PMID- 17234519
OWN - NLM
STAT- MEDLINE
DCOM- 20070201
LR  - 20181201
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 26
IP  - 1
DP  - 2007 Jan
TI  - Sitaxsentan treatment for patients with pulmonary arterial hypertension 
      discontinuing bosentan.
PG  - 63-9
AB  - BACKGROUND: Bosentan, an oral ET(A)/ET(B) receptor antagonist, is approved for 
      the treatment of pulmonary arterial hypertension (PAH). However, some patients 
      discontinue bosentan because of hepatotoxicity or inadequate efficacy. 
      Sitaxsentan, an oral, ET(A)-selective endothelin antagonist currently under 
      investigation, may be an alternative treatment option. In this study we evaluate 
      the safety and efficacy of sitaxsentan in patients discontinuing bosentan. 
      METHODS: Forty-eight patients with idiopathic PAH or PAH associated with 
      connective-tissue disease or congenital heart disease were randomized 
      (double-blind) to a single daily dose of either 50 mg or 100 mg sitaxsentan. 
      Thirty-five of the 48 patients discontinued bosentan because of inadequate 
      efficacy, as judged by the investigator, and 13 discontinued bosentan for safety 
      concerns. Study end-points included change in 6-minute walk distance (6MWD), 
      change in World Health Organization (WHO) functional class, time to clinical 
      worsening, and change in Borg dyspnea score (Borg) from baseline to Week 12. 
      RESULTS: With 100 mg sitaxsentan, 5 of 15 patients (33%) who discontinued 
      bosentan because inadequate efficacy improved, demonstrating a >15% increase in 
      6MWD, vs 2 of 20 patients (10%) treated with 50 mg sitaxsentan. Fifteen percent 
      and 20% of these patients had a >15% decrease in 6MWD in the 50- and 100-mg 
      groups, respectively. Similar results were seen for the Borg and WHO functional 
      class. Of the 12 patients discontinuing bosentan because of hepatotoxicity, 1 
      developed elevated liver enzymes at 13 weeks of sitaxsentan therapy. Overall, 
      sitaxsentan was well tolerated. CONCLUSIONS: Sitaxsentan may represent a safe and 
      efficacious alternative endothelin receptor antagonist for patients discontinuing 
      bosentan.
FAU - Benza, Raymond L
AU  - Benza RL
AD  - Division of Cardiology, University of Alabama at Birmingham, Birmingham, Alabama 
      35294-0006, USA. rbenza@uab.edu
FAU - Mehta, Sanjay
AU  - Mehta S
FAU - Keogh, Anne
AU  - Keogh A
FAU - Lawrence, E Clinton
AU  - Lawrence EC
FAU - Oudiz, Ronald J
AU  - Oudiz RJ
FAU - Barst, Robyn J
AU  - Barst RJ
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Isoxazoles)
RN  - 0 (Sulfonamides)
RN  - 0 (Thiophenes)
RN  - J9QH779MEM (sitaxsentan)
RN  - Q326023R30 (Bosentan)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Antihypertensive Agents/*therapeutic use
MH  - Bosentan
MH  - Child
MH  - Double-Blind Method
MH  - *Endothelin Receptor Antagonists
MH  - Female
MH  - Follow-Up Studies
MH  - Humans
MH  - Hypertension, Pulmonary/*drug therapy
MH  - Isoxazoles/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Sulfonamides/*therapeutic use
MH  - Thiophenes/*therapeutic use
MH  - Treatment Outcome
EDAT- 2007/01/20 09:00
MHDA- 2007/02/03 09:00
CRDT- 2007/01/20 09:00
PHST- 2006/01/20 00:00 [received]
PHST- 2006/08/07 00:00 [revised]
PHST- 2006/10/29 00:00 [accepted]
PHST- 2007/01/20 09:00 [pubmed]
PHST- 2007/02/03 09:00 [medline]
PHST- 2007/01/20 09:00 [entrez]
AID - S1053-2498(06)00774-1 [pii]
AID - 10.1016/j.healun.2006.10.019 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2007 Jan;26(1):63-9. doi: 10.1016/j.healun.2006.10.019.