Weeraman Deshan, Jones Daniel A, Hussain Mohsin, Beirne Anne-Marie, Hadyanto Steven, Rathod Krishnaraj S, Whiteford James R, Reid Alice E, Bourantas Christos V, Ylä-Herttuala Seppo, Baumbach Andreas, Gersh Bernard J, Henry Timothy D, Mathur Anthony
Centre for Cardiovascular Medicine and Devices, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom.
Barts National Institute for Health and Care Research Biomedical Research Centre, Barts Heart Centre & Queen Mary University of London, London, United Kingdom.
J Soc Cardiovasc Angiogr Interv. 2023 Jan 2;2(1):100527. doi: 10.1016/j.jscai.2022.100527. eCollection 2023 Jan-Feb.
Refractory angina (RFA; limiting angina despite optimal medical therapy) is a growing, global problem, with limited treatment options. Therefore, we conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effect of proangiogenic growth factor therapy (in the form of vascular growth factors delivered either as recombinant proteins or gene therapy) in patients with RFA ineligible for revascularization.
We performed a meta-analysis (PROSPERO: CRD42018107283) of RCTs as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. A comprehensive search of the PubMed, CENTRAL, Embase, Cochrane, ClinicalTrials.gov and Google Scholar databases, as well as scientific session abstracts, were performed. The pooled outcomes included major adverse cardiac events (MACE), mortality, myocardial perfusion, and indices of angina severity (Canadian Cardiovascular Society angina class [CCS] and exercise tolerance). A prespecified subgroup analysis was performed for delivery method, vector, and protein type. The standardized mean difference (SMD) or odds ratio (OR) was calculated to assess relevant outcomes. We assessed heterogeneity using the χ and I tests.
We included 16 RCTs involving 1607 patients (1052 received proangiogenic growth factor therapy and 555 received a placebo or optimal medical therapy). Our analysis showed a significant decreased risk of MACE (OR, 0.72; 95% confidence interval [CI], 0.55-0.93) and significantly improved CCS class (SMD, -0.55; 95% CI, -1.10 to 0.00), but not mortality (OR, 0.66; 95% CI, 0.28-1.54) or exercise tolerance (SMD, 0.47; 95% CI, -0.14 to 1.09), in treated patients compared to those in the control group.
Proangiogenic growth factor therapy is a promising treatment option for RFA, with beneficial effects seen on MACE and CCS class. The results of ongoing trials are needed before it can be considered for clinical practice.
难治性心绞痛（RFA；尽管接受了最佳药物治疗仍有局限性心绞痛）是一个日益严重的全球性问题，治疗选择有限。因此，我们对随机对照试验（RCT）进行了系统评价，以评估促血管生成生长因子治疗（以重组蛋白或基因治疗形式递送的血管生长因子）对不符合血运重建条件的RFA患者的疗效。
我们按照系统评价和Meta分析的首选报告项目方法对RCT进行了Meta分析（PROSPERO：CRD42018107283）。对PubMed、CENTRAL、Embase、Cochrane、ClinicalTrials.gov和谷歌学术数据库以及科学会议摘要进行了全面检索。汇总的结果包括主要不良心脏事件（MACE）、死亡率、心肌灌注和心绞痛严重程度指标（加拿大心血管学会心绞痛分级[CCS]和运动耐量）。对递送方法、载体和蛋白类型进行了预先指定的亚组分析。计算标准化均数差（SMD）或比值比（OR）以评估相关结果。我们使用χ²和I²检验评估异质性。
我们纳入了16项RCT，涉及1607例患者（1052例接受促血管生成生长因子治疗，555例接受安慰剂或最佳药物治疗）。我们的分析显示，与对照组相比，治疗组患者发生MACE的风险显著降低（OR，0.72；95%置信区间[CI]，0.55-0.93），CCS分级显著改善（SMD，-0.55；95%CI，-1.10至0.00），但死亡率（OR，0.66；95%CI，0.28-1.54）或运动耐量（SMD，0.47；95%CI，-0.14至1.09）无显著改善。
促血管生成生长因子治疗是RFA的一种有前景的治疗选择，对MACE和CCS分级有有益影响。在可考虑将其应用于临床实践之前，需要等待正在进行的试验结果。
