选择性内皮素-A受体拮抗剂sitaxsentan治疗肺动脉高压  

Treatment of Pulmonary Arterial Hypertension With the Selective Endothelin-A Receptor Antagonist Sitaxsentan

作　　者：Barst R.J. Langleben D. Badesch D. 郭俊 

机构地区：[1]Department of Pediatrics, Columbia University Medical Center, New York, NY, United States Dr.

出　　处：《世界核心医学期刊文摘（心脏病学分册）》2006年第7期47-48,共2页

摘　　要：Objectives: We sought to determine the optimal dose of the selective endothelin A(ETA) receptor antagonist sitaxsentan for the treatment of pulmonary arterial hypertension(PAH); for observation only, an open-label(OL) bosentan arm was included. Background: Endothelin is a mediator of PAH. In a preliminary PAH study, the selective ETA receptor antagonist sitaxsentan improved six-min walk(6MW) distance,World Health Organization(WHO) functional class(FC), and hemodynamics. Methods: In this double-blind, placebo-controlled 18-week study, 247 PAH patients(idiopathic, or associated with connective tissue disease or congenital heart disease) were randomized; 245 patients were treated: placebo(n=62), sitaxsentan 50 mg(n=62) or 100 mg(n=61), or OL(6MW tests, Borg dyspnea scores, and WHO FC assessments third-party blind) bosentan(n=60). The primary end point was change in 6MW distance from baseline to week 18. Secondary end points included change in WHO FC, time to clinical worsening, and change in Borg dyspnea score. Results: At week 18, patients treated with sitaxsentan 100 mg had an increased 6MW distance compared with the placebo group(31.4 m, p=0.03), and an improved WHO FC(p=0.04). The placebo-subtracted treatment effect for sitaxsentan 50 mg was 24.2 m(p=0.07) and for OL bosentan, 29.5 m(p=0.05). The incidence of elevated hepatic transaminases( >3×the upper limit of normal) was 6%for placebo, 5%for sitaxsentan 50 mg, 3%for sitaxsentan 100 mg, and 11%for bosentan. Conclusions: Treatment with the selective ETA receptor antagonist sitaxsentan, orally once daily at a dose of 100 mg, improves exercise capacity and WHO FC in PAH patients, with a low incidence of hepatic toxicity.Objectives: We sought to determine the optimal dose of the selective endothelin A(ETA) receptor antagonist sitaxsentan for the treatment of pulmonary arterial hypertension(PAH); for observation only, an open-label(OL) bosentan arm was included. Background: Endothelin is a mediator of PAH. In a preliminary PAH study, the selective ETA receptor antagonist sitaxsentan improved six-min walk(6MW) distance,World Health Organization(WHO) functional class(FC), and hemodynamics. Methods: In this double-blind, placebo-controlled 18-week study, 247 PAH patients(idiopathic, or associated with connective tissue disease or congenital heart disease) were randomized; 245 patients were treated: placebo(n=62), sitaxsentan 50 mg(n=62) or 100 mg(n=61), or OL(6MW tests, Borg dyspnea scores, and WHO FC assessments third-party blind) bosentan(n=60). The primary end point was change in 6MW distance from baseline to week 18. Secondary end points included change in WHO FC, time to clinical worsening, and change in Borg dyspnea score. Results: At week 18, patients treated with sitaxsentan 100 mg had an increased 6MW distance compared with the placebo group(31.4 m, p=0.03), and an improved WHO FC(p=0.04). The placebo-subtracted treatment effect for sitaxsentan 50 mg was 24.2 m(p=0.07) and for OL bosentan, 29.5 m(p=0.05). The incidence of elevated hepatic transaminases( >3×the upper limit of normal) was 6%for placebo, 5%for sitaxsentan 50 mg, 3%for sitaxsentan 100 mg, and 11%for bosentan. Conclusions: Treatment with the selective ETA receptor antagonist sitaxsentan, orally once daily at a dose of 100 mg, improves exercise capacity and WHO FC in PAH patients, with a low incidence of hepatic toxicity.

关 键 词：肺动脉高压 SITAXSENTAN 受体拮抗剂 内皮素 波生坦 最佳剂量 呼吸困难评分 结缔组织病 

分 类 号：R543.2[医药卫生—心血管疾病]