Editor's Choice - Impact of Sex on the Outcomes of Patients Undergoing Repair for Lower Extremity Peripheral Arterial Disease in France.

Lower extremity peripheral artery disease (PAD) affects more than 236 million people worldwide and although the disease is associated with high morbidity and mortality risk, it remains underdiagnosed and undertreated.1Aboyans V. Ricco J.B. Bartelink M.E.L. Bjorck M. Brodmann M. Cohnert T. et al.Editor's Choice – 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS).Eur J Vasc Endovasc Surg. 2018; 55: 305-368Abstract Full Text Full Text PDF PubMed Scopus (557) Google Scholar This especially affects the subgroup of women where clinical diagnosis is often delayed due to asymptomatic or atypical clinical presentation.2Pabon M. Cheng S. Altin S.E. Sethi S.S. Nelson M.D. Moreau K.L. et al.Sex differences in peripheral artery disease.Circ Res. 2022; 130: 496-511Crossref PubMed Scopus (19) Google Scholar Women have been underrepresented in medical cardiovascular research and although efforts have been made over the past decades, there is still a gap to fill to improve quality and equity of care.2Pabon M. Cheng S. Altin S.E. Sethi S.S. Nelson M.D. Moreau K.L. et al.Sex differences in peripheral artery disease.Circ Res. 2022; 130: 496-511Crossref PubMed Scopus (19) Google Scholar,3Behrendt C.A. Sigvant B. Kuchenbecker J. Grima M.J. Schermerhorn M. Thomson I.A. et al.Editor's Choice – International variations and sex disparities in the treatment of peripheral arterial occlusive disease: a report from VASCUNET and the International Consortium of Vascular Registries.Eur J Vasc Endovasc Surg. 2020; 60: 873-880Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar The impact of sex on outcomes of patients with PAD is still poorly understood, and there is an urgent need to report sex specific analysis to better understand sex differences and provide evidence to build sex specific guidelines further. This 10 year retrospective multicentre nationwide study aimed to investigate the impact of sex on outcomes of patients undergoing treatment for PAD in France. Data were extracted from the French National Health Insurance Information System, which compiles standardised data on all patients hospitalised in France. Inclusion criteria were all patients admitted for any index invasive revascularisation of PAD in a public or private hospital between 1 January 2013 and 30 June 2022. Patients who had secondary interventions were excluded. Data collected at inclusion were age, sex, clinical presentation of PAD, and comorbidities defined according to the World Health Organisation International Classification of Diseases 10 and to the Common Classification of Medical Acts. The OAC3-PAD bleeding risk score and major bleeding were defined based on previous publications.4Behrendt C.A. Kreutzburg T. Nordanstig J. Twine C.P. Marschall U. Kakkos S. et al.The OAC3-PAD risk score predicts major bleeding events one year after hospitalisation for peripheral artery disease.Eur J Vasc Endovasc Surg. 2022; 63: 503-510Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar For follow up, an alphanumerical anonymous identifier was used in the French National Insurance Information System to identify any re-hospitalisations in longitudinally linked data for each patient. Outcomes investigated were major bleeding, amputation, and overall mortality rate within one year follow up. A total of 247 981 patients who underwent index revascularisation of PAD were included in the analysis, among whom 183 903 (74.2%) patients had endovascular interventions. The mean age was 71 ± 12 years and 171 430 (69.1%) were men. Women were significantly older than men at the time of selection for treatment (76 vs. 68 years, p < .001) and more often had gangrene (30.9% vs. 17.9%, p < .001). The Charlson comorbidity index was significantly higher in men (8.8 vs. 4.4, p < .001) while women had a higher OAC3-PAD bleeding score (3.5 vs. 2.5, p < .001). In univariable analysis, follow up at one year showed that overall mortality was higher in women (7.7% vs. 5.9%, p < .001); amputation rates were lower (3.7 vs. 3.9%, p = .005), and major bleeding occurred similarly (5.5% vs. 5.5%, p = .80). Applying a logistic regression model, male sex was significantly associated with major bleeding, amputation, and death within one year following the index treatment after adjustment for age, Charlson comorbidity index, OAC3-PAD bleeding score, presence of gangrene, and revascularisation procedure (Table 1).Table 1Association between male sex and one year amputation, mortality, and major bleeding after adjustment for age, Charlson comorbidity index, OAC3-PAD bleeding score, presence of gangrene, and revascularisation