title: Long-term outcome of bosentan treatment in idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension associated with the scleroderma spectrum of diseases.
abstract: BACKGROUND
  Bosentan improves clinical outcomes in pulmonary arterial hypertension (PAH), particularly in the idiopathic (IPAH) subset. Scant data are available regarding PAH associated with the scleroderma spectrum of diseases (APAH-SSD). Here we review our experience with bosentan in these 2 groups.
  
  
  METHODS
  Included were all patients at our center with either IPAH or APAH-SSD in whom bosentan was the first-line, single-agent therapy with at least 6 months of follow-up. Changes in the World Health Organization (WHO) functional class from baseline to the most recent follow-up on monotherapy were compared between the 2 groups, as well as overall survival and time to a composite end point of hepatotoxicity requiring discontinuation, use of additional therapy, or death.
  
  
  RESULTS
  Nineteen IPAH and 17 APAH-SSD subjects with similar baseline clinical characteristics and a median follow-up 9 months (range, 6-44) were analyzed. In IPAH subjects, WHO class improved from 3.1 +/- 0.5 at baseline to 2.4 +/- 0.8 (p = 0.005). No change occurred in the APAH-SSD group: 2.9 +/- 0.3 vs. 2.8 +/- 0.8; p = 0.5. Hepatotoxicity requiring discontinuation developed in 6 patients (17%). Seven (37%) IPAH and 8 SSD patients (47%) reached the composite end point (p = NS). Overall survival at 1 and 2 years was 100% and 100% vs 87% and 79% for IPAH and APAH-SSD patients, respectively (p = 0.075).
  
  
  CONCLUSIONS
  First-line bosentan monotherapy is associated with long-term improvement in functional class and good overall survival in patients with WHO class III IPAH. Most APAH-SSD patients experienced stability or decline in functional class and tended to have a higher mortality.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, Maryland, USA. rgirgis@jhmi.edu
authors.forename: Reda E
authors.initials: RE
authors.lastname: Girgis
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Mathai
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Krishnan
authors.forename: Fredrick M
authors.initials: FM
authors.lastname: Wigley
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hassoun
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077300:Bosentan; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function; D012595:Scleroderma, Systemic / Q000150:complications*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D000077300:Bosentan