Five-Year Prognostic Outcomes After Paclitaxel-Coated Balloon Treatment According to Chronic Limb-Threatening Ischaemia Status: Insights From the BIOLUX P-III Registry

Background: Chronic limb-threatening ischaemia (CLTI) carries a high risk of death, limb loss, and impaired functional recovery despite revascularisation. Drug-coated balloons may reduce restenosis and repeat intervention after infrainguinal endovascular therapy, but long-term safety and effectiveness data in patients with CLTI remain limited. Methods: We performed a prespecified subgroup analysis of BIOLUX P-III, a prospective international post-market all-comers registry evaluating the Passeo-18 Lux paclitaxel-coated balloon for infrainguinal peripheral artery disease. Outcomes were compared between patients with and without CLTI through 60 months. Endpoints included freedom from major adverse events, clinically driven target-lesion revascularisation, major target-limb amputation, amputation-free survival and all-cause mortality. Time-to-event outcomes were analysed using Kaplan-Meier methods. Because follow-up completeness declined substantially by 60 months, late estimates were interpreted in the context of censoring, attrition and competing mortality. Results: Among 877 treated patients, 328 (37.4%) had CLTI. Technical success exceeded 98% in both groups. Patients with CLTI had greater baseline comorbidity, more advanced limb threat and more frequent below-the-knee disease. At 60 months, freedom from clinically driven target-lesion revascularisation was 85.3% in patients with CLTI and 78.3% in those without CLTI ( P = .59), and freedom from major adverse events was similar (76.5% vs 74.3%; P = .13). In contrast, 5-year survival was substantially lower in patients with CLTI (47.9% vs 76.7%; P < .001). Freedom from major target-limb amputation was lower (93.3% vs 99.3%; P < .001), and amputation-free survival was reduced (47.1% vs 75.7%; P < .001). Patients with CLTI received a lower cumulative paclitaxel dose despite higher mortality. Conclusions: Passeo-18 Lux treatment was associated with preserved lesion-level durability through 5 years, but CLTI identified a high-risk prognostic phenotype with poor survival and limb outcomes. These findings suggest that long-term outcomes in CLTI are influenced by systemic comorbidity, early limb vulnerability, competing mortality and wound-related factors beyond lesion-level device performance alone. Clinical Impact This study provides clinically relevant insights into the long-term outcomes of patients with chronic limb-threatening ischaemia (CLTI) undergoing endovascular revascularisation with drug-coated balloons. Despite high procedural success, patients with CLTI experience substantially greater long-term mortality and adverse limb outcomes than those with intermittent claudication. These findings highlight the importance of recognising CLTI as a high-risk clinical phenotype requiring comprehensive cardiovascular risk reduction, multidisciplinary management, and structured postprocedural surveillance. The study’s principal contribution is its evaluation of five-year outcomes in a real-world, all-comers population, providing valuable evidence to inform patient counselling, individualised treatment strategies, and long-term clinical decision-making.