Safety and Efficacy of Endovascular Treatment Modalities for Below-the-Knee Arterial Disease: A Systematic Review and Network Meta-analysis

Abstract

Background:

Endovascular revascularization of below-the-knee lesions is a crucial treatment for patients with chronic limb-threatening ischemia (CLTI). However, the optimal approach to revascularizing infrapopliteal arteries remains uncertain. This study aims to compare the safety and efficacy outcomes of various endovascular treatment modalities for infrapopliteal artery disease and provide an evidence-based update through a network meta-analysis.

Methods:

We performed a systematic literature search in MEDLINE, EMBASE, and the Cochrane Database for randomized controlled trials published between January 01, 2005, and January 12, 2025. The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was prospectively registered in PROSPERO database (CRD42022323480). The primary safety outcome was major adverse events defined as a composite of all-cause death, major amputation, and any re-intervention of the target limb at 30 days. The primary efficacy outcomes included freedom from composite of major amputation, target lesion occlusion, and clinically driven target lesion revascularization (CD-TLR) and primary patency defined as freedom from binary restenosis and CD-TLR at 6 months. The network meta-analysis was conducted in the frequentist framework using random effects model and conventional percutaneous transluminal angioplasty (PTA) as the reference intervention. Treatment effects were reported as odds ratio (OR) with 95% confidence interval (CI) compared with conventional PTA and interventions were ranked using P-scores.

Results:

Twenty-three studies including 3091 patients treated with PTA, paclitaxel drug-coated balloons (DCB), drug-eluting stents (DES), bare metal stents (BMS), bioresorbable vascular scaffold (BVS), and atherectomy were included. There were no significant differences in the primary safety outcome between different treatment modalities. At 6 months, DCB, atherectomy with DCB, and DES produced the largest benefit for primary efficacy outcomes. DCB (OR, 3.68; 95% CI, 1.37–9.92) had a higher freedom from the primary composite, and atherectomy with DCB (OR, 7.65; 95% CI, 1.03–56.98) and DES (OR, 5.48; 95% CI, 1.54–19.49) had higher primary patency compared with PTA. At 12 months, the benefit of atherectomy with DCB was sustained for primary patency, and BVS was ranked first for freedom from the primary composite. There was no benefit of BMS compared with PTA at any timepoint.

Conclusions:

This network meta-analysis evaluating 7 endovascular treatment modalities provides evidence of improved efficacy outcomes with DCB, atherectomy with DCB, DES, and BVS compared with PTA for treating infrapopliteal lesions in patients with CLTI.

Clinical Impact

Local antiproliferative drug delivery, whether by balloon-expandable sirolimus/everolimus DES or paclitaxel DCB or everolimus BVS, is necessary to improve patency and efficacy outcomes for the treatment of infrapopliteal artery disease. Furthermore, combining atherectomy with drug delivery shows promising potential. Emerging endovascular targeted drug delivery therapies with limus-based DCB or scaffolds promise to provide greater drug transfer efficiency and a more effective therapeutic alternative that overcomes the limitations of metallic stents in one of the most challenging vascular beds.