasuki Kihara
Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences
Takeshi Kimura
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University
Takahisa Kondo
Department of Advanced Medicine in Cardiopulmonary Disease, Nagoya University Graduate School of Medicine
Masakazu Matsushita
Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine
Tohru Minamino
Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences
Norifumi Nakanishi
Endowed Department of Pulmonary Hypertension and Pulmonary Vascular Medicine, National Cerebral and Cardiovascular Center Research Institute
Yukio Ozaki
Department of Cardiology, Fujita Health University Hospital
Tsutomu Saji
Department of Pediatrics, Toho University Omori Medical Center
Satoshi Sakai
Cardiovascular Division, Department of Clinical Medicine, Faculty of Medicine, University of Tsukuba
Nobuhiro Tanabe
Department of Respirology and Department of Advanced Medicine in Pulmonary Hypertension, Graduate School of Medicine, Chiba University
Hiroshi Watanabe
Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine
Hidehiro Yamada
Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine
Koichiro Yoshioka
Department of Cardiovascular Medicine, Tokai University School of Medicine
Shigetake Sasayama
Uji Hospital

Keywords: Endothelin receptor antagonist, Hemodynamics, Macitentan, Pulmonary arterial hypertension, Safety

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2016 Volume 80 Issue 6 Pages 1478-1483

DOI https://doi.org/10.1253/circj.CJ-15-1305

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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)

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