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Review
. 2023 Jan 2;2(1):100527.
doi: 10.1016/j.jscai.2022.100527. eCollection 2023 Jan-Feb.

Proangiogenic Growth Factor Therapy for the Treatment of Refractory Angina: A Meta-analysis

Deshan Weeraman  1   2   3 , Daniel A Jones  1   2   3 , Mohsin Hussain  2   3 , Anne-Marie Beirne  1   3 , Steven Hadyanto  2 , Krishnaraj S Rathod  1   2   3 , James R Whiteford  4 , Alice E Reid  1 , Christos V Bourantas  1   2   3 , Seppo Ylä-Herttuala  5 , Andreas Baumbach  1   2   3 , Bernard J Gersh  6 , Timothy D Henry  7 , Anthony Mathur  1   2   3
Affiliations
Review

Proangiogenic Growth Factor Therapy for the Treatment of Refractory Angina: A Meta-analysis

Deshan Weeraman et al. J Soc Cardiovasc Angiogr Interv. .

Abstract

Background: 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.

Methods: 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 χ2 and I2 tests.

Results: 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.

Conclusions: 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.

Keywords: angiogenesis; chronic myocardial ischemia; gene therapy; meta-analysis; refractory angina.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Risk-of-bias assessment.
Figure 2
Figure 2
Study flow chart: Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram illustrating the study selection process for the meta-analysis. RCT, randomized controlled trial; RFA, refractory angina.
Figure 3
Figure 3
Proangiogenic growth factor therapy and risk of mortality. Forest plot displays the odds ratio (OR) and 95% CI. df, degrees of freedom; M-H, Mantel-Haenszel.
Figure 4
Figure 4
Proangiogenic growth factor therapy and the risk of major adverse cardiovascular events. Forest plot displays the odds ratio (OR) and 95% CI. df, degrees of freedom; M-H, Mantel-Haenszel.
Figure 5
Figure 5
Forest plot showing the standardized difference between the mean changes in exercise tolerance from baseline and mean value at the endpoint in patients who received proangiogenic growth factor therapy versus those who received maximal medical therapy. Forest plot displays Standard Mean Difference (SMD) and 95% CI. df, degrees of freedom; M-H, Mantel-Haenszel.
Figure 6
Figure 6
Forest plot showing the standardized difference between the mean changes in Canadian Cardiovascular Society class from baseline and mean value at the endpoint in patients who received proangiogenic growth factor therapy versus those who received maximal medical therapy. Forest plot displays standard mean difference (SMD) and 95% CI. df, degrees of freedom; M-H, Mantel-Haenszel.
Figure 7
Figure 7
Delivery route and risk of major adverse cardiovascular events. Forest plot displays the odds ratio (OR) and 95% CI. df, degrees of freedom; M-H, Mantel-Haenszel.
Figure 8
Figure 8
Delivery route and risk of mortality. Forest plot displays the summary the odds ratio (OR) and 95% CI. df. degrees of freedom; M-H. Mantel-Haenszel.
Figure 9
Figure 9
Vector type and the risk of major adverse cardiovascular events. Forest plot displays the odds ratio (OR) and 95% CI.
Figure 10
Figure 10
Vector type and risk of mortality. Forest plot displays the odds ratio (OR) and 95% CI.
Central Illustration
Central Illustration
The main findings of this meta-analysis of proangiogenic growth factor therapy for refractory angina. CCS, Canadian Cardiovascular Society Angina Score; CI, confidence interval; MACE, major adverse cardiac event; OR, odds ratio; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RCT, randomized controlled trial; SMD, standard mean difference.
See this image and copyright information in PMC

References

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