title: Sitaxsentan for the treatment of pulmonary arterial hypertension: a 1-year, prospective, open-label observation of outcome and survival.
abstract: BACKGROUND
  Despite advances in the management of pulmonary arterial hypertension (PAH), the mortality rate remains excessive. Long-term efficacy evaluations are needed to guide therapeutic management. The purpose of this study is to present 1-year observational data with two endothelin antagonists, sitaxsentan and bosentan, in a prospective, open-label study.
  
  
  METHODS
  The present study was a prospective, international, multicenter, randomized, open-label extension of the Sitaxsentan To Relieve Impaired Exercise-2 trial. All-cause mortality, time to discontinuation (all causes) from monotherapy, time to discontinuation due to adverse events, time to elevations in and time to discontinuation due to elevated hepatic transaminases, and time to first clinical worsening event were evaluated. Patients initially receiving sitaxsentan at 50 mg were excluded from the main analysis. The distributions of time-to-event variables are estimated using Kaplan-Meier methods, and treatment effects are evaluated using the Cox proportional hazards model.
  
  
  RESULTS
  Patients treated with sitaxsentan at 100 mg had 96% overall survival and a 34% risk for a clinical worsening event by 1 year. In addition, there was a 6% risk of elevated aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels > 3 x upper limit of normal range (ULN) at 1 year and a 15% risk of discontinuation due to adverse events. Patients treated with bosentan had 88% overall survival and a 40% risk of a clinical worsening event by 1 year. In addition, there was a 14% risk for elevated AST and/or ALT levels > 3 x ULN at 1 year and a 30% risk of discontinuation due to adverse events.
  
  
  CONCLUSIONS
  At 1 year, sitaxsentan therapy appears safe and efficacious for patients with PAH; reductions in mortality and the risk for clinical worsening events provide support for durability of efficacy.
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL. Electronic address: rbenza@wpahs.org.
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Benza
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, NY.
authors.forename: Robyn J
authors.initials: RJ
authors.lastname: Barst
authors.affiliation: Cardiology Institute, University of Bologna, Bologna, Italy.
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galie
authors.affiliation: Baylor College of Medicine, Houston, TX.
authors.forename: Adaani
authors.initials: A
authors.lastname: Frost
authors.affiliation: Johns Hopkins University, School of Medicine, Baltimore, MD.
authors.forename: Reda E
authors.initials: RE
authors.lastname: Girgis
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, SC.
authors.forename: Kristin B
authors.initials: KB
authors.lastname: Highland
authors.affiliation: Department of Medicine, Medical University of South Carolina, Charleston, SC.
authors.forename: Charlie
authors.initials: C
authors.lastname: Strange
authors.affiliation: Royal College of Physicians of London, London, UK.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Black
authors.affiliation: University of Colorado Health Sciences Center, Denver, CO.
authors.forename: David B
authors.initials: DB
authors.lastname: Badesch
authors.affiliation: University of California, San Diego Medical Center, La Jolla, CA.
authors.forename: Lewis
authors.initials: L
authors.lastname: Rubin
authors.affiliation: University of Washington, Seattle, WA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fleming
authors.affiliation: Erasmus University Brussels, Brussels, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Naeije
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D065128:Endothelin Receptor Antagonists; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000401:mortality; D007555:Isoxazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate; D013876:Thiophenes / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D065128:Endothelin Receptor Antagonists; D007555:Isoxazoles; D013876:Thiophenes; C106276:sitaxsentan