Clinical experience with bosentan and sitaxentan in connective tissue disease-associated pulmonary arterial hypertension
Rheumatology, 08/05/2010
Valerio CJ et al. – The objective was 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. 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.
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 collected for local registry database
- 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/cm5, P < 0.01) and sitaxentan (–92 dynes/s/cm5, P < 0.05)
- 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 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 difference in treatment effect did not demonstrate superiority of either therapy
- 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)
- 6 patients discontinued bosentan because of transaminase elevation within first year
- Estimated 1-year survival was similar in both groups and 96% overall
