title: Treatment of Pulmonary Arterial Hypertension Using Initial Combination Therapy of Bosentan and Iloprost.
abstract: BACKGROUND
  Monotherapy and sequential combination therapy have been widely used in the treatment of pulmonary arterial hypertension (PAH). There is limited evidence for initial combination therapy in patients with PAH, particularly those with World Health Organization (WHO) functional class III or IV.
  
  
  METHODS
  Twenty-seven consecutive treatment-naive PAH subjects with WHO functional class III or IV PAH were randomized into 3 groups with a 1:1:1 ratio: a combination therapy group with 125 mg of bosentan twice daily plus 10 μg of iloprost 4-6 times/d; a bosentan monotherapy group with 125 mg of bosentan twice daily; and a iloprost monotherapy group with 10 μg of iloprost 4-6 times/d. Clinical and hemodynamic data were collected at baseline, 6 weeks, and 3 months. The primary end point was the change in the 6-min walk distance (6MWD) from baseline values.
  
  
  RESULTS
  At baseline, there were no differences in demographics, WHO classification, hemodynamics, classification of PAH, or 6MWD among the 3 groups. The 6MWD significantly improved in the combination therapy group compared with the bosentan monotherapy and iloprost monotherapy groups at week 6 (P= .001) and after 3 months (P< .001), respectively. Secondary end points significantly improved in the combination therapy group for mean pulmonary artery pressure, cardiac index, and WHO functional classification after 3 months of treatment and for N-terminal pro-brain natriuretic peptide, Minnesota Living with Heart Failure questionnaire scores, and PaO2after 6 weeks and 3 months of treatment, compared with the monotherapy groups.
  
  
  CONCLUSIONS
  Initial combination therapy in treatment-naive PAH subjects with WHO functional class III or IV can significantly improve 6MWD, hemodynamics, and quality of life compared with monotherapy. Further studies with large samples and placebo controls are required to assess the tolerability and efficacy of initial combination therapy in patients with PAH. (ClinicalTrials.gov registration NCT01712997).
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xinpeng
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Medical Statistics, Fourth Military Medical University, Xi'an, China.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Respiratory Medicine, The Fourth People's Hospital of Shaanxi Province, Xi'an, China.
authors.forename: Liying
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Respiratory Medicine, Xi'an Aerospace General Hospital, Xi'an, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Niu
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Xuemin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Shuoyao
authors.initials: S
authors.lastname: Qu
authors.affiliation: Department of Respiratory Medicine, Huashan Hospital, Fudan University, Shanghai, China. shengqingli@hotmail.com.
authors.forename: Shengqing
authors.initials: S
authors.lastname: Li
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D000077300:Bosentan; D004359:Drug Therapy, Combination; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D016285:Iloprost / Q000008:administration & dosage*; D008297:Male; D011651:Pulmonary Artery / Q000503:physiopathology; D011788:Quality of Life; D013449:Sulfonamides / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage*; D000070857:Walk Test
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D014665:Vasodilator Agents; D016285:Iloprost; D000077300:Bosentan
keywords: 6-min walk distance; bosentan; combination therapy; iloprost; pulmonary arterial hypertension