Contemporary Outcomes of Distal Lower Extremity Bypass for Chronic Limb-Threatening Ischemia and A Model-Based Comparison With Autologous Bone Marrow-Derived Cell Therapy for Limb Preservation

The standard of therapy for chronic limb-threatening ischemia (CLTI) is revascularization. However, for patients for whom below-the-knee bypass is indicated, an autologous great saphenous vein (GSV), the optimal conduit, might not be available. For these patients, an alternative conduit, such as a synthetic or cryopreserved biologic graft, will be necessary. Contemporary outcomes of distal bypass with these suboptimal conduits have not been well described, and recent advances in novel nonoperative management such as autologous bone marrow cell (BMC) therapy warrant a comparative analysis as a potential alternative for limb preservation. Data were obtained from the Vascular Quality Initiative (VQI) registry and from a randomized clinical trial of BMC therapy. The incidence of major amputation after distal bypass was estimated for the VQI cohort by conduit type using a nonparametric survival analysis. A Cox proportional hazards model was then fit to the pooled VQI data and clinical trial data to adjust for differences in baseline risk factors. Hazard ratios (HRs) were estimated for the risk of major amputation after distal bypass or BMC therapy. At 365 days, the estimated cumulative incidence of major amputation, with death as a competing risk, was 25% after distal bypass with a cryopreserved biologic conduit, 13% with a prosthetic graft, and 9% for a GSV conduit (Fig 1). The model found a significant interaction between age and treatment. Compared with bypass with a biologic graft, the HRs for major amputation after bypass with a GSV were 0.41, 0.41, 0.42, and 0.42 (P < .0001 for all) at age 55, 60, 65, and 70 years, respectively. The HRs after bypass with a prosthetic graft at age 55, 60, 65, and 70 years were 0.68 (P = .0043), 0.67 (P = .0004), 0.65 (P < .0001), and 0.64 (P < .0001), respectively. The corresponding HRs for autologous cell therapy were 0.22 (P = .0005), 0.34 (P = .0011), 0.52 (P = .0196), and 0.76 (P = .3677; Fig 2). The risk of major amputation after distal bypass was lowest in patients with a GSV conduit and greatest with a cryopreserved graft. BMC therapy was estimated to decrease the risk of amputation compared with distal bypass with a prosthetic graft in patients aged 55 and 60 years and compared with biologic grafts in patients aged 55, 60, and 65 years. These data suggest that BMC therapy might be superior to these suboptimal grafts in preventing amputation in younger patients.Fig 2Hazard ratio (HR) of major amputation and 95% confidence interval for each treatment group compared with biologic bypass and adjusted for age. BMC, Bone marrow cell; GSV, great saphenous vein.View Large Image Figure ViewerDownload Hi-res image Download (PPT)