Background: The prevalence of lower extremity artery disease (LEAD) is increasing worldwide in both sexes. Alone in Europe, over 40 million people are affected and sex as a risk factor for incidence and progression is a current matter of debate.

Purpose: The database provided by the AOK (Allgemeine Ortskrankenkasse) included routine data of an unselected "real-world" cohort with an in-patient treatment for LEAD with intermittent claudication (IC; Rutherford grade 1-3) between 01.01.2014 – 31.12.2015. We analysed risk profiles, therapeutic approach and its impact on the progression to chronic limb threatening ischemia (CLTI) and death including a pre pahase of two years before index and a follow-up up to five years.

Results: Our dataset comprised 42,197 patients with IC, thereof one third female (32.4% female vs. 67.6% male), being 6 years older compared to male LEAD patients (median age: 72.6 years female vs. 66.4 years male). Further, female patients had higher frequency of hypertension (90% vs. 87%), chronic kidney disease (29% vs. 26%), and obesity (27% vs. 25%), while male patients are more often diabetic (40% vs. 42%) or smoker (41% vs. 51%, all p<0.001) and had higher ratio of concomitant cardiovascular manifestation. During index hospitalisation, revascularisation applied to 83% LEAD patients while endovascular revascularisation was more common in female patients (66% female vs. 63% male) and vascular surgery was more frequently performed in male patients (18% female vs. 23% male, both p<0.001). At admission, female patients with IC had less often guideline-recommended medication (statins: 46% female vs. 50% male, p<0.001; platelet aggregation inhibitor: 30% female vs. 36% male, p<0.001; oral anticoagulation: 9% female vs 10% male, p=0.007). Also during two years of follow-up, male patients were supplied more frequently with statins (statins: 72% female vs. 75% male, p<0.001) and platelet aggregation inhibitor (74% female vs. 76% male, p<0.001). However, the rate of re-interventions were higher in male patients (33% female vs. 36% male; p<0.001) during two years after index. After adjustment for risk profiles, female sex was associated with increased overall survival (HR 0.76; 95%-CI 0.72-0.80) and CLTI-free survival which is a combined endpoint of CLTI (Rutherford stage 4-6 and/or amputation of the LL) and/or death (HR 0.89; 95%-CI 0.86-0.93).

Conclusion: Female patients with low stage LEAD are older, undersupplied with guideline-recommended medication and receive less often revascularising procedures of the LL compared to men. However, female patients have a lower risk for all-cause mortality and the combined endpoint CLTI and death during 5 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 patients with IC.

Figure 1: Kaplan-Meier curve for endpoints (A) overall-survival and (B) CLTI-free-survival during the study period (in years) displayed for female (red) vs. male (blue) patients with lower extremity artery disease at Rutherford stage 1-3.