Age-Dependent Outcome of First-Line Endovascular and Surgical Revascularization Strategies in Chronic Limb-Threatening Ischemia

Abstract

Chronic limb-threatening ischemia (CLTI) has a high mortality and amputation risk even after revascularization. Owing to an aging population the incidence of peripheral arterial disease is rising. However, the current age distribution in patients with CLTI and the impact of age on outcomes remains unclear. For this reason we performed an age-dependent analysis of mortality, morbidity, and amputation-free survival after open surgical revascularization (OSR) and endovascular revascularization therapy (ERT) with identification of risk factors for mortality. Standardized mortality ratios (SMR) were calculated, comparing observed deaths in the study population to expected deaths based on age and gender specific mortality rates of the overall Dutch population. Patients revascularized for the first episode of CLTI between 2013 and 2018 were included in this multicenter retrospective cohort study. The cohort was divided into 2 treatment groups (OSR and ERT) who were each stratified in 3 age groups: early age group < 65 years (G1), middle age group 65-74 years (G2), and elderly age group ≥ 75 years (G3). During the study period 274 limbs (43.9%) were treated with OSR and 350 limbs (56.1%) with ERT. The young population (G1) is only a small part of the whole CLTI population, namely for OSR 22% and ERT 18%. The risk profile of the early age group was characterized by male gender and smoking, whereas the elderly age group was characterized by poor arterial runoff, tissue loss, hypertension, hypercholesterolemia, chronic kidney disease, history of heart disease, chronic obstructive pulmonary disease, and cerebrovascular disease. One year amputation rates were similar between the age groups. However, significantly higher one-year mortality rates were observed in patients ≥ 75 years in comparison to the low mortality rates in patients < 75 years (OSR: G3 19.8% vs. G2 7.1% and G1 6.7%, P = 0.006; ERT: G3 30.7% vs. G2 12.7% and G1 7.8%, P = 0.001). The SMR in this elderly group equaled 3.72 after OSR and 4.04 after ERT. Independent risk factors for mortality after OSR were age, hazard ratio (HR) 1.03 (95% confidence interval [CI] 1.01-1.06; P = 0.006), preoperative hemoglobin level (HR 0.79; 95% CI 0.67-0.92; P = 0.003), tissue loss (HR 1.85; 95% CI 1.22-2.79; P = 0.004), cardiac history (HR 1.56; 95% CI 1.06-2.30; P = 0.024), and development of postoperative delirium (HR 2.75; 95% CI 1.61-4.71; P < 0.001). After ERT we identified age, HR 1.06 (95% CI 1.04-1.08; P < 0.001); preoperative hemoglobin level, HR 0.75 (95% CI 0.65-0.87; P < 0.001); tissue loss, HR 1.71 (95% CI 1.15-2.53; P = 0.008); history of chronic obstructive pulmonary disease, HR 1.99 (95% CI 1.43-1.79; P < 0.001); history of cerebrovascular accident (CVA), HR 1.55 (95% CI 1.09-2.21; P = 0.015); the development of postoperative pneumonia, HR 2.27 (95% CI 1.24-4.16; P = 0.008); postoperative acute kidney injury (AKI), HR 2.42 (95% CI 1.29-4.54; P = 0.006); and postoperative CVA, HR 8.17 (95% CI 1.96-34.15; P = 0.004) as risk factors. The current CLTI population consists mostly of elderly patients and only a small part is younger than 65 years. This shift in the population is important because increasing age is associated with considerable higher one-year mortality rates regardless of the method of revascularization in patients with CLTI. The mortality rates in the elderly group are 3 to 4 times larger than expected in the general population. In relation to the high mortality of the elderly patient, we assume that interventions to prevent postoperative delirium and correct preoperative anemia may be warranted as they appear to be independent risk factors for mortality.