Imatinib Mesylate as Add-on Therapy for Pulmonary Arterial Hypertension Results of the Randomized IMPRES Study
Imatinib Mesylate as Add-on Therapy for Pulmonary Arterial Hypertension Results of the Randomized IMPRES Study
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DOI：
10.1161/circulationaha.112.000765
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发表时间：
2013-03-12
期刊：
影响因子：
37.8
通讯作者：
Ghofrani, Hossein-Ardeschir
中科院分区：
文献类型：
--
作者：
Hoeper, Marius M.;Barst, Robyn J.;Ghofrani, Hossein-Ardeschir
背景：伊马替尼通过其对血小板衍生生长因子信号的抑制作用，可能有效治疗肺动脉高压（PAH）患者。方法与结果：伊马替尼治疗肺动脉高压，一项随机、疗效研究（IMPRES），一项随机、双盲、安慰剂对照的24周试验，评估了伊马替尼对肺血管阻力（>= 800 dynes）患者的疗效。cm（-5）对>= 2多环芳烃治疗有症状。主要结局是6分钟步行距离的改变。次要结局包括血流动力学、功能等级、血清n端脑利钠肽水平的变化以及到临床恶化的时间。核心研究完成后，患者可进入开放标签长期扩展研究。在纳入的202名患者中，41%的患者接受了3种PAH治疗，其余患者接受了2种治疗。24周后，经安慰剂校正的6分钟步行距离的平均治疗效果为32米（95%可信区间，12-52;P = 0.002），在继续使用伊马替尼的患者的扩展研究中保持了这一效果。肺血管阻力降低379达因。cm(-5)（95%置信区间，-502 ~ -255;P < 0.001，组间差异）。功能等级、临床恶化时间和死亡率在两种治疗之间没有差异。伊马替尼组的严重不良事件和停药比安慰剂组更频繁（分别为44%对30%和33%对18%）。接受伊马替尼和抗凝治疗的8例患者发生硬膜下血肿（核心研究2例，扩展研究6例）。结论：伊马替尼改善了晚期PAH患者的运动能力和血流动力学，但严重的不良事件和研究药物停药是常见的。需要进一步研究伊马替尼治疗PAH患者的长期安全性和有效性。临床试验注册-网址：http://www.clinicaltrials.gov。唯一标识符：NCT00902174（核心研究）；NCT01392495(扩展)。(循环。2013;127:1128 - 1138)。
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-Imatinib in Pulmonary Arterial Hypertension, a Randomized, Efficacy Study (IMPRES), a randomized, double-blind, placebo-controlled 24-week trial, evaluated imatinib in patients with pulmonary vascular resistance >= 800 dyne.s.cm(-5) symptomatic on >= 2 PAH therapies. The primary outcome was change in 6-minute walk distance. Secondary outcomes included changes in hemodynamics, functional class, serum levels of N-terminal brain natriuretic peptide, and time to clinical worsening. 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 6-minute walk distance was 32 m (95% confidence interval, 12-52; P = 0.002), an effect maintained in the extension study in patients remaining on imatinib. Pulmonary vascular resistance decreased by 379 dyne .s.cm(-5) (95% confidence interval, -502 to -255; P < 0.001, between-group difference). Functional class, time to clinical worsening, and mortality did not differ between treatments. Serious adverse events and discontinuations were more frequent with imatinib than placebo (44% versus 30% and 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. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00902174 (core study); NCT01392495 (extension). (Circulation. 2013;127:1128-1138.)