Tadalafil Therapy for Pulmonary Arterial Hypertension
Tadalafil Therapy for Pulmonary Arterial Hypertension
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DOI：
10.1161/circulationaha.108.839274
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发表时间：
2009-06-09
期刊：
影响因子：
37.8
通讯作者：
Barst, Robyn J.
中科院分区：
文献类型：
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作者：
Galie, Nazzareno;Brundage, Bruce H.;Barst, Robyn J.
背景：肺动脉高压的治疗选择针对前列环素、内皮素或一氧化氮途径。他达拉非是一种磷酸二酯酶5型抑制剂，可增加一氧化氮途径的最终介质cGMP。方法和结果：在这项为期16周的双盲安慰剂对照研究中，405例肺动脉高压（特发性或相关）患者，无论是未经治疗还是接受内皮素受体拮抗剂波生坦的背景治疗，随机分为安慰剂组或他达拉非2.5、10、20或40 mg，每日口服一次。主要终点是6分钟内步行距离从基线到第16周的变化。还评估了世界卫生组织功能等级、临床恶化和健康相关生活质量的变化。完成16周研究的患者可以进入长期扩展研究。他达拉非可增加6分钟步行距离，且呈剂量依赖性；只有40mg剂量达到预定水平的统计学意义(P
Background-Treatment options for pulmonary arterial hypertension target the prostacyclin, endothelin, or nitric oxide pathways. Tadalafil, a phosphodiesterase type-5 inhibitor, increases cGMP, the final mediator in the nitric oxide pathway.Methods and Results-In this 16-week, double-blind, placebo-controlled study, 405 patients with pulmonary arterial hypertension (idiopathic or associated), either treatment-naive or on background therapy with the endothelin receptor antagonist bosentan, were randomized to placebo or tadalafil 2.5, 10, 20, or 40 mg orally once daily. The primary end point was the change from baseline to week 16 in the distance walked in 6 minutes. Changes in World Health Organization functional class, clinical worsening, and health-related quality of life were also assessed. Patients completing the 16-week study could enter a long-term extension study. Tadalafil increased the distance walked in 6 minutes in a dose-dependent manner; only the 40-mg dose met the prespecified level of statistical significance (P