Time to Wound Healing and Major Adverse Limb Events in Patients with Critical Limb Ischemia Treated with Endovascular Revascularization

Background: There are few studies that quantify the impact of time to wound healing on outcomes after endovascular revascularization of critical limb ischemia (CLI). Methods: In this retrospective study, 179 patients with CLI and tissue loss were assessed for adverse events after endovascular therapy. Associations between time to wound healing and outcomes were determined via Cox proportional hazards analysis. The long-term probability of events was assessed with Kaplan-Meier analysis. The primary end point was major adverse limb events (MALE-major amputation, surgical endarterectomy, or bypass). Secondary end points were major amputation, need for repeat endovascular therapy, and mortality. Results: After multivariable adjustment for time-dependent wound healing, age, renal function, diabetes, and Rutherford class, independent predictors of MALE included the presence of an un-healed wound (hazard ratio [FIR], 5.2; 95% confidence interval (CI), 2.3-11.8; P < 0.0001) and creatinine >= 2.0 (HR, 2.4; 95% CI, 1.4-4.3; P = 0.003). On Kaplan-Meier analysis, the probability of MALE was greater in patients with unhealed wounds compared with healed wounds (log-rank P < 0.0001). Patients whose wounds healed within 4 months had a lower probability of MALE than patients who did not heal by 4 months (log-rank, P = 0.04). Unhealed wounds were also independently associated with major amputation (HR, 9.0; 95% CI, 2.6-31.1; P = 0.0004), and patients whose wounds healed by 3 months had less major amputation (log-rank, P = 0.04). Unhealed wounds were independently associated with increased risk of mortality (HR, 42.7; 95% CI, 5.7-319.0; P = 0.002) but not repeat revascularization. Conclusions: Unhealed wounds are an independent risk factor for MALE, major amputation, and mortality after endovascular treatment of CLI. Wound healing within 3 months is associated with less risk of major amputation, and within 4 months less risk of MALE. A focus should be on achieving wound healing as fast as possible in this population.