Circulation：曲罗尼尔有望成为肺动脉高压一线治疗药物

　　中国学者的一项研究表明，在未接受其他治疗的肺动脉高压（PAH）患者中，口服曲罗尼尔（treprostinil）可改善运动能力，并有望成为一线治疗可选方案。论文于2013年1月10日在线发表于《循环》（Circulation）。

　　此项研究共纳入349例未接受内皮素受体拮抗剂和磷酸二酯酶5型抑制剂治疗的PAH患者，并随机分配给予曲罗尼尔（233例）或安慰剂（116例）治疗。主要终点为12周时6分钟步行距离（6MWD）至基线变化。次要终点为Borg呼吸困难指数、临床恶化和PAH症状。

　　结果显示，12周时6MWD的治疗效果为23.0米。在研药物血清峰浓度（26.0米；P=0.0001）和谷浓度（17.0米；P=0.0025）时均可观察到6MWD改善。除6MWD/Borg呼吸困难指数联合指标出现改善之外，其他次要终点均无显著变化。口服曲罗尼尔耐受性良好；最常见的副作用为头痛、恶心、腹泻和下颚痛。

Efficacy and Safety of Oral Treprostinil Monotherapy for the Treatment of Pulmonary Arterial Hypertension: A Randomized Controlled Trial

Background—Pulmonary arterial hypertension (PAH) is a progressive, fatal disease with no cure. Parenteral and inhaled prostacyclin analogue therapies are effective for the treatment of PAH but complicated administration requirements can limit the use of these therapies in patients with less severe disease. This study was designed to evaluate the safety and efficacy of the oral prostacyclin analogue, treprostinil diolamine, as initial treatment for de novo PAH.

Methods and Results—Three hundred and forty-nine patients (intent-to-treat population [ITT]) not receiving endothelin receptor antagonist or phosphodiesterase type-5 inhibitor background therapy were randomized (treprostinil, n=233; placebo, n=116). The primary analysis population (modified ITT [mITT]) included 228 patients (treprostinil, n=151; placebo, n=77) with access to 0.25 mg treprostinil tablets at randomization. The primary endpoint was change from baseline in 6-minute walk distance (6MWD) at week 12. Secondary endpoints included Borg dyspnea index, clinical worsening, and symptoms of PAH. The week 12 treatment effect for 6MWD (mITT population) was 23.0 m (p=0.0125). For the ITT population, 6MWD improvements were observed at peak (26.0 m; p=0.0001) and trough plasma study drug concentrations (17.0 m; p=0.0025). Other than an improvement in the combined 6MWD/Borg dyspnea score, there were no significant changes in secondary endpoints. Oral treprostinil therapy was generally well-tolerated; most common adverse events (ITT) were headache (69%), nausea (39%), diarrhea (37%), and pain in jaw (25%).

Conclusions—Oral treprostinil improves exercise capacity in PAH patients not receiving other treatment. Oral treprostinil could provide a convenient, first-line prostacyclin treatment option for PAH patients not requiring more intensive therapy.