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

Rheumatology (Oxford). 2010 Mar;49(3):490-500. doi: 10.1093/rheumatology/kep398. Epub 2009 Dec 16.

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.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Bosentan
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Endothelin A Receptor Antagonists
  • Epidemiologic Methods
  • Epoprostenol / therapeutic use
  • Exercise Test / methods
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / etiology
  • Hypertension, Pulmonary / physiopathology
  • Iloprost / therapeutic use
  • Male
  • Middle Aged
  • Piperazines / therapeutic use
  • Purines / therapeutic use
  • Scleroderma, Systemic / complications*
  • Scleroderma, Systemic / physiopathology
  • Sildenafil Citrate
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Sulfones / therapeutic use
  • Treatment Outcome

Substances

  • Antihypertensive Agents
  • Endothelin A Receptor Antagonists
  • Piperazines
  • Purines
  • Sulfonamides
  • Sulfones
  • Sildenafil Citrate
  • Epoprostenol
  • Iloprost
  • Bosentan