{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T22:32:32Z","timestamp":1774564352279,"version":"3.50.1"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2004,2,1]],"date-time":"2004-02-01T00:00:00Z","timestamp":1075593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Sitaxsentan may benefit patients with pulmonary arterial hypertension by blocking the vasoconstrictor effects of endothelin-A while maintaining the vasodilator\/clearance functions of endothelin-B receptors. Patients with pulmonary arterial hypertension that was idiopathic, related to connective tissue disease or congenital heart disease, were randomized to receive placebo (n = 60), sitaxsentan 100 mg (n = 55), or sitaxsentan 300 mg (n = 63) orally once daily for 12 weeks. The primary endpoint was change in peak V\u0307O2 at Week 12. Secondary endpoints included 6-minute walk, New York Heart Association class, V\u0307O2 at anaerobic threshold, V\u0307E per carbon dioxide production at anaerobic threshold, hemodynamics, quality of life, and time to clinical worsening. Although the 300-mg group increased peak V\u0307O2 compared with placebo (+3.1%, p &amp;lt; 0.01), none of the other endpoints derived from cardiopulmonary exercise testing were met. However, both the 100-mg dose and the 300-mg dose, compared with placebo, increased 6-minute walk distance (100 mg: +35 m, p &amp;lt; 0.01; 300 mg: +33 m, p &amp;lt; 0.01); functional class, cardiac index, and pulmonary vascular resistance also improved (p &amp;lt; 0.02 for each parameter at both doses). The incidence of elevated aminotransferase values (&amp;gt; three times normal) was 3% for the placebo group, 0% for the 100-mg group, and 10% for the 300-mg group.<\/jats:p>","DOI":"10.1164\/rccm.200307-957oc","type":"journal-article","created":{"date-parts":[[2003,11,24]],"date-time":"2003-11-24T20:23:19Z","timestamp":1069705399000},"page":"441-447","source":"Crossref","is-referenced-by-count":547,"title":["Sitaxsentan Therapy for Pulmonary Arterial Hypertension"],"prefix":"10.1093","volume":"169","author":[{"given":"Robyn J.","family":"Barst","sequence":"first","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"David","family":"Langleben","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Adaani","family":"Frost","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Evelyn M.","family":"Horn","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Ronald","family":"Oudiz","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Shelley","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Vallerie","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Nicholas","family":"Hill","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Victor F.","family":"Tapson","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Ivan M.","family":"Robbins","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Diane","family":"Zwicke","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Benjamin","family":"Duncan","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Richard A. F.","family":"Dixon","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. Davis Jewish General Hospital, Montreal, Canada; Harbor-University of California at Los Angeles Medical Center, Torrance; University of Southern California, Los Angeles, California; Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois; Rhode Island Hospital, Providence, Rhode Island; Duke University Medical Center, Durham, North Carolina; Vanderbilt University Hospital, Nashville, Tennessee; University of Wisconsin Medical Center, Milwaukee, Wisconsin; ICOS Corporation, Bothell, Washington; Baylor College of Medicine; and Encysive Pharmaceuticals, Houston, Texas"}]},{"given":"Lyn R.","family":"Frumkin","sequence":"additional","affiliation":[{"name":"Columbia University College of Physicians & Surgeons, New York, New York; Sir Mortimer B. 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