Continuous intrafemoral artery infusion of urokinase improves diabetic foot ulcers healing and decreases cardiovascular events in a long-term follow-up study.

Introduction: Diabetic foot ulcer (DFU) is a disabling complication of diabetes mellitus. Here, we attempted to assess whether long-term intrafemoral artery infusion of low-dose urokinase therapy improved DFUs and decreased cardiovascular events in patients with DFUs.

Research design and methods: This trial was a single-center, randomized, parallel study. A total of 195 patients with DFU were randomized to continuous intrafemoral thrombolysis or conventional therapy groups. The continuous intrafemoral thrombolysis group received continuous intrafemoral urokinase injection for 7 days, and conventional therapy just received wound debridement and dressing change. Then, a follow-up of average 6.5 years was performed.

Results: Compared with conventional therapy, at the first 1 month of intervention stage, the ulcers achieved a significant improvement in continuous intrafemoral thrombolysis group including a complete closure (72.4% vs 17.5%), an improved ulcer (27.6% vs 25.8%), unchanged or impaired ulcer (0% vs 56.7%). During the 6.5-year follow-up, for the primary outcome of ulcer closure rate, continuous intrafemoral thrombolysis therapy obtained a better complete healing rate (HR 3.42 (95% CI 2.35 to 4.98, p<0.0001)). For the secondary outcome of cardiovascular disease events, continuous intrafemoral thrombolysis therapy had a lower incidence of cardiovascular events (HR 0.50 (95% CI 0.34 to 0.74, p<0.0001)). Importantly, intrafemoral thrombolysis therapy decreased the incidence of cardiovascular death (HR 0.42 (95%CI 0.20 to 0.89, p=0.0241)). Additionally, continuous intrafemoral thrombolysis therapy improved local skin oxygenation and peripheral neuropathy as well as glycolipid metabolic profiles when compared with conventional therapy group (p<0.05).

Conclusions: Continuous intrafemoral thrombolysis therapy has a better therapeutic efficacy to improve DFUs and decrease cardiovascular events.

Trial registration number: NCT01108120.