Contemporary Treatment and Outcome of Patients with Ischaemic Lower Limb Amputation: A Focus on Sex Differences

Abstract

Objective: Chronic limb threatening ischaemia (CLTI) has a devastating prognosis with high rates of lower limb amputation (LLA) and deaths. This is an illustration of contemporary management and the long term fate of patients after ischaemic LLA, particularly with respect to sex, using real world data.

Methods: This was a multisectoral cross sectional and longitudinal analysis of health claims data from the largest German health insurance database (AOK). Data of 39 796 propensity score matched patients hospitalised for ischaemic LLA between 2010 and 2018 were analysed for cardiovascular comorbidities, treatment, and for subsequent cardiovascular and limb events, with a distinct focus on sex. Matching was performed, to ensure that the rate of major amputations and the age distribution were equal in both groups (in both sexes). An observation period of two years before index and a follow up (FU) period until 2019 were included.

Results: Before index amputation, 68% of patients had received any kind of peripheral revascularisation. The use of statins (37.0% vs. 42.6%) and antithrombotic substances (54.9% vs. 61.8%) was lower in women than in men (p < .001). During two year FU, cardiovascular and limb events occurred among women and men as follows: limb re-amputation (26.7% vs. 31.2%), myocardial infarction (10.9% vs. 14.5%), stroke (20.8% vs. 20.7%), and death from any cause (51.0% vs. 53.3%, p < .001 except for stroke). After adjustment for cardiovascular comorbidities and vascular procedures, female sex was associated with a higher probability of death (HR 1.04, 95% CI 1.04 - 1.04).

Conclusion: Patients undergoing ischaemic LLA still have a poor prognosis marked by high rates of recurrent cardiovascular and limb events resulting in a > 50% mortality rate within two years. The continuous lack of guideline recommended therapies, particularly in women, may be associated with the persisting poor outcome, necessitating urgent further investigation.

Keywords: Amputation; Chronic limb threatening ischaemia; Lower extremity artery disease; Outcome research; Overall survival; Sex differences.