Safety of paclitaxel-coated devices in patients with peripheral artery disease: an updated systematic review and meta-analysis of randomized controlled trials

Background: Paclitaxel-coated devices have been widely used to reduce restenosis in patients with peripheral artery disease (PAD). However, their long-term safety, particularly regarding mortality and amputation risks, remains controversial. Methods: statistic. Risk of bias was evaluated with the Cochrane tool. This PROSPERO-registered review (CRD420251155841) was conducted between September and December 2025. Findings: A total of 15 RCTs involving 5859 patients were included. No significant differences were observed in all-cause mortality between the paclitaxel and control groups at 1 year (RR: 1.04, 95% CI: 0.87-1.24), 2 years (RR: 1.28, 95% CI: 0.95-1.74), or 5 years (RR: 1.13, 95% CI: 0.93-1.38). Similarly, no significant differences in amputation rates were observed at 1 year (RR: 1.07, 95% CI: 0.88-1.31), 2 years (RR: 0.65, 95% CI: 0.34-1.24), or 5 years (RR: 1.03, 95% CI: 0.88-1.20). Paclitaxel-coated devices significantly reduced TLR at 1 year (RR: 0.64, 95% CI: 0.48-0.87) and 2 years (RR: 0.45, 95% CI: 0.38-0.54), but this benefit was not sustained at 5 years (RR: 0.81, 95% CI: 0.64-1.01). Primary patency at 2 years was significantly improved with paclitaxel devices (RR: 1.57, 95% CI: 1.24-1.99). Interpretation: This updated meta-analysis indicates that paclitaxel-coated devices are not associated with increased risks of all-cause mortality or major amputation for up to 5 years. Although these devices offer mid-term benefits in reducing TLR and improving patency, these advantages decrease over the long term. These findings support the continued use of paclitaxel-coated devices in selected patients with symptomatic femoropopliteal disease, while emphasizing the need for individualized decision-making and long-term clinical follow-up. Funding: None.