title: Long-term outcome of systemic sclerosis-associated pulmonary arterial hypertension treated with bosentan as first-line monotherapy followed or not by the addition of prostanoids or sildenafil.
abstract: OBJECTIVE
  Data on long-term efficacy of bosentan, an oral dual ET receptor antagonist, in SSc-associated pulmonary arterial hypertension (SSc-PAH) are lacking. We aimed to describe the long-term outcome of SSc-PAH treated with first-line monotherapy bosentan followed or not by the addition of prostanoids or sildenafil.
  
  
  METHODS
  A prospective analysis of 49 consecutive SSc-PAH patients treated with first-line bosentan was performed. New York Heart Association (NYHA) functional class, 6-min walk distance (6MWD) and haemodynamics were assessed at baseline and after 4 and 12 months.
  
  
  RESULTS
  At 4 months, significant improvements in NYHA functional class and haemodynamics were observed with stabilization at 1 year. There was no significant improvement in 6MWD. Overall survival estimates were 80, 56 and 51% at 1, 2 and 3 years, respectively, and were significantly worse than those in a cohort of patients with idiopathic PAH (92, 89 and 79% at 1, 2 and 3 years, respectively; P < 0.0001). Twenty-three patients (47%) died after a mean follow-up of 23 (18) months. In multivariate analysis, baseline and 4-month NYHA functional class and 4-month cardiac index were independent factors associated with overall survival.
  
  
  CONCLUSIONS
  In our cohort of consecutive SSc-PAH patients treated with first-line bosentan, improvement in NYHA functional class and haemodynamics was significant after 4 months of treatment and stabilized afterwards. One-year overall survival rate was higher than previously reported in historical series. However, long-term prognosis remains poor. Our study underlines the importance of haemodynamic evaluation 4 months after the start of treatment to provide strong parameters associated with survival-like cardiac index.
authors.affiliation: Universite Paris-Sud, Faculte de Medecine, Kremlin-Bice tre, France.
authors.forename: David
authors.initials: D
authors.lastname: Launay
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.forename: Jérôme
authors.initials: J
authors.lastname: Le Pavec
authors.forename: Laurent
authors.initials: L
authors.lastname: Savale
authors.forename: Colas
authors.initials: C
authors.lastname: Tchérakian
authors.forename: Azzedine
authors.initials: A
authors.lastname: Yaïci
authors.forename: Lara
authors.initials: L
authors.lastname: Achouh
authors.forename: Florence
authors.initials: F
authors.lastname: Parent
authors.forename: Xavier
authors.initials: X
authors.lastname: Jais
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000077300:Bosentan; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D065130:Endothelin A Receptor Antagonists; D004812:Epidemiologic Methods; D011464:Epoprostenol / Q000627:therapeutic use; D005080:Exercise Test / Q000379:methods; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D016285:Iloprost / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000627:therapeutic use; D011687:Purines / Q000627:therapeutic use; D012595:Scleroderma, Systemic / Q000150:complications* / Q000503:physiopathology; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013450:Sulfones / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D013450:Sulfones; D000068677:Sildenafil Citrate; D011464:Epoprostenol; D016285:Iloprost; D000077300:Bosentan