Editor's Choice - Association Between Anatomical Patterns of Arterial Occlusive Disease and Endovascular Outcomes in the BEST-CLI Trial Supports the Use of the Global Limb Anatomic Staging System

OBJECTIVE: This study aimed to retrospectively apply a modified Global Limb Anatomic Staging System (GLASS) framework of infrainguinal arterial disease to patients enrolled in the Best Endovascular vs. Best Surgical Therapy in patients with Critical Limb Ischemia (BEST-CLI) trial to assess its validity for limb based outcomes and its utility in guiding the choice between endovascular therapy (ENDO) and open surgical bypass (OPEN). METHODS: This was a secondary analysis of the BEST-CLI clinical trial dataset. The BEST-CLI trial randomised 1 830 patients with chronic limb threatening ischaemia to ENDO or OPEN revascularisation. Baseline arterial anatomy from case report form data was evaluated using a modified GLASS construct to classify femoropopliteal and infrapopliteal disease severity. Kaplan-Meier analyses and Cox proportional hazards models were used to assess associations between modified GLASS stage, treatment modality, and outcomes including major adverse limb events (MALEs), re-intervention, and amputation. RESULTS: Modified GLASS stages 1, 2, and 3 were assigned to 12.4%, 24.5%, and 63.1% of trial participants, respectively. The technical failure rate in patients in the ENDO group was 11.1%, 15.4%, and 17.5% in modified GLASS stages 1, 2, and 3, respectively. In ENDO, higher GLASS stage was associated with worse MALE free survival and increased re-intervention risk. No association between GLASS stage and limb based outcomes was observed in OPEN. When comparing ENDO vs. OPEN using Cox models with inverse propensity weighting, OPEN conferred superior limb outcomes in modified GLASS stage 2 and 3 patients, with fewer major re-interventions (hazard ratio [HR] 0.24, 95% confidence interval [CI] 0.15 - 0.40; p < .001 and HR 0.37, 95% CI 0.29 -0.47; p < .001) and amputations (HR 0.57, 95% CI 0.38 - 0.87; p = .009 and HR 0.62 95% CI 0.47 - 0.81; p = .001). Modified GLASS stage was not associated with all cause death in either group. CONCLUSION: This study validated GLASS, even in a modified format, as a predictor of limb based outcomes in endovascular therapy and highlighted its limited relevance in predicting outcomes after open bypass. GLASS should be incorporated into clinical decision making and trial designs, particularly to guide the revascularisation strategy in patients with complex occlusive disease (GLASS stage 3).