Title: Investigation of Sex-Specific Discrepancies in Peri-operative Mortality and Morbidity following Elective Abdominal Aortic Aneurysm Repair: Are Sex-specific Pathways Needed to Provide Equality in Delivery of Care?
Funder: Department of Health and Social Care

Abstract: Research question Why do women experience higher mortality and complication rates following elective abdominal aortic aneurysm (AAA) repair? We will examine whether (potentially correctable) sex-specific differences in patient selection, anatomical complexity, preparation for and response to AAA surgery contribute to the disparity in outcomes.Background Operative mortality is observed to be higher in women than men for AAA repair. Differences remain following adjustment for age and co-morbidities, and the reasons for this are unknown.Sex-specific differences have been reported in the epidemiology and rupture risk of AAA. However, as the incidence of AAA is 5 times higher in men, the majority of evidence-based investigations, classification and care pathways have been tailored to them. This 'one-size-fits-all' approach may leave women neglected.We updated a meta-analysis of sex-specific 30-day mortality, with novel secondary analysis of risk factors and peri/post-operative complications, for elective AAA repair. This confirmed a significantly higher mortality risk for women: open repair (OAR, OR1.49 [95%CI1.38-.162]); endovascular repair (EVAR) (OR1.87 [95%CI1.57-2.23]), despite a lower incidence of major pre-operatively identified risk factors such as coronary artery disease (OR0.65 [95%CI0.48-0.87]) and diabetes (OR0.85 [95%CI0.75-0.97]). Peri-operatively, women were more likely to require transfusion (OR 2.18 [95%CI2.08-2.29]), experience arterial injury (OR3.02 [95%CI1.62-5.65]), suffer ischaemic complications (bowel (OR1.90 [95%CI1.42-2.53]), lower limb (OR2.11 [95%CI1.32-3.77]), suggesting potential differences in anatomical/operative complexity. Post-operatively, a higher rate of cardiac (OR1.20 [95%CI1.04-1.39], respiratory (OR1.58 [95%CI1.21-2.06]), and renal (OR1.45 [95%CI1.22-1.72]) complications, and longer hospital stay were observed, which might be due to differences in pre-operative optimisation or in response to surgical stress. In order to mitigate these sex-specific discrepancies, detailed investigation is required.Aims and objectives With the aim to identifying key correctible causes, to enable quality improvement and equitable provision of care, we will explore the hypotheses that increased mortality and complications in women undergoing elective AAA repair are due to sex-specific differences in: Recognition and management of pre-operative co-morbidities Anatomical complexity Selection for surgery Surgical stress responseMethods We will conduct:(1) A retrospective cohort study using national vascular registry (NVR) data to investigate differences in pre-operative status. Collaboration with NIHR-Health Informatics Collaborative will enable exploration of pre-operative preparation and identified significant risk factors in greater detail.(2) A retrospective evaluation of >1000 scans for sex-specific differences in AAA anatomy, and resultant association with peri-operative complications, with potential for expansion through collaboration with the UK-COMPASS study.(3) A discrete choice experiment to explore the role of patient sex as a variable on surgeon's selection for operative repair.(4) A prospective multi-centre cohort study, co-managed with PPI, to examine differences in the stress response to AAA surgery.Anticipated impact and dissemination Results will be disseminated, with the help of patients and charitable foundations, (through social media, publications and presentations,) to patients, clinicians, researchers and relevant societies, in order to stimulate awareness and further research. Identified key correctible causes will be translated into future prospective studies of novel sex-specific treatment pathways to improve outcomes for women undergoing AAA repair.

Lay abstract: Background The abdominal aorta is the main blood vessel supplying blood to the lower body. When a section of this vessel becomes swollen it is called an abdominal aortic aneurysm (AAA). If they grow too large, AAAs can burst, which can cause death. To prevent this, larger AAAs can be operated on beforehand, called 'elective repair'. This can be done with 'open surgery', (cutting open the tummy area,) or by 'endovascular surgery', (relining the vessel from inside).Worldwide, women are more likely than men to both die from elective AAA repair, and to suffer complications, even when we adjust for differences in fitness and age. The reason for this is unknown.Guidelines for the best treatment of AAAs have been based on what works for men, as they are more likely to develop an AAA. However, using these guidelines, women are more likely to die or suffer complications from AAA repair, or to be turned down for treatment. Women with AAAs are more likely to burst at a smaller size, are less likely to be offered 'endovascular surgery', and respond differently to the stress of surgery. This suggests that women might benefit from a different AAA treatment plan to men. More research is needed to work out the best way to do this.Aims The aim of this project is to explore why women are dying and suffering more complications from AAA repair than men and to identify causes we can correct.We will investigate four key areas. Whether women: have more medical issues and are less well looked after before surgery have AAAs with a shape which makes them more complicated to treat are selected differently for AAA repair respond differently to the stress of AAA repair.Methods (i)We will use large sets of data collected from patients treated in the UK to see if other medical issues and their treatments before AAA repair explain the increase in death and complications for women.(ii) We will look at over 1000 scans from the last 10 years to see if difference in the shape of AAAs in men and women are linked to more difficult AAA repair and worse outcomes for women.(iii) We will test surgeon's decision making in a 'discrete choice experiment', to see whether the sex of the patient affects the treatment they offer..(iv) We will carry out a study on men and women, who are set to undergo AAA repair. We will use fluid samples and heart monitoring to assess whether women experience higher stress before, during and after their operations. This may explain some of the differences in outcomes from AAA repair.Patient and Public InvolvementPatient and public involvement groups have recognised the topic as an area, which urgently needs research. They have advised on the design of the project and will help us to investigate the issues that are most important to patients and families. They will advise on the studies, help to interpret and share results, and help us to use the findings to create future research and quality improvement projects.DisseminationThe results will be shared with researchers, doctors and those who advise on how patients should be prepared for surgery, to increase awareness of differences in the treatment of men and women with AAAs. The results will also be shared with patients and relatives, to empower them to make educated decisions about their choice of treatment. From this work, we hope to improve the quality of patient care, to ensure that both men and women with AAA receive the best possible treatment, with better outcomes.

Research activity codes: 6.4 SURGERY;7.3 MANAGEMENT AND DECISION MAKING
Health categories: CARDIOVASCULAR