Vascular endothelial growth factor in ischemia for vascular angiogenesis
Vascular endothelial growth factor in ischemia for vascular angiogenesis
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DOI：
10.1161/01.cir.0000061911.47710.8a
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发表时间：
2003-03-18
期刊：
影响因子：
37.8
通讯作者：
McCluskey, ER
中科院分区：
文献类型：
--
作者：
Henry, TD;Annex, BH;McCluskey, ER
背景：重组人血管内皮生长因子蛋白（rhVEGF）在动物模型中刺激血管生成，并且在I期临床试验中耐受性良好。VIVA （Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis）是一项双盲、安慰剂对照试验，旨在评估冠状动脉内和静脉输注rhVEGF的安全性和有效性。方法与结果：178例不适合标准血运重建术的稳定的劳损性心绞痛患者随机分为安慰剂组、低剂量rhVEGF组（17 ng）。公斤(1)。min(-1))或高剂量rhVEGF (50 ng。公斤(1)。Min(-1))第0天冠状动脉内输注，第3、6、9天静脉输注。在基线、第60天和第120天分别进行运动跑步机试验、心绞痛分级和生活质量评估。在基线和第60天进行心肌灌注成像。在第60天，运动跑步机试验（ETT）时间从基线的变化在两组之间没有差异（安慰剂，+48秒；低剂量，+30秒；高剂量，+30秒）。各组心绞痛分级及生活质量均有显著改善，组间无差异。到第120天，安慰剂治疗的患者在所有三项指标中均显示获益降低，与低剂量rhVEGF相比无显著差异。相比之下，与安慰剂相比，高剂量rhVEGF在心绞痛类别上有显著改善（P=0.05），在ETT时间（P=0.15）和心绞痛频率（P=0.09）上无显著变化。结论- rhvegf是安全且耐受性良好的。在第60天的所有测量中，rhVEGF与安慰剂相比没有改善。到第120天，高剂量rhVEGF显著改善心绞痛，ETT时间和心绞痛频率均有良好趋势。
Background-Recombinant human vascular endothelial growth factor protein (rhVEGF) stimulates angiogenesis in animal models and was well tolerated in Phase I clinical trials. VIVA (Vascular endothelial growth factor in Ischemia for Vascular Angiogenesis) is a double-blind, placebo-controlled trial designed to evaluate the safety and efficacy of intracoronary and intravenous infusions of rhVEGF.Methods and Results-A total of 178 patients with stable exertional angina, unsuitable for standard revascularization, were randomized to receive placebo, low-dose rhVEGF (17 ng . kg(-1) . min(-1)), or high-dose rhVEGF (50 ng . kg(-1) . min(-1)) by intracoronary infusion on day 0, followed by intravenous infusions on days 3, 6, and 9. Exercise treadmill tests, angina class, and quality of life assessments were performed at baseline, day 60, and day 120. Myocardial perfusion imaging was performed at baseline and day 60. At day 60, the change in exercise treadmill test (ETT) time from baseline was not different between groups (placebo, +48 seconds; low dose, +30 seconds; high dose, +30 seconds). Angina class and quality of life were significantly improved within each group, with no difference between groups. By day 120, placebo-treated patients demonstrated reduced benefit in all three measures, with no significant difference compared with low-dose rhVEGF. In contrast, high-dose rhVEGF resulted in significant improvement in angina class (P=0.05) and nonsignificant trends in ETT time (P=0.15) and angina frequency (P=0.09) as compared with placebo.Conclusions-rhVEGF seems to be safe and well tolerated. rhVEGF offered no improvement beyond placebo in all measurements by day 60. By day 120, high-dose rhVEGF resulted in significant improvement in angina and favorable trends in ETT time and angina frequency.