Graduate School, Beijing University of Chinese Medicine, Beijing, China.
Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Cardiovasc Ther. 2018 Oct;36(5):e12461. doi: 10.1111/1755-5922.12461. Epub 2018 Aug 15.
It is not clear whether treatment by vascular endothelial growth factor (VEGF) gene transfer can improve myocardial ischemia through a proangiogenesis mechanism and is effective against coronary artery disease (CAD). We aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared VEGF gene therapy and standard treatments in CAD.
We systematically searched the PubMed, Embase, and Cochrane databases and relevant references for RCTs (published up to May 2018; no language restrictions) and performed meta-analysis using both fixed and random effects models. Our primary outcome measures were mortality and serious cardiac events. The secondary outcome measures were follow-up left ventricular ejection fraction (LVEF), change in LVEF (ΔLVEF), and angina outcomes. The registration number is CRD42017058430.
Of 524 identified studies, 14 were eligible and were included in our analysis. At a mean follow-up of 6 months, VEGF gene therapy demonstrated a decreased risk of serious cardiac events (11.7% vs 21.2%, relative risk: 0.56; 95% confidence interval (CI): 0.37, 0.84; P = 0.005) and a slight improvement in follow-up LVEF (weighted mean difference: 1.95; 95%CI: 1.28, 2.62). Furthermore, VEGF gene therapy using adenoviral vectors showed more potential benefit in terms of the risk of serious cardiac events, ΔLVEF, and Canadian Cardiovascular Society angina class. Nevertheless, mortality and angina frequency scores were not different.
Vascular endothelial growth factor gene therapy appears to be safe and effective regarding serious cardiac events, with greater benefit when using adenoviral vectors. This meta-analysis highlights the need for further exploration in these areas.
目前尚不清楚血管内皮生长因子（VEGF）基因转导治疗是否可以通过促血管生成机制改善心肌缺血，以及是否对冠心病（CAD）有效。我们旨在对比较 CAD 中 VEGF 基因治疗和标准治疗的随机对照试验（RCT）进行系统评价和荟萃分析。
我们系统地检索了 PubMed、Embase 和 Cochrane 数据库以及相关参考文献（截至 2018 年 5 月发表，无语言限制），并使用固定效应模型和随机效应模型进行荟萃分析。我们的主要结局指标是死亡率和严重心脏事件。次要结局指标为随访左心室射血分数（LVEF）、LVEF 变化（ΔLVEF）和心绞痛结局。注册号为 CRD42017058430。
在 524 项确定的研究中，有 14 项符合纳入标准并纳入分析。在平均 6 个月的随访中，VEGF 基因治疗可降低严重心脏事件的风险（11.7%比 21.2%，相对风险：0.56；95%置信区间（CI）：0.37，0.84；P=0.005），并略微改善随访 LVEF（加权均数差：1.95；95%CI：1.28，2.62）。此外，使用腺病毒载体的 VEGF 基因治疗在严重心脏事件风险、ΔLVEF 和加拿大心血管学会心绞痛分级方面具有更大的获益潜力。然而，死亡率和心绞痛频率评分无差异。
VEGF 基因治疗在严重心脏事件方面似乎是安全有效的，使用腺病毒载体时获益更大。本荟萃分析强调了在这些领域进一步探索的必要性。
