title: Effects of the endothelin receptor antagonist bosentan on hemodynamics and exercise capacity in Japanese patients with mildly symptomatic pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension (PAH) trial has mostly enrolled patients with World Health Organization functional class (WHO FC) III or IV. However, PAH is rapidly progressive in nature even in patients with less severe forms at diagnosis. Following the recent studies in Western population, here we assessed the efficacy of bosentan in Japanese patients with WHO FCII PAH. In this open-label trial, bosentan 125 mg twice daily was administered for 12 weeks in 16 patients, and a hemodynamic evaluation was performed. Treatment was continued for a further 12 weeks, where the effect on exercise capacity was assessed in 13 patients. In 16 patients, mean pulmonary arterial pressure decreased from 40.4 ± 10.4 to 35.6 ± 12.6 mmHg (p = 0.018) and cardiac index increased from 2.54 ± 0.73 to 2.96 ± 0.82 L/min/m(2) (p = 0.023). Thus, pulmonary vascular resistance decreased from 792 ± 565 to 598 ± 558 dyn·sec/cm(5) (p = 0.006). In 13 patients followed up for 24 weeks, 6-min walking distance increased from baseline at Week 12 (p = 0.003) and Week 24 (p = 0.011). All patients were mildly symptomatic at baseline with dyspnea index (Borg scale) of 2.50 ± 1.58 and the specific activity scale (SAS) of 5.0 ± 1.4 METs. These values remained unchanged throughout the study. These results suggest that bosentan treatment was beneficial for Japanese patients with WHO FC II PAH and treatment should be started in the early stage of the disease.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. hatanoma@pg8.so-net.ne.jp.
authors.forename: Masaru
authors.initials: M
authors.lastname: Hatano
authors.affiliation: Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Yamada
authors.affiliation: Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Department of Cardiovascular Medicine, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Yoshioka
authors.affiliation: Department of Hematology and Rheumatology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Funauchi
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Kuwana
authors.affiliation: Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.affiliation: Division of Cardiology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: Division of Pulmonary Circulation, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Nakanishi
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization Ibaraki-Higashi National Hospital, Ibaraki, Japan.
authors.forename: Takefumi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Pediatrics, Toho University Omori Medical Center, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Saji
authors.affiliation: Kyoto University, Kyoto, Japan.
authors.forename: Shigetake
authors.initials: S
authors.lastname: Sasayama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D000077300:Bosentan; D065128:Endothelin Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D015444:Exercise; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013449:Sulfonamides / Q000008:administration & dosage* / Q000009:adverse effects; D014655:Vascular Resistance / Q000187:drug effects*; D055815:Young Adult
chemical_list: D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D000077300:Bosentan
keywords: Bosentan; Endothelin receptor antagonist; Hemodynamics; Pulmonary arterial hypertension; World Health Organization functional class