Gene therapy in peripheral arterial disease: a systematic review and meta-analysis of randomized, controlled trials

Abstract

Background: Beyond pharmacological, endovascular and surgical treatment strategies for peripheral arterial disease (PAD), therapeutic angiogenesis has been advocated to relieve symptoms and support limb salvage, in particular in patients with critical limb ischemia (CLI). We aimed to systematically review RCTs of gene therapy in PAD. Methods and material: A systematic search of electronic databases was performed to identify RCTs studying local administration of proangiogenic growth factors (VEGF, FGF, HGF, Del-1, HIF-1alpha) using plasmid or viral gene transfer by intraarterial or intramuscular injections. Outcomes of interest comprised all-cause mortality, amputations, ulcer healing, walking distance and ankle-brachial index. If feasible, standard meta-analysis should be performed with subgroup analysis for claudicants and patients with CLI. Results: The systematic search yielded 12 RCTs for analysis from 1163 citations. In total, 1494 patients (29% females) were included with the majority suffering from CLI (64%). Various endpoints were improved by single studies but non by a majority of studies (see Table 1). Meta-analysis showed neither a significant benefit nor harm for gene therapy when synthesizing data for all-cause mortality (OR 0.88, 95% CI 0.62-1.26) amputations (OR 0.64, 95% CI 0.31-1.31) or ulcer healing (OR 1.79, 95% CI 0.8-4.01). No differences were seen between patients with intermittent claudication or CLI. View this table: Table 1. Results of gene therapy studies Conclusion: Despite promising results in single studies, no clear benefit could be identified for gene therapy in PAD patients.