Badesch David B, Hill Nicholas S, Burgess Gary, Rubin Lewis J, Barst Robyn J, Galiè Nazzareno, Simonneau Gerald
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
J Rheumatol. 2007 Dec;34(12):2417-22. Epub 2007 Nov 1.
Pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD) is difficult to manage, and has a poor prognosis. The phosphodiesterase-5 inhibitor sildenafil citrate enhances vasodilatation, has antiproliferative effects, and is effective in the treatment of PAH. We examined the efficacy and safety of oral sildenafil in patients with PAH-CTD.
In a 12-week, double-blind study (SUPER-1), 278 patients with PAH were randomized to oral placebo, sildenafil 20 mg, sildenafil 40 mg, or sildenafil 80 mg 3 times daily (tid). In a post-hoc subgroup analysis of 84 patients with PAH-CTD, exercise capacity, hemodynamic measures, World Health Organization functional class, and tolerability were assessed.
Forty-five percent of the patients had scleroderma, 23% had systemic lupus erythematosus, and the rest (32%) were categorized as other. Patients were predominantly functional class II (38%) or III (61%) at baseline. Sildenafil-treated patients exhibited mean increases in 6-minute walk distance at Week 12 of 42 m (95% CI 20, 64) for 20 mg, 36 m (95% CI 14, 58) for 40 mg, and 15 m (95% CI -24, 54) for 80 mg, while placebo-treated patients exhibited a mean decrease of 13 m (95% CI -36, 10). Improvement of at least 1 functional class occurred in 29%-42% of sildenafil-treated patients, compared to 5% for placebo. Significant improvements in mean pulmonary arterial pressure and pulmonary vascular resistance were observed with sildenafil 20 mg, and sildenafil was generally well tolerated.
In patients with PAH-CTD, sildenafil improves exercise capacity, hemodynamic measures (at the 20 mg dose), and functional class after 12 weeks of treatment.
与结缔组织病相关的肺动脉高压（PAH-CTD）难以治疗，预后较差。磷酸二酯酶-5抑制剂枸橼酸西地那非可增强血管舒张作用，具有抗增殖效果，对PAH治疗有效。我们研究了口服西地那非治疗PAH-CTD患者的疗效和安全性。
在一项为期12周的双盲研究（SUPER-1）中，278例PAH患者被随机分为口服安慰剂组、西地那非20mg组、西地那非40mg组或西地那非80mg组，每日3次（tid）。在对84例PAH-CTD患者进行的事后亚组分析中，评估了运动能力、血流动力学指标、世界卫生组织功能分级和耐受性。
45%的患者患有硬皮病，23%患有系统性红斑狼疮，其余（32%）归类为其他疾病。患者基线时主要为功能分级II级（38%）或III级（61%）。西地那非治疗的患者在第12周时6分钟步行距离平均增加，20mg组增加42m（95%CI 20，64），40mg组增加36m（95%CI 14，58），80mg组增加15m（95%CI -24，54），而安慰剂治疗的患者平均减少13m（95%CI -36，10）。29%-42%接受西地那非治疗的患者功能分级至少改善1级，而安慰剂组为5%。观察到西地那非20mg可使平均肺动脉压和肺血管阻力显著改善，且西地那非总体耐受性良好。
对于PAH-CTD患者，西地那非在治疗12周后可改善运动能力、血流动力学指标（20mg剂量时）和功能分级。
