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 & 1 others Shigetake Sasayama

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 plasma N-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].).

Original languageEnglish
Pages (from-to)1478-1483
Number of pages6
JournalCirculation Journal
Volume80
Issue number6
DOIs
Publication statusPublished - 01-01-2016

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Pulmonary Hypertension
Safety
Vascular Resistance
Brain Natriuretic Peptide
Hemodynamics
Therapeutics
macitentan
Endothelin Receptor Antagonists
Biomarkers
Clinical Trials
Exercise

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Tahara, Nobuhiro ; Dobashi, Hiroaki ; Fukuda, Keiichi ; Funauchi, Masanori ; Hatano, Masaru ; Ikeda, Satoshi ; Joho, Shuji ; Kihara, Yasuki ; Kimura, Takeshi ; Kondo, Takahisa ; Matsushita, Masakazu ; Minamino, Tohru ; Nakanishi, Norifumi ; Ozaki, Yukio ; Saji, Tsutomu ; Sakai, Satoshi ; Tanabe, Nobuhiro ; Watanabe, Hiroshi ; Yamada, Hidehiro ; Yoshioka, Koichiro ; Sasayama, Shigetake. / Efficacy and safety of a novel endothelin receptor antagonist, macitentan, in japanese patients with pulmonary arterial hypertension. In: Circulation Journal. 2016 ; Vol. 80, No. 6. pp. 1478-1483.
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title = "Efficacy and safety of a novel endothelin receptor antagonist, macitentan, in japanese patients with pulmonary arterial hypertension",
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 plasma N-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].).",
author = "Nobuhiro Tahara and Hiroaki Dobashi and Keiichi Fukuda and Masanori Funauchi and Masaru Hatano and Satoshi Ikeda and Shuji Joho and Yasuki Kihara and Takeshi Kimura and Takahisa Kondo and Masakazu Matsushita and Tohru Minamino and Norifumi Nakanishi and Yukio Ozaki and Tsutomu Saji and Satoshi Sakai and Nobuhiro Tanabe and Hiroshi Watanabe and Hidehiro Yamada and Koichiro Yoshioka and Shigetake Sasayama",
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Tahara, N, Dobashi, H, Fukuda, K, Funauchi, M, Hatano, M, Ikeda, S, Joho, S, Kihara, Y, Kimura, T, Kondo, T, Matsushita, M, Minamino, T, Nakanishi, N, Ozaki, Y, Saji, T, Sakai, S, Tanabe, N, Watanabe, H, Yamada, H, Yoshioka, K & Sasayama, S 2016, 'Efficacy and safety of a novel endothelin receptor antagonist, macitentan, in japanese patients with pulmonary arterial hypertension', Circulation Journal, vol. 80, no. 6, pp. 1478-1483. https://doi.org/10.1253/circj.CJ-15-1305

Efficacy and safety of a novel endothelin receptor antagonist, macitentan, in japanese patients with pulmonary arterial hypertension. / Tahara, Nobuhiro; Dobashi, Hiroaki; Fukuda, Keiichi; Funauchi, Masanori; Hatano, Masaru; Ikeda, Satoshi; Joho, Shuji; Kihara, Yasuki; Kimura, Takeshi; Kondo, Takahisa; Matsushita, Masakazu; Minamino, Tohru; Nakanishi, Norifumi; Ozaki, Yukio; Saji, Tsutomu; Sakai, Satoshi; Tanabe, Nobuhiro; Watanabe, Hiroshi; Yamada, Hidehiro; Yoshioka, Koichiro; Sasayama, Shigetake.

In: Circulation Journal, Vol. 80, No. 6, 01.01.2016, p. 1478-1483.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Efficacy and safety of a novel endothelin receptor antagonist, macitentan, in japanese patients with pulmonary arterial hypertension

AU - Tahara, Nobuhiro

AU - Dobashi, Hiroaki

AU - Fukuda, Keiichi

AU - Funauchi, Masanori

AU - Hatano, Masaru

AU - Ikeda, Satoshi

AU - Joho, Shuji

AU - Kihara, Yasuki

AU - Kimura, Takeshi

AU - Kondo, Takahisa

AU - Matsushita, Masakazu

AU - Minamino, Tohru

AU - Nakanishi, Norifumi

AU - Ozaki, Yukio

AU - Saji, Tsutomu

AU - Sakai, Satoshi

AU - Tanabe, Nobuhiro

AU - Watanabe, Hiroshi

AU - Yamada, Hidehiro

AU - Yoshioka, Koichiro

AU - Sasayama, Shigetake

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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 plasma N-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].).

AB - 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 plasma N-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].).

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DO - 10.1253/circj.CJ-15-1305

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