A Systematic Review and Meta-Analysis of the Efficacy and Safety of Limus-Coated/Eluting Devices in Peripheral Arterial Disease.

Abstract

Aim: Limus-based balloons, stents, and scaffolds are alternatives to paclitaxel-coated devices in peripheral endovascular treatment. This study aims to review contemporary evidence on the efficacy and safety of limus-coated devices in the treatment of lower extremity peripheral arterial disease (PAD).

Methods: A systematic literature review was performed using PubMed, Web of Sciences, OvidSP, and EMBASE, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Efficacy endpoints were primary patency (PP), freedom from clinically driven target lesion revascularization (CD-TLR) and Rutherford-Becker improvement; safety endpoints included target limb amputation and all-cause mortality.

Results: From a primary search of 453 articles between 27th June 2002 to 15th September 2024, 30 publications, among which were 27 prospective trials, 10 multicenter studies and 11 double-arm studies, with 2325 patients were analyzed. The numbers for above-the-knee (ATK) limus-balloons, stents, scaffolds and below-the-knee (BTK) limus-balloons, stents, scaffolds were 76, 333, 35, 55, 1445, 381 respectively. With a mean 12-month follow-up, PP for ATK lesions was 86.50% for sirolimus-coated balloons (SCB), 86.80% for sirolimus-eluting stents (SES), 72.60% for everolimus-eluting stents (EES), 86.20% for everolimus bioresorbable vascular scaffold (EBVS); whereas PP for BTK lesions was 72.60%, 73.20%, 71.60 and 83.80% respectively. Absence of CD TLR for ATK lesions was 96.50%, 95.50%, 87.60%, 89.20% respectively; meanwhile 84.90%, 75.80%, 87.70%, 94.30% for BTK lesions respectively. Rutherford-Becker improvement with 86.70%, 84.50%, 79.80 and 90.80% were seen in ATK lesions respectively, similarly, 76.50%, 81.90%, 79.50%, 92.30% respectively were observed in BTK lesions. Efficacy and clinical outcomes of SES, EES and EBVS in BTK lesions were significantly superior, where vascular complications had no proven significant difference regardless of lesion locations nor device types.

Conclusion: Limus-coated/eluting balloons, stents, and scaffolds are safe adjuncts and potentially superior alternative in endovascular treatment for lower extremity PAD, especially well proven in BTK lesions. However, more statistically significant evidence is recommended to validate the long-term efficacy on ATK lesions and overall use of non-SES devices regardless of locations.

Clinical impact: Limus (siro-, zotaro-, evero-, bio-, amphi-, tacrolimus) have potent antiproliferative effects in atherosclerosis. This systematic review analyzes evidence for the efficacy and safety of limus devices (balloons, stents, and scaffolds) in the treatment of femoropopliteal and below-the-knee PAD. There were 5 single-arm studies with 309 patients on femoropopliteal disease, and 11 studies with 679 patients on below-the knee (BTK) diseases. The overall primary patency rate, significant freedom from target lesion revascularization and improvement in Rutherford-Becker classification were high. Certain limus devices have shown to be superior to non-limus devices. Limus scaffolds are new developments with promising short-term results.