Circulation：伊马替尼治疗肺动脉高压风险获益并存

　　欧美学者的一项研究表明，在晚期肺动脉高血压患者中，伊马替尼可改善运动能力和血流动力学指标，但严重不良事件和停药情况较为常见。论文于2013年2月12日在线发表于《循环》（Circulation）。

　　此项随机、双盲、安慰剂对照试验共纳入202例肺动脉高压患者。受试者肺血管阻力（PVR）≥800 dynes•sec•cm^-5，并且在接受2种以上治疗时仍具有症状性表现。主要转归为6分钟步行距离（6MWD）变化。次要转归包括血流动力学、功能分级、血清N-末端脑利钠肽（NT-proBNP）以及至临床恶化时间（TTCW）变化。核心研究结束后，患者可进入开放标签的长期扩展研究。

　　结果显示，24周后6MWD的平均安慰剂校正治疗效果为32m（P=0.002），并且上述疗效在扩展研究仍接受伊马替尼治疗的患者中可继续维持。PVR降低379 dynes•sec•cm^-5（P<0.001）。两组患者在功能分级、TTCW和死亡率方面无显著差异。伊马替尼组的严重不良事件和停药率均高于安慰剂组。8例接受伊马替尼和抗凝治疗的患者出现硬膜下血肿（2例为核心研究，6例为扩展研究）。

Imatinib Mesylate as Add-On Therapy for Pulmonary Arterial Hypertension: Results of the Randomized IMPRES Study

Background—By its inhibitory effect on platelet-derived growth factor signaling, imatinib could be efficacious in treating patients with pulmonary arterial hypertension (PAH).

Methods and Results—IMPRES, a randomized, double-blind, placebo-controlled 24-week trial evaluated imatinib in patients with pulmonary vascular resistance (PVR) ≥800 dynes•sec•cm^-5 symptomatic on ≥2 PAH therapies. The primary outcome was change in 6-minute walk distance (6MWD). Secondary outcomes included changes in hemodynamics, functional class, serum levels of N-terminal brain natriuretic peptide (NT-proBNP), and time to clinical worsening (TTCW). After completion of the core study, patients could enter an open-label long-term extension study. Of 202 patients enrolled, 41% patients received 3 PAH therapies with the remainder on 2 therapies. After 24 weeks, the mean placebo-corrected treatment-effect on 6MWD was 32 m (95% confidence interval [CI], 12, 52;P=0.002), an effect maintained in the extension study in patients remaining on imatinib. PVR decreased by 379 dynes•sec•cm^-5 (95% CI: -502, -255; P<0.001; between-group difference). Functional class, TTCW and mortality did not differ between treatments. Serious adverse events and discontinuations were more frequent with imatinib than placebo (44% versus 30%, 33% versus 18% respectively). Subdural hematoma occurred in 8 patients (2 in the core study, 6 in the extension) receiving imatinib and anticoagulation.

Conclusions—Imatinib improved exercise capacity and hemodynamics in patients with advanced PAH but serious adverse events and study drug discontinuations were common. Further studies are needed to investigate the long-term safety and efficacy of imatinib in patients with PAH.