Local perivascular delivery of basic fibroblast growth factor in patients undergoing coronary bypass surgery - Results of a phase I randomized, double-blind, placebo-controlled trial
Local perivascular delivery of basic fibroblast growth factor in patients undergoing coronary bypass surgery - Results of a phase I randomized, double-blind, placebo-controlled trial
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DOI：
10.1161/01.cir.100.18.1865
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发表时间：
1999-11-02
期刊：
影响因子：
37.8
通讯作者：
Simons, M
中科院分区：
文献类型：
--
作者：
Laham, RJ;Sellke, FW;Simons, M
背景--血管新生是一种很有前途的治疗策略，适用于那些不适合标准血运重建的患者，因为它能促进缺血心肌中新血管的生长。方法和结果--我们进行了一项随机、双盲、安慰剂对照的碱性成纤维细胞生长因子研究（bFGF; 10或100 μ g vs安慰剂）通过缓释肝素-藻酸盐微胶囊递送，植入缺血和存活但不可移植的心肌区域：24例接受冠状动脉旁路移植术的患者，除接受冠状动脉旁路移植术外，随机分为bFGF 10 μ g组（n = 8）、bFGF 100 μ g组（n = 8）和安慰剂组（n = 8）。没有治疗相关的不良事件，血清bFGF水平也没有升高。对所有患者进行了临床随访（16.0 +/- 6.8个月）。3例对照组患者心绞痛复发，其中2例需要再次血运重建。10 μ g bFGF组中有1例患者发生心绞痛，而100 μ g bFGF组中所有患者均无心绞痛。在基线和CABG后3个月的负荷核灌注成像显示安慰剂组的缺损尺寸有恶化的趋势（20.7 ± 3.7%至23.8 ± 5.7%，P = 0.06），10 μ g bFGF组无显著变化，100 μ g bFGF组有显著改善（19.2 ± 5.0%至9.1 ± 5.9%，P = 0.01）。磁共振评估的目标缺血区的一个子集的患者显示了一个趋势，减少在目标缺血：面积在100 μ g bFGF组（10.7 +/- 3.9%至3.7 +/-6.3%，P = 0.06）。结论-这项研究的bFGF在接受CABG的患者证明了安全性和可行性，这种模式的治疗患者的存活心肌，不能充分血运重建。
Background-Angiogenesis is a promising treatment strategy for patients who are not candidates for standard revascularization, because it promotes the growth of new blood vessels in ischemic myocardium.Methods and Results-We conducted a randomized, double-blind, placebo-controlled study of basic fibroblast growth factor (bFGF; 10 or 100 mu g versus placebo) delivered via sustained-release heparin-alginate microcapsules implanted in ischemic and viable but ungraftable myocardial territories in: patients undergoing CABG, Twenty-four patients were randomized to 10 mu g of bFGF (n = 8), 100 mu g of bFGF (n = 8), or placebo (n = 8), in addition to undergoing CABG, There were 2 operative deaths and 3 Q-wave myocardial infarctions. There were no treatment-related adverse events, and there was no rise in serum bFGF levels. Clinical follow-up was available for all patients (16.0 +/- 6.8 months). Three control patients had recurrent angina, 2 of whom required repeat revascularization. One patient in the 10-mu g bFGF group had angina,:whereas all patients in the 100-mu g bFGF group remained angina-free. Stress nuclear perfusion imaging at baseline and 3 months after CABG showed a trend toward worsening of the defect size in the placebo group (20.7 +/- 3.7% to:23.8 +/- 5.7%, P = 0.06), no significant change in the 10-mu g bFGF group, and significant improvement in the 100-mu g bFGF group (19.2 +/- 5.0% to 9.1 +/- 5.9%, P = 0.01). Magnetic resonance assessment of the target ischemic zone in a subset of patients showed a trend toward a reduction in the target ischemic:area in the 100-mu g bFGF group (10.7 +/- 3.9% to 3.7 +/- 6.3%, P = 0.06).Conclusions-This study of bFGF in patients undergoing CABG demonstrates the safety and feasibility of this mode of therapy in patients with viable myocardium that-cannot be adequately revascularized.