Emerging Sirolimus-Based Drug-Coated Technologies for Femoropopliteal Disease: A Systematic Review

Abstract

Purpose:

To systematically review the current evidence on the use of sirolimus-coated endovascular devices for the treatment of femoropopliteal peripheral artery disease (PAD), focusing on efficacy, safety, and clinical feasibility.

Materials and Methods:

A comprehensive systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, and Medline were searched from inception to July 2025, along with ClinicalTrials.gov and the EU Clinical Trials Register. Eligible studies included clinical trials in humans evaluating sirolimus-eluting balloons or sirolimus-eluting stents (DES) for femoropopliteal lesions. Data extracted included patient characteristics, lesion complexity, follow-up duration, primary patency (PP), freedom from clinically-driven target lesion revascularization (CD-TLR), and bailout stenting rates.

Results:

Fifteen studies encompassing 2960 patients (2439 with femoropopliteal disease) were included. Randomized controlled trials were limited (SIROCCO I–II, SIRONA, ASCLEPIOS), with most data derived from prospective registries. Six studies incorporated independent core laboratory adjudication. Mean lesion length ranged from 5.8 to 27.7 cm, with total occlusions reported in up to 100% of cases and severe calcification (PACSS grade 4) in up to 48%. At 12 months, primary patency ranged from 58.1% to 94%, while freedom from CD-TLR varied between 74.3% and >95%. Three-year outcomes demonstrated sustained efficacy, with PP of 74.7% and CD-TLR freedom of 92.9% in selected studies. Bailout stenting was generally low (0%–38%). Early sirolimus DES trials did not demonstrate superiority over bare stents, but newer devices (eg, NiTiDES) showed improved outcomes. No sirolimus-specific adverse safety signals have been reported; however, long-term data beyond 36 months are missing.

Conclusion:

Sirolimus-coated devices offer a promising alternative to paclitaxel-based technologies for femoropopliteal PAD, with encouraging efficacy and a favorable short- to mid-term safety profile. Outcomes are comparable to those of paclitaxel devices, even in complex lesions. Nevertheless, current evidence is limited by heterogeneous study designs, small sample sizes, and relatively short follow-up. Larger randomized trials with independent adjudication and extended surveillance are required to define the long-term safety and clinical role of sirolimus in femoropopliteal interventions.

Clinical Impact

This systematic review consolidates the emerging clinical evidence on sirolimus-coated technologies for femoropopliteal disease, offering clinicians a structured appraisal of efficacy and safety across devices and lesion complexities. In the context of persistent debate surrounding paclitaxel, sirolimus represents a mechanistically distinct, cytostatic alternative with encouraging short- and mid-term outcomes and no current safety signal. For practicing interventionists, these findings support the cautious integration of sirolimus-coated balloons and newer-generation stents into daily practice, particularly in complex lesions. The innovation lies in controlled drug delivery platforms leveraging mTOR inhibition, potentially combining antiproliferative efficacy with improved vascular healing. Larger randomized trials will determine their definitive role in treatment algorithms.