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Editor's Choice – Systematic Review and Meta-Analysis of Sex Specific Differences in Adverse Events After Open and Endovascular Intact Abdominal Aortic Aneurysm Repair: Consistently Worse Outcomes for Women

Open ArchivePublished:July 28, 2021DOI:https://doi.org/10.1016/j.ejvs.2021.05.029

      Objective

      Previously, reports have shown that women experience a higher mortality rate than men after elective open (OAR) and endovascular (EVAR) repair of abdominal aortic aneurysm (AAA). With recent improvements in overall AAA repair outcomes, this study aimed to identify whether sex specific disparity has been ameliorated by modern practice, and to define sex specific differences in peri- and post-operative complications and pre-operative status; factors which may contribute to poor outcome.

      Methods

      This was a systematic review, meta-analysis, and meta-regression of sex specific differences in 30 day mortality and complications conducted according to PRISMA guidance (Prospero registration CRD42020176398). Papers with ≥ 50 women, reporting sex specific outcomes, following intact primary AAA repair, from 2000 to 2020 worldwide were included; with separate analyses for EVAR and OAR. Data sources were Medline, Embase, and CENTRAL databases 2005 – 2020 searched using ProQuest Dialog.

      Results

      Twenty-six studies (371 215 men, 65 465 women) were included. Meta-analysis and meta-regression indicated that sex specific odds ratios (ORs) for 30 day mortality were unchanged from 2000 to 2020. Mortality risk was higher in women for OAR and more so for EVAR (OR [95% CI] 1.49 [1.37 – 1.61]; 1.86 [1.59 – 2.17], respectively) and this remained following multivariable risk adjustment. Transfusion, pulmonary complications, and bowel ischaemia were more common in women after OAR and EVAR (OAR: ORs 1.81 [1.60 – 2.04], 1.40 [1.28 – 1.53], 1.54 [1.36 – 1.75]; EVAR: ORs 2.18 [2.08 – 2.29] 1.44 [1.17 – 1.77], 1.99 [1.51 – 2.62], respectively). Arterial injury, limb ischaemia, renal and cardiac complications were more common in women after EVAR (ORs 3.02 [1.62 – 5.65], 2.13 [1.48 – 3.06], 1.46 [1.22 – 1.72] and 1.19 [1.03 – 1.37], respectively); the latter was associated with greater mortality risk on meta-regression.

      Conclusion

      Increased mortality risk for women following AAA repair remains. Women had a higher incidence of transfusion, pulmonary and bowel complications after EVAR and OAR. Higher mortality risk ratios for EVAR may result from cardiac complications, additional arterial injury, and embolisation, leading to renal and limb ischaemia. These findings indicate possible causes for observed outcome disparities and targets for quality improvement.

      Keywords

      This study demonstrates that the risk of worse outcomes in women (vs. men) after elective abdominal aortic aneurysm repair has not ameliorated with time and the risk ratio for mortality is higher for EVAR than open repair. Sex specific differences varied with type of repair, allowing insight into the increased mortality risk differential for EVAR. Better pre-operative optimisation might reduce the higher risk of systemic complications in women. Arterial injury, renal, and other ischaemic complications (limb and bowel ischaemia), which probably contribute to mortality, are higher in women, especially after EVAR, and may be avoidable with strategic planning.

