Sirolimus Versus Paclitaxel Drug‐Coated Ballons for Femoropopliteal Disease: The LIMUS FLOW Trial

BACKGROUND: Drug-coated balloon treatment is the recommended strategy for endovascular peripheral artery disease treatment. Besides proliferation and migration of smooth muscle cells, endothelial dysfunction and inflammation are known contributors in the restenosis process. Sirolimus and paclitaxel are both antirestenotic agents, exerting different pharmacomechanic properties. METHODS: We investigated the differential effects of sirolimus- and paclitaxel-coated balloons (SCBs and PCBs, respectively) in the endovascular treatment of severe PAD on endothelial function and inflammation. Clinical outcomes were also assessed. LIMUS FLOW Trial (Sirolimus Versus Paclitaxel Drug-Coated Ballons for Femoropopliteal Disease: The LIMUS FLOW Randomized Trial) was a proof-of-concept investigator-initiated randomized controlled trial with 70 patients randomized to SCBs or PCBs. Endothelial function restoration was assessed via endothelial-dependent vasomotion measured by flow mediated dilatation of the superficial femoral artery. Inflammatory markers, perfusion, primary patency, and target lesion revascularization were evaluated. The improvement in endothelial function was associated with reduced inflammatory markers following sirolimus application at 1-month follow-up. No differences were observed for primary patency or freedom from target lesion revascularization between the groups after 12 months. CONCLUSIONS: LIMUS FLOW explores a novel concept to achieve a more profound mechanistic understanding of vasomotion restoration after application of drug-coated balloons. Improved endothelial function restoration through 12 months, reduction of inflammatory markers through 30 days, with no difference in clinical outcomes, were observed following SCBs versus PCBs. REGISTRATION: URL: www.clinicaltrials.gov; Unique identifier: NCT05450042.