title: Clinical experience with bosentan and sitaxentan in connective tissue disease-associated pulmonary arterial hypertension.
abstract: OBJECTIVE
  To report outcomes in patients with CTD-pulmonary arterial hypertension (CTD-PAH) in an observational cohort treated with bosentan or sitaxentan and determine whether differences would justify a randomized, controlled multicentre study in this subpopulation.
  
  
  METHODS
  Patients with CTD-PAH, diagnosed by right-heart catheter studies, were assigned to either bosentan or sitaxentan based on physician choice. All patients were followed up with repeat assessments and data were collected for the local registry database.
  
  
  RESULTS
  The bosentan- (n = 32) and sitaxentan- (n = 22) treated groups had comparable haemodynamic and prognostic measures at baseline. Repeat haemodynamic assessments showed reductions in pulmonary vascular resistance with bosentan (-99 dynes/s/cm(5), P < 0.01) and sitaxentan (-92 dynes/s/cm(5), P < 0.05). The 6-min walk distance improved at 3 months with sitaxentan (25 m, P < 0.05). N-terminal pro-B-type natriuretic peptide levels fell in the bosentan cohort at 6 months (-70 pmol/l, P < 0.05) and 1 year (-83 pmol/l, P < 0.01). Haemoglobin fell with both drugs (at 3 months -0.5 g/dl bosentan, P < 0.05 and -0.9 g/dl sitaxentan, P < 0.005). Calculations of the difference in treatment effect did not demonstrate superiority of either therapy. The 1-year estimated clinical worsening event rates were high: 41% sitaxentan, 62% bosentan (P = 0.142), with serious event rates of 27 and 14% (P = 0.263, log-rank test), respectively. Six patients discontinued bosentan because of transaminase elevation within the first year. Estimated 1-year survival was similar in both groups and 96% overall.
  
  
  CONCLUSIONS
  Both sitaxentan and bosentan appear effective in CTD-PAH, but the apparent additional benefit of sitaxentan reported from the open-label Sitaxentan To Relieve ImpaireD Exercise-2X study was not confirmed in this observational cohort. Although survival has improved, event rates continue to be substantial and CTD-PAH remains a therapeutic challenge.
authors.affiliation: The National Pulmonary Hypertension Unit, Royal Free Hospital, London, UK. cjvalerio@doctors.net.uk
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Valerio
authors.forename: Clive E
authors.initials: CE
authors.lastname: Handler
authors.forename: Peter
authors.initials: P
authors.lastname: Kabunga
authors.forename: Colette J
authors.initials: CJ
authors.lastname: Smith
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Denton
authors.forename: John G
authors.initials: JG
authors.lastname: Coghlan
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000077300:Bosentan; D002986:Clinical Trials as Topic; D003240:Connective Tissue Diseases / Q000150:complications*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013223:Statistics as Topic; D013449:Sulfonamides / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D007555:Isoxazoles; D013449:Sulfonamides; D013876:Thiophenes; C106276:sitaxsentan; D000077300:Bosentan