      Introduction

      Higher operative mortality for women (vs. men) undergoing open (OAR) or endovascular (EVAR) abdominal aortic aneurysm (AAA) repair has been reported worldwide.
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      Editor’s Choice: Assessment of international outcomes of intact abdominal aortic aneurysm repair over 9 years.
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      Sex differences in mortality after abdominal aortic aneurysm repair in the UK.
      This discrepancy remains following multivariable risk factor adjustment, indicating that differences in age or pre-operatively identified comorbid status do not adequately explain the increase in mortality risk for women.
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      Editor’s Choice: Assessment of international outcomes of intact abdominal aortic aneurysm repair over 9 years.
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      Sex differences in mortality after abdominal aortic aneurysm repair in the UK.
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      Women derive less benefit from elective endovascular aneurysm repair than men.
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      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
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      Salient analysis of key sex specific differences is hindered by substantial under representation of women in major trials, disparate reporting of comorbidities and outcomes, and frequent pooled reporting of intact and ruptured AAA repair.
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      Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.
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      Further investigation, and a greater understanding of key contributory factors, such as sex specific differences in peri- and post-operative complications, is needed.
      Additionally, over the last 20 years, improvement in pre-operative optimisation, patient selection, and multidisciplinary supportive care have improved outcomes dramatically for AAA repair.
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      Advances in available devices and techniques for minimally invasive endovascular repair have also considerably reduced peri-operative mortality, can be performed under local anaesthesia, and reduce recovery time.
      • Powell J.T.
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      Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.
      However, while these advances are advantageous to both sexes, it is unclear whether improvements have been conferred equally, with some reports suggesting a widening of the mortality risk differential.
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      Systematic review and meta-analysis of sex differences in outcomes after endovascular aneurysm repair for infrarenal abdominal aortic aneurysm.
      A recent meta-analysis, conducted by Liu et al., explored sex specific differences after EVAR for infrarenal AAA, demonstrating an increased risk of mortality, limb ischaemia, cardiac, and renal complications for women.
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      • Zhao J.
      • Chen X.
      • Wang J.
      • Ma Y.
      • et al.
      Systematic review and meta-analysis of sex differences in outcomes after endovascular aneurysm repair for infrarenal abdominal aortic aneurysm.
      However, because of the inclusion of patient cases from an outdated era, prior to key advances in endovascular techniques, low profile devices, and anaesthesia and intensive care strategies, these results may not be reflective of modern practice.
      • Powell J.T.
      • Sweeting M.J.
      • Ulug P.
      • Blankensteijn J.D.
      • Lederle F.A.
      • Becquemin J.
      Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.
      ,
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      ,
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      • Golden M.A.
      • et al.
      Midterm pivotal trial results of the Talent Low Profile System for repair of abdominal aortic aneurysm: analysis of complicated versus uncomplicated aortic necks.
      Indeed, more recent studies have reported that despite increased peri-procedural complications for women, there is no difference in survival following EVAR.
      • Chung C.
      • Tadros R.
      • Torres M.
      • Malik R.
      • Ellozy S.
      • Faries P.
      • et al.
      From the Midwestern Vascular Surgical Society: Evolution of gender-related differences in outcomes from two decades of endovascular aneurysm repair.
      Additionally, without comparison with OAR, it was not possible to assess whether differences in the complication risks reported by Liu et al. were a result of disadvantages specifically associated with EVAR affecting women disproportionately.
      • Liu Y.
      • Yang Y.
      • Zhao J.
      • Chen X.
      • Wang J.
      • Ma Y.
      • et al.
      Systematic review and meta-analysis of sex differences in outcomes after endovascular aneurysm repair for infrarenal abdominal aortic aneurysm.
      This study aimed to explore the hypothesis that, in modern practice, women continue to be at greater risk of death and post-operative complications from elective AAA repair (with an increased risk differential for EVAR over OAR), as well as to examine potential pre-, peri-, and post-operative causes for this disparity. This was performed using a systematic review, meta-analysis, and meta-regression, examining sex specific differences in mortality, post-operative complications, and pre-operative status, for both OAR and EVAR for intact AAA.

      Methods

      The protocol for this systematic review and meta-analysis was registered with the International Prospective Register of Systematic Reviews (PROSPERO, CRD42020176398). The study has been conducted and reported in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines (Supplementary Table S1).
      • Deeks J.J.
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      • Altman D.G.
      Chapter 10: Analysing data and undertaking meta-analyses.
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      • Berlin J.A.
      • Morton S.C.
      • Olkin I.
      • Williamson G.D.
      • Rennie D.
      • et al.
      Meta-analysis of observational studies.
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      • Prisma T.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

