A Systematic Review and Meta-Analysis of Prognosis and Revascularization Strategies in Chronic Limb-Threatening Ischemia According to the Global Limb Anatomical Staging System.

Abstract

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 (CLTI), and to determine which intervention, endovascular or open bypass, is associated with superior outcomes for GLASS III patients. 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 (OS), amputation-free survival (AFS), limb salvage (LS), freedom from major adverse limb events (FF-MALE), and limb-based patency (LBP). For patients with GLASS III disease, we directly compared endovascular versus surgical bypass revascularization for OS, FF-MALE, and LS. We included 17 studies in the meta-analysis, comprising 5,290 patients and 5,492 limbs: 945 (17.2%) GLASS I, 1,431 (26.1%) GLASS II, 3,116 (56.7%) GLASS III. Compared with GLASS I, GLASS II presented a significantly higher hazard for LBP failure (HR 1.53; 95% CI 1.06 - 2.20; p = 0.032) and major amputation (endovascular only) (HR 1.45; 95% CI 1.13 - 1.86). When comparing GLASS III to GLASS I, GLASS III had significantly higher hazard for mortality (HR 1.28; 95% CI 1.06 - 1.56; p = 0.021) and MALE (HR 1.36; 95% CI 1.02 - 1.83; p = 0.042), LBP failure (HR 2.23; 95% CI 1.56 - 3.19, p = 0.003). GLASS I presented a significantly higher ITS rate compared to GLASS II (RR 1.03; 95% CI 1.01 - 1.05; p = 0.016) and GLASS III (RR 1.24; 95% CI 1.09 - 1.41; p = 0.005). GLASS II also showed a significantly higher ITS rate compared to GLASS III (RR 1.20; 95% CI 1.04 - 1.38; p = 0.017). No other comparisons across GLASS stages were statistically significant. Among GLASS III patients, we found an increased hazard of MALE in the endovascular group compared to open bypass surgery (HR 1.88; 95% CI 1.35 - 2.61; p = 0.015). No significant differences were identified between endovascular and surgical bypass revascularization for other outcomes. 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 CLTI. GLASS I patients, with low complexity anatomies, had a lower mortality and MALE hazard compared with those with high-complexity disease (GLASS III). Among GLASS III patients, endovascular therapy is associated with an increased hazard for MALE compared to bypass surgery.