Conditional survival analysis and risk factors for mortality in patients with chronic limb-threatening ischemia

Overall survival (OS) for patients with chronic limb-threatening ischemia (CLTI) is notably poor, yet traditional survival estimates made at diagnosis fail to account for changes in survival probability over time. Conditional survival (CS) provides a dynamic measure of survival, indicating the likelihood that a patient will survive an additional period, given that they have already lived a certain number of years. Our study aimed to apply this model, commonly used in oncology, to evaluate how clinical presentation, comorbidities, and management impact continued survival in patients with CLTI. Specifically, we sought to determine: (1) conditional survival at 1, 3, and 5 years for patients with CLTI; and (2) the risk factors associated with survival outcomes.

Data were retrospectively collected from our institutional database, identifying patients with CLTI through International Classification of Diseases-9 and -10 codes between 2007 and 2017. Kaplan-Meier survival analysis was conducted from the time of diagnosis. Baseline characteristics from medical records were assessed for their impact on OS. Univariate and multivariate Cox regression models were used to identify factors associated with mortality.

A total of 3865 patients with a CLTI diagnosis were included. The 5-year overall survival rate was 29.5%. Conditional survival analysis revealed that, among patients who survived to 2 years post-diagnosis, the probability of surviving one additional year (to year 3) was 83%. Similarly, patients surviving to 3 years had an 82% likelihood of surviving to year 4. Several factors were significantly associated with increased mortality in multivariate analysis, including CLTI with ulceration, the need for hemodialysis, intensive care unit admission at diagnosis, ischemic heart disease, nursing facility residency, and a history of stroke. Reduced mortality was associated with clopidogrel use and an outpatient diagnosis. Aspirin use was linked to reduced mortality in univariate but not multivariate analysis. Within 1 year of diagnosis, both major amputation and endovascular revascularization were significant for mortality in univariate analysis. Subsequent multivariate analysis showed that major amputation within 1 year was significant for mortality at years 0, 1, and 3.

Conditional survival improves in patients with CLTI who survive beyond the first year post-diagnosis, yet 5-year mortality remains high. This finding highlights the substantial early mortality risk in patients with CLTI but also indicates that surviving the first year significantly improves subsequent survival odds. Several factors contribute to early mortality risk in CLTI, many of which are modifiable, underscoring the importance of targeted interventions in this high-risk population.