procedure (endovascular or open intervention).One year amputation rateOne year mortality rateOne year major bleeding rateAdjusted OR, male sex (ref. female sex)1.201.131.1195% CI1.15 – 1.261.09 – 1.171.06 – 1.15p value<.001<.001<.001CI = confidence interval; OR = odds ratio; ref. = reference. Open table in a new tab CI = confidence interval; OR = odds ratio; ref. = reference. This nationwide analysis showed that women were older and more often had gangrene when they were selected for revascularisation. These results suggest that women are diagnosed and or treated at a more advanced stage than men. Historically, women with PAD have undergone revascularisation less frequently than their male counterparts.2Pabon M. Cheng S. Altin S.E. Sethi S.S. Nelson M.D. Moreau K.L. et al.Sex differences in peripheral artery disease.Circ Res. 2022; 130: 496-511Crossref PubMed Scopus (19) Google Scholar Although male sex is no longer an independent predictor for revascularisation, the current literature indicates that women with PAD still have less frequent use of guideline directed pharmacological treatment than men.2Pabon M. Cheng S. Altin S.E. Sethi S.S. Nelson M.D. Moreau K.L. et al.Sex differences in peripheral artery disease.Circ Res. 2022; 130: 496-511Crossref PubMed Scopus (19) Google Scholar The present study showed that after multivariable analysis, female sex was not associated with worse outcomes after revascularisation, and interestingly male sex was even identified as an independent risk factor of major bleeding, amputation, and death within one year following the index treatment. Heterogeneous results were reported in the literature.2Pabon M. Cheng S. Altin S.E. Sethi S.S. Nelson M.D. Moreau K.L. et al.Sex differences in peripheral artery disease.Circ Res. 2022; 130: 496-511Crossref PubMed Scopus (19) Google Scholar,5Lee M.H. Li P.Y. Li B. Shakespeare A. Samarasinghe Y. Feridooni T. et al.A systematic review and meta-analysis of sex- and gender-based differences in presentation severity and outcomes in adults undergoing major vascular surgery.J Vasc Surg. 2022; 76: 581-594Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar A meta-analysis including 2 394 143 patients who underwent open or endovascular peripheral revascularisation procedures found that the overall mortality rate was higher in women than in men (relative risk 1.14; 95% confidence interval 1.05 – 1.23).5Lee M.H. Li P.Y. Li B. Shakespeare A. Samarasinghe Y. Feridooni T. et al.A systematic review and meta-analysis of sex- and gender-based differences in presentation severity and outcomes in adults undergoing major vascular surgery.J Vasc Surg. 2022; 76: 581-594Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Another study including 50 051 patients who underwent percutaneous endovascular revascularisation for symptomatic PAD from the second largest German health insurance fund found that female patients had a lower overall mortality rate, and fewer cardiovascular events, amputation, or death within five years following surgery.6Heidemann F. Kuchenbecker J. Peters F. Kotov A. Marschall U. L’Hoest H. et al.A health insurance claims analysis on the effect of female sex on long-term outcomes after peripheral endovascular interventions for symptomatic peripheral arterial occlusive disease.J Vasc Surg. 2021; 74: 780-787Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar These results bring new insights and generate interesting hypotheses in the field and further underline the complex impact of sex on PAD epidemiology and management. It highlights the need to work towards reporting sex specific outcomes to improve patient care and contribute to precision medicine in vascular diseases. This retrospective observational study based on an electronic administrative database study may have some limitations as the results depend on the quality of the coding system. Detailed information regarding pharmacological treatment of PAD was not available. Events that may have occurred in the absence of hospitalisation could not be recorded in the database. Nevertheless, the French National Information System uses a standardised classification and the quality of data are audited by experts. Also, it can be assumed that most major outcomes such as amputation or major bleeding may have led to hospitalisation of patients, thus limiting bias due to loss of follow up. None. This work has been supported by the French government through the National Research Agency (ANR) with the reference number ANR-22-CE45-0023-01 and through the 3IA Côte d’Azur Investments in the Future project with the reference number ANR-19-P3IA-002. C.A.B. received national funds from the German Federal Joint Committee (grant numbers 01VSF18035 and 01VSF16008).