Background: The prevalence of chronic limb threatening ischemia (CLTI) is increasing worldwide. Patients with CLTI have a poor prognosis in terms of lower limb (LL) amputation and mortality. For a better understanding of sex related differences in treatment and outcome, we analyzed health claims data of a public German insurance.

Methods: The database provided by the AOK (Allgemeine Ortskrankenkasse) includedroutine data of an unselected "real-world" cohort. All patients with in-patient treatment for lower extremity artery disease (LEAD) at Rutherford stage (RF) 4-6 (CLTI) between 01.01.2010 – 31.12.2017 were included. We analyzed the risk profile, therapeutic approach and its impact on amputation of the LL and death including a two-year baseline phase before index and a follow-up until the end of 2018.

Results: In our cohort of 199,953 hospitalized CLTI patients, women represented the minority (43% women vs. 57% men; p<0.001) and were older (median 81.4 years vs. 73.8 years; p<0.001). Furthermore, women were more often diagnosed with hypertension, atrial fibrillation (AF), chronic heart failure (CHF) and chronic kidney disease (CKD), while male patients suffered more frequently from diabetes mellitus, dyslipidaemia, smoking, cerebrovascular disease (CVD) and chronic coronary syndrome (CCS). In contrast, a matched cohort (age and RF stages) showed higher prevalence of AF, CHF and CKD in males (all p<0.001). The prescription rate of guideline-recommended drugs like statins (35% vs. 43%) and antithrombotic therapy (48% vs. 53%; both p<0.001) was lower in female patients during baseline. Furthermore, women underwent less frequently vascular procedure (diagnostic angiographies: 67% vs. 70%, revascularization 61% vs. 65%; both p<0.001) during index-hospitalisation. The descriptive mortality rate by Kaplan Meier estimates showed higher risk of death in women after 5 years (unmatched cohort: female risk ratio 1.17; 95%CI 1.15-1.18; p<0.001), while no differences between the sexes were observed for the combined endpoint death and amputation of the LL. After Cox regression analysis adjusted for age and cardiovascular comorbidities, female sex was associated with increased overall-survival (HR 0.95; 95%CI 0.94-0.96) and amputation-free-survival (HR 0.84; 95%CI 0.83-0.85; both p<0.001).

Conclusion: Female patients with CLTI were older, received less often vascular procedures and were undersupplied with guideline-recommended drug therapies. However, female patients had a lower risk for all-cause mortality and the combined endpoint of amputation of the LL and/or death during 9 years follow-up. Further analyses with focus on sex-related differences on therapy and outcome are needed to correspond to the individual needs of male and female LEAD patients.