Sirolimus Versus Paclitaxel-Coated Balloons for the Treatment of Femoropopliteal Artery Disease: A Systematic Review.

BACKGROUND

Femoropopliteal revascularization remains challenged by high restenosis rates, and while paclitaxel-coated balloons (PCB) have demonstrated efficacy, emerging long-term mortality concerns have shifted interest toward sirolimus-coated balloons (SCB) as a mechanistically distinct, cytostatic alternative. This systematic review and meta-analysis aims to comprehensively evaluate their comparative safety and efficacy.

METHODS

A systematic search of PubMed, Scopus, Embase, Cochrane Library, ClinicalTrials.gov, and WHO-ICTRP was conducted from inception to June 2026, identifying randomized controlled trials directly comparing SCB vs PCB. Poolable outcomes were meta-analyzed using a random-effects model, with results expressed as risk ratios and 95% confidence intervals; remaining outcomes were narratively synthesized. Methodological quality was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated using the GRADE framework.

RESULTS

3 RCTs enrolling 558 participants and two registered trial protocols were included. Narrative synthesis demonstrated similar primary patency (75.1% vs. 76.8%), binary restenosis (18.2% vs. 18.1%), Rutherford classification improvement (88.5% vs. 91.5%), target lesion revascularization (7.3% vs. 6.4%), target vessel revascularization (9.5% vs. 7.3%), hemodynamic improvement (70.6% vs. 70.9%), and major amputation (0.5% vs. 0.5%) between both groups. All-cause mortality (3.9% vs. 2.1%) and major adverse events (41.2% vs. 36.5%) were numerically higher with SCBs in the only trial reporting these endpoints. Meta-analysis demonstrated no significant difference in primary patency (RR = 0.98, 95% CI: 0.88-1.08; p = 0.615; I2 = 0%) or Rutherford classification improvement (RR = 0.98, 95% CI: 0.92-1.05; p = 0.633; I2 = 0%) between SCBs and PCBs.

CONCLUSION

Sirolimus-coated balloons demonstrate efficacy and safety comparable to paclitaxel-coated balloons for femoropopliteal artery disease, with no significant differences in primary patency or other clinical outcomes. While preliminary mechanistic findings favor sirolimus, larger studies with longer follow-up are needed to determine whether these biological advantages translate into sustained clinical benefit.