Sildenafil citrate therapy for pulmonary arterial hypertension
Sildenafil citrate therapy for pulmonary arterial hypertension
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DOI：
10.1056/nejmoa050010
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发表时间：
2005-11-17
影响因子：
158.5
通讯作者：
Simonneau, G
中科院分区：
文献类型：
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作者：
Galiè, N;Ghofrani, HA;Simonneau, G
背景西地那非抑制磷酸二酯酶5，一种代谢环鸟苷一磷酸的酶，从而加强环鸟苷一磷酸介导的血管平滑肌细胞的松弛和生长抑制，包括肺中的血管平滑肌细胞。方法在这项双盲、安慰剂对照研究中，我们随机将278名有症状的肺动脉高压(特发性或伴发结缔组织病或先天性体肺分流)患者随机分配到安慰剂或西地那非(20、40或80 mg)，每天三次，持续12周。主要终点是6分钟步行距离从基线到第12周的变化。平均肺动脉压和世界卫生组织(WHO)功能分级的变化以及临床恶化的发生率也被评估，但这项研究并不能评估死亡率。结果所有西地那非组的6分钟步行距离较基线增加，20、40和80 mg西地那非的平均安慰剂校正治疗效果分别为45m(+13.0%)、46m(+13.3%)和50m(+14.7%)(P
BackgroundSildenafil inhibits phosphodiesterase type 5, an enzyme that metabolizes cyclic guanosine monophosphate, thereby enhancing the cyclic guanosine monophosphate-mediated relaxation and growth inhibition of vascular smooth-muscle cells, including those in the lung.MethodsIn this double-blind, placebo-controlled study, we randomly assigned 278 patients with symptomatic pulmonary arterial hypertension (either idiopathic or associated with connective-tissue disease or with repaired congenital systemic-to-pulmonary shunts) to placebo or sildenafil (20, 40, or 80 mg) orally three times daily for 12 weeks. The primary end point was the change from baseline to week 12 in the distance walked in six minutes. The change in mean pulmonary-artery pressure and World Health Organization (WHO) functional class and the incidence of clinical worsening were also assessed, but the study was not powered to assess mortality. Patients completing the 12-week randomized study could enter a long-term extension study.ResultsThe distance walked in six minutes increased from baseline in all sildenafil groups; the mean placebo-corrected treatment effects were 45 m (+13.0 percent), 46 m (+13.3 percent), and 50 m (+14.7 percent) for 20, 40, and 80 mg of sildenafil, respectively (P