Real-world outcomes of above-knee amputation: Investigating the impact of peripheral arterial disease

Objective: Above-knee amputation (AKA), or transfemoral amputation, represents a highly morbid surgical procedure, typically performed in patients with irreversible limb compromise due to peripheral arterial disease, diabetes, trauma, or malignancy. Despite prior declines, U.S. incidence of AKA has risen 4% annually since 2012, paralleling an aging population and evolving comorbid risk profiles. Given its profound functional, psychosocial, and systemic implications, a contemporary understanding of real-world outcomes is essential. This study evaluated demographic characteristics, preoperative comorbidities, and postoperative complications of patients undergoing AKA using the TriNetX global health research network, comparing large-scale patient data with published literature to identify gaps between controlled research and clinical practice. Methods: A retrospective cohort analysis was performed using deidentified electronic health records within TriNetX, identifying approximately 23,000 patients who underwent AKA via Current Procedural Terminology codes 27590, 27594, and 27596. Demographics, preoperative comorbidities, and postoperative outcomes—including stroke, myocardial infarction, infection, venous thromboembolism, contralateral limb amputation, and mortality—were assessed longitudinally and compared with systematically reviewed literature cohorts (n = 56-2879 patients). Statistical comparisons were conducted using two-proportion z tests (P < .05). Results: TriNetX patients were younger (70 vs 75 years) and more often male (61.3% vs 47.4%) than literature cohorts. Compared with literature, TriNetX showed higher rates of chronic kidney disease (39% vs 23.9%) and end-stage renal disease (16% vs 12.9%) but lower rates of smoking, stroke, congestive heart failure, and diabetes. Major postoperative complications accumulated progressively: stroke (11.6%), myocardial infarction (14.1%), deep vein thrombosis (6.6%), pulmonary embolism (6.1%), and contralateral limb amputation (54.2%) by 11 years. All-cause mortality reached 19.9% at 1 year and 34.6% at 20 years. Conclusions: AKA represents a sentinel event signaling advanced systemic vascular disease and high long-term morbidity and mortality. TriNetX data reveal substantial cerebrovascular, cardiovascular, and contralateral limb complications exceeding prior reports. These findings support multidisciplinary postamputation pathways emphasizing cardiovascular risk reduction, thromboembolic prophylaxis, wound management, and proactive contralateral limb surveillance to improve survival and quality of life.