OBJECTIVE:To perform a systematic review and meta-analysis evaluating the prognostic utility of the Global Limb Anatomical Staging System (GLASS) classification in patients with chronic limb-threatening ischemia, and to determine which intervention, endovascular or open bypass, is associated with superior outcomes in patients classified as GLASS III. METHODS:We conducted a systematic review and meta-analysis using PubMed, Scopus, and Cochrane Central from inception through October 2025. Outcomes compared across GLASS stages included immediate technical success (ITS) of endovascular procedures, overall survival, amputation-free survival, limb salvage, freedom from major adverse limb events (MALE), and limb-based patency (LBP). For patients with GLASS III disease, we directly compared endovascular vs surgical bypass revascularization for overall survival, freedom from MALE, and limb salvage. RESULTS:We included 17 studies in the meta-analysis, comprising 5290 patients and 5492 limbs: 945 (17.2%) GLASS I, 1431 (26.1%) GLASS II, and 3116 (56.7%) GLASS III. Compared with GLASS I, GLASS II presented a significantly higher hazard for LBP failure [hazard ratio (HR), 1.53; 95% confidence interval (CI), 1.06-2.20; P = .032] and major amputation (endovascular only; HR, 1.45; 95% CI, 1.13-1.86). When comparing GLASS III with GLASS I, GLASS III had significantly higher hazard for mortality (HR, 1.28; 95% CI, 1.06-1.56; P = .021), MALE (HR, 1.36; 95% CI, 1.02-1.83; P = .042), and LBP failure (HR, 2.23; 95% CI, 1.56-3.19; P = .003). GLASS I presented a significantly higher ITS rate compared with GLASS II [risk ratio (RR), 1.03; 95% CI, 1.01-1.05; P = .016] and GLASS III (RR, 1.24; 95% CI, 1.09-1.41; P = .005). GLASS II also showed a significantly higher ITS rate compared with GLASS III (RR, 1.20; 95% CI, 1.04-1.38; P = .017). No other comparisons across GLASS stages were statistically significant. Among patients classified as GLASS III, we found an increased hazard of MALE in the endovascular group compared with open bypass surgery (HR, 1.88; 95% CI, 1.35-2.61; P = .015). No significant differences were identified between endovascular and surgical bypass revascularization for other outcomes. CONCLUSIONS:This meta-analysis demonstrates that increasing GLASS anatomical severity is associated with progressively lower ITS following endovascular intervention and increased hazard of LBP failure across all revascularization strategies in patients with chronic limb-threatening ischemia. Patients classified as GLASS I, with low complexity anatomies, had a lower mortality and MALE hazard compared with those with high-complexity disease (GLASS III). Among patients classified as GLASS III, endovascular therapy is associated with an increased hazard for MALE compared with bypass surgery.
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