Bosentan (BOS) is an oral endothelin A&B receptor antagonist effective for PAH treatment. Patients (Pts.) with initial benefit can deteriorate or develop liver function test abnormalities (LFab) requiring drug cessation. Sitaxsentan (SITAX) is a selective oral endothelin A receptor antagonist in clinical trials. Between 10/01/03 and 1/23/04 13 pts. enrolled at this center in an open-label safety study of SITAX. 11 pts. were previously treated with BOS which was discontinued due to LFab (3) or deteriorating functional capacity and walk test (6MW)(8). We present their short term response to SITAX.
Pts with LFab on BOS (L1-L3)remained off BOS prior to SITAX intiation until LFab normalized. In pts. transitioned due to clinical deterioration (1-7), baseline values were on BOS. 10 pts. have been followed for 12 weeks with 6MW, exam and WHO. The change in 6MW was compared to baseline values using two-sided paired t-test.
The mean improvement (± SE) in 6MW with SITAX was 36.5 ± 10.56m (p=0.0072). No Pts. with LFab on BOS experienced signficant LFab with SITAX. One pt. (not included due to no efficacy measurements)who refused epoprostenol for clinical deterioration transitioned to SITAX from BOS. This pt. worsened at wk 5 started epoprostenol and subsequently died.
SITAX appears to offer potential as oral therapy for pts. with PAH who fail BOS due to LFab or clinical deterioration.
Failure or complications with one endothelin receptor antagonist does not presuppose failure with another. Different endothelin receptor antagonists may offer unique advantages. Pt.BaselineBaseline12 wk12 wkChangeWHO6MWTWHO6MWT6MWTL133592408+49L232753372+97L325792600+21133903432+422329432940324702477+7433303390+60523202342+22634663461−6733873459+72
A.E. Frost, Encysive,Actelion