      Search strategy, selection, and data extraction

      An update of a comprehensive search strategy ProQuest Dialog was created for MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) using a combination of controlled vocabulary (MeSH or EMTREE) terms and free text terms, with a final search data of 31 January 2021.
      • Ulug P.
      • Sweeting M.J.
      • Thompson S.G.
      • Powell J.T.
      Morphological suitability for endovascular repair, non-intervention rates, and operative mortality in women and men assessed for intact abdominal aortic aneurysm repair: systematic reviews with meta-analysis.
      Papers with ≥ 50 women, reporting sex specific outcomes, following intact, primary AAA repair, with separate reporting for EVAR and OAR, from 2000 to 2020 worldwide were included. The detailed search strategy, inclusion and exclusion criteria are given in Table 1. The criterion of ≥ 50 women was established by a senior statistician, for an earlier set of reviews, to reduce bias and the confidence intervals on the odds ratios (ORs) (which relate to both the number of events and the size of the study).
      • Ulug P.
      • Sweeting M.J.
      • Thompson S.G.
      • Powell J.T.
      Morphological suitability for endovascular repair, non-intervention rates, and operative mortality in women and men assessed for intact abdominal aortic aneurysm repair: systematic reviews with meta-analysis.
      Manual searches of further information sources, such as the references from relevant published studies or reviews, conference abstracts, and supplementary notes, were also conducted. If necessary, authors were contacted to provide clarification or identify additional data.
      • Ultee K.H.J.
      • Zettervall S.L.
      • Soden P.A.
      • Darling J.
      • Bertges D.J.
      • Verhagen H.J.M.
      • et al.
      Incidence of and risk factors for bowel ischemia after abdominal aortic aneurysm repair.
      • Gurakar M.
      • Locham S.
      • Alshaikh H.N.
      Risk factors and outcomes for bowel ischemia after open and endovascular abdominal aortic aneurysm repair.
      • Behrendt C.
      • Kreutzburg T.
      • Kuchenbecker J.
      • Panuccio G.
      • Dankhoff M.
      • Spanos K.
      • et al.
      Female sex and outcomes after endovascular aneurysm repair for abdominal aortic aneurysm: a propensity score matched cohort analysis.
      Potentially eligible reports were assessed by two independent reviewers, with discrepancies resolved by a third author and pre-specified data extracted (Supplementary Text S2). Publication quality and risk of bias was assessed using the Newcastle Ottawa Scale.

      Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for Assessing The Quality Of Nonrandomised Studies In Meta-Analyses. Ottawa Hospital Research Institute. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp [Accessed 3 Feb 2021].

      Table 1Inclusion and exclusion criteria and search strategy
      Search was done using the following terms: MESH.EXACT.EXPLODE "Aortic Aneurysm, Abdominal") OR (abdominal aort∗) AND aneurysm∗); MESH.EXACT("Blood Vessel Prosthesis"); MESH.EXACT("Blood Vessel Prosthesis Implantation"); MESH.EXACT("Aortic Aneurysm, Abdominal -- surgery")); MESH.EXACT("Aortic Aneurysm, Abdominal -- mortality"); MESH.EXACT("Aortic Aneurysm, Abdominal -- complications"); MESH.EXACT("Hospital Mortality"); MESH.EXACT("Minimally Invasive Surgical Procedures -- mortality"); MESH.EXACT("Vascular Surgical Procedures -- mortality"); MESH.EXACT.EXPLODE("Vascular Surgical Procedures : E.04.100.814 -- adverse effects"); mortality; MESH.EXACT.EXPLODE("Treatment Outcome"); EMB.EXACT.EXPLODE("abdominal aorta aneurysm"); (ab (abdominal aort∗) AND aneurysm); EMB.EXACT.EXPLODE("blood vessel prosthesis"); EMB.EXACT("aorta graft"); EMB.EXACT("blood vessel transplantation")); EMB.EXACT("endovascular aneurysm repair"); EMB.EXACT.EXPLODE("aortic aneurysm endovascular graft"); EMB.EXACT.EXPLODE("endovascular surgery")); EMB.EXACT("cardiovascular mortality"); EMB.EXACT.EXPLODE("surgical mortality"); EMB.EXACT.EXPLODE("mortality"); EMB.EXACT("treatment outcome"); repair; endovascular surgery; open surgery; mortality.
      for studies reporting sex specific outcomes after repair of abdominal aortic aneurysm (AAA)
      Inclusion criteriaExclusion criteria
      Operation date year 2000 or laterInclusion of AAA repair before 2000
      Age ≥ 55 yStudies of selected subgroups, thoracic aortic disease, or syndromic pathologies (e.g., Marfan syndrome)
      Clinical studies of AAA repairs including ≥ 50 womenReview articles, editorials, case reports, biomarker, pathobiology, and animal studies
      Separate reporting of open repair and endovascular repairCombined reporting of AAA outcomes (open and endovascular and/or other vascular and/or other surgical outcomes)
      Separate reporting of outcomes from intact AAA casesCombined reporting of outcomes from intact and ruptured AAA cases
      Studies including patients with infrarenal, juxtarenal, pararenal, or suprarenal AAAStudies of thoraco-abdominal and isolated iliac aneurysms
      Studies including endovascular aneurysm repair, branched, chimney, and fenestrated endograftsStudies of experimental technologies including Nellix and flow modulating stents
      For studies reporting duplicated data, the most recent or most comprehensive publication to be indexedSignificant attrition or insufficient data quality to enable data synthesis (e.g., reporting of hazard ratios alone)
      English language, major European languageDuplicated data (including abstracts and online ahead of print articles, patient series later updated, etc.)
      Not in English or major European language
      Search was done using the following terms: MESH.EXACT.EXPLODE "Aortic Aneurysm, Abdominal") OR (abdominal aort∗) AND aneurysm∗); MESH.EXACT("Blood Vessel Prosthesis"); MESH.EXACT("Blood Vessel Prosthesis Implantation"); MESH.EXACT("Aortic Aneurysm, Abdominal -- surgery")); MESH.EXACT("Aortic Aneurysm, Abdominal -- mortality"); MESH.EXACT("Aortic Aneurysm, Abdominal -- complications"); MESH.EXACT("Hospital Mortality"); MESH.EXACT("Minimally Invasive Surgical Procedures -- mortality"); MESH.EXACT("Vascular Surgical Procedures -- mortality"); MESH.EXACT.EXPLODE("Vascular Surgical Procedures : E.04.100.814 -- adverse effects"); mortality; MESH.EXACT.EXPLODE("Treatment Outcome"); EMB.EXACT.EXPLODE("abdominal aorta aneurysm"); (ab (abdominal aort∗) AND aneurysm); EMB.EXACT.EXPLODE("blood vessel prosthesis"); EMB.EXACT("aorta graft"); EMB.EXACT("blood vessel transplantation")); EMB.EXACT("endovascular aneurysm repair"); EMB.EXACT.EXPLODE("aortic aneurysm endovascular graft"); EMB.EXACT.EXPLODE("endovascular surgery")); EMB.EXACT("cardiovascular mortality"); EMB.EXACT.EXPLODE("surgical mortality"); EMB.EXACT.EXPLODE("mortality"); EMB.EXACT("treatment outcome"); repair; endovascular surgery; open surgery; mortality.

      Statistical analysis

      The methodology for statistical analysis was conducted in accordance with the Cochrane Handbook for Systematic Reviews, using RevMan 5.3 software and RStudio.
      RStudio Team
      RStudio: Integrated Development Environment for R. RStudio, PBC.
      ,
      Standard approximation methodology was used for conversion of non-parametric data to mean and standard deviation to enable cumulative analysis.
      • Wang W.
      • Liu J.
      • Tong T.
      Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range.
      In the absence of significant heterogeneity of study design and methodology (e.g. heterogeneity in definition of outcome variable), quantitative pooled meta-analyses of these data were conducted using the Mantel-Haenszel (dichotomous data), inverse variance (continuous data), or generic inverse variance (risk adjusted mortality ORs) method with a random effects model.
      • Wang W.
      • Liu J.
      • Tong T.
      Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range.
      Where sufficient data were identified (at least eight studies), meta-regression analyses were conducted to examine aggregate (study level) effects of significant covariates (e.g. midpoint of study, difference in age, and log odds of significant complications), on between study heterogeneity for log odds of operative mortality. A mixed effects model was performed, with studies weighted by a combination of the inverse of within study variance and the residual heterogeneity.
      • Harrer M.
      • Cuijpers P.
      • Furukawa T.A.
      • Ebert D.D.
      Doing Meta-Analysis in R. A Hands on Guide.
      For each meta-regression, the change in outcome per unit increase in covariable (βi, slope co-efficient (se, standard error)), the strength of association (p value), and the residual heterogeneity (tau2) are reported. A p value of < .050 was considered to be statistically significant. Heterogeneity was assessed using a chi square test and the I2 statistic, and publication bias was assessed using funnel plots, Egger’s test and Duval and Tweedie’s trim and fill procedure.
      • Wang W.
      • Liu J.
      • Tong T.
      Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range.
      ,
      • Duval S.
      • Tweedie R.
      Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis.
      Sensitivity analyses were undertaken to evaluate the stability of results (Supplementary Text S2).

      Results

      Study selection

      A total of 26 studies were eligible for inclusion. All studies were retrospective (in one case a retrospective analysis of data from prospective randomised controlled trials
      • Powell J.T.
      • Sweeting M.J.
      • Ulug P.
      • Blankensteijn J.D.
      • Lederle F.A.
      • Becquemin J.
      Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.
      ), 18 reported OAR and 25 reported EVAR, with a total of 371 215 men and 65 465 women (Fig. 1, Table 2). All studies had a low to moderate risk of bias on the Newcastle Ottawa scale (Table 1, Supplementary Fig. S3). For each reported variable, studies and supplementary data were examined to establish sufficient consistency in definitions to enable quantitative synthesis of data (Supplementary Tables S4 and S5).
      Figure 1
      Figure 1Preferred reporting items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram for search for studies reporting sex specific outcomes after open or endovascular (EVAR) repair of abdominal aortic aneurysm.
      Table 2Summary of included studies reporting sex specific outcomes after open aortic repair (OAR) or endovascular aneurysm repair (EVAR) of abdominal aortic aneurysm (AAA)
      StudyData sourceStudy periodOAR in men / womenEVAR in men / womenNO scoreReported variables
      Reported outcomes: Mortality: 1a, 30 d; 1b, in hospital; 1c long term. Peri/post-operative complications: 2a, blood transfusion, 2b, arterial injury, 2c, limb ischaemia, 2d, bowel ischaemia, 2e, cardiac, 2f, respiratory, 2g, neurological and 2h, renal complications, 2i, re-intervention and 2j, endoleaks. Duration of treatment: 3a operative time, 3b length of intensive care and 3c hospital stay. Pre-operative comorbidities and risk factors: 4a cardiovascular, 4b, respiratory, 4c, renal, 4d, diabetes, 4e, peripheral vascular disease, 4f, smoker, 4g, comorbidity score.
      nAge–yAAA diameter–mmnAge – yAAA diameter–mm
      UK
       Desai 2016
      • Desai M.
      • Choke E.
      • Sayers R.D.
      • Nath M.
      • Bown M.J.
      Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men.
      HES/ONS (IRAAA)2002–2013 (EVAR: 2006–13)26 295 / 4 79572 ± 8 /74 ± 814 741 / 2 03675 ± 7 /77 ± 881a,c, 2e–h, 4a-e,g
       Lowry 2016
      • Lowry D.
      • Singh J.
      • Mytton J.
      • Tiwari A.
      Sex-related outcome inequalities in endovascular aneurysm repair.
      HES/ONS (IRAAA)2006–201518 215 / 2 30476 (70–80) /78 (74–82)71a,c, 3c, 4c–e,g
       Sidloff 2017
      • Sidloff D.A.
      • Saratzis A.
      • Sweeting M.J.
      • Michaels J.
      • Powell J.T.
      • Thompson S.G.
      • et al.
      Sex differences in mortality after abdominal aortic aneurysm repair in the UK.
      NVR/HES (IRAAA)2010–20146 013 / 92272 ± 8 /74 ± 862 (57–72) /60 (56–67)10 452 / 1 30676 ± 8 /78 ± 760 (57–67) /59 (56–65)81b, 3b–c, 4a–d,f
      Germany
       Trenner 2