Clinical and economic burden of major lower-limb amputations attributable to peripheral artery disease in Italy: A nationwide analysis

Peripheral artery disease (PAD) represents a major cause of non-traumatic lower-limb amputation and is associated with substantial morbidity, mortality, and healthcare costs. Despite advances in medical and revascularization therapies, major amputations remain frequent, and comprehensive nationwide estimates of their clinical and hospital-related economic burden within the Italian National Health Service (SSN) are limited. The objectives of this study were to estimate the hospital-related economic burden of major lower-limb amputations attributable to PAD in Italy and to assess revascularization patterns and in-hospital mortality within the SSN. We conducted a nationwide observational study using the Italian National Hospital Discharge Database. Acute hospital discharges between 2015 and 2021 with a major lower-limb amputation and Diagnosis Related Group 113 were identified. Inpatient volumes, length of stay, and costs were estimated by amputation level. A longitudinal cohort of patients amputated between 2015 and 2017 was followed for two years before and after the index hospitalization to assess prior revascularization and in-hospital mortality using age- and sex-adjusted Cox models. A total of 26,417 PAD-attributable major amputations were identified, 75.6% of which were above-knee procedures. Cumulative inpatient expenditure reached €294 million, corresponding to over 511,000 hospital days. Only 46.0% of patients underwent revascularization before amputation. In-hospital mortality increased steeply within the first six months post-amputation and remained higher after above-knee procedures and among patients with diabetes, reaching 16-25% at 180 days and 23-34% at two years. Major lower-limb amputation remains a severe and costly outcome of PAD in Italy. Improved implementation of guideline-recommended PAD management is needed to reduce avoidable amputations and their economic burden on the SSN.