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A Systematic Review and Meta-Analysis of Growth Factor Therapy in Patients with Chronic Limb-Threatening Ischemia

cardiology
vascular-medicine

Abstract

Background.

Atherosclerosis is a common disease that results in narrowing or blockage of arteries in the limbs, thereby causing peripheral artery disease. The worst type of peripheral artery disease is chronic limb-threatening ischemia. Despite therapeutic angiogenesis being regarded as a possible treatment option, the effectiveness of this approach among patients with chronic limb-threatening ischemia remains questionable. This meta-analysis attempts to evaluate the clinical benefits of growth factor therapy to systematically improve the outcomes of chronic limb-threatening ischemia patients.

Methods.

This analysis involved a systematic search of the Cochrane Library, EMBASE and PubMed databases between their start dates and January 15, 2026. There were no language limitations. We used stringent inclusion criteria because we included only randomized controlled trials. In the case of discontinuous variables, we determined the risk ratios. In the case of continuous variables, the mean difference or the standardized mean difference was used.

Results.

In total, 2240 records were obtained, and 14 randomized controlled trials including 1696 patients satisfied the inclusion criteria. The results indicated that growth factor therapy markedly improved ulcer healing (RR = 1.99; 95% CI: 1.47–2.69) and visual analog scale scores at 3 months (MD = −1.12; 95% CI: −1.69–−0.55). However, no significant differences were found in the major amputation rate (RR = 0.70, 95% CI: 0.45–1.10), all-cause mortality (RR = 0.89, 95% CI: 0.65–1.23), transcutaneous oxygen pressure at 6 months (MD = −1.27, 95% CI: −2.53–0.00), pain score at 6 months (SMD = −0.56, 95% CI: −1.26–0.15), the ankle–brachial index at 3 months (MD = 0.03, 95% CI: −0.04–0.10), or the ankle–brachial index at 6 months (MD = 0.01, 95% CI: −0.05–0.07).

Conclusion.

Growth factor therapy appears to be effective at promoting ulcer healing and pain relief in patients with chronic limb-threatening ischemia. Moreover, a combination of growth factors may offer additional benefits. These results should be considered cautiously, as the available evidence is of low quality. More high-quality randomized controlled trials are needed to clearly determine the effectiveness of these treatments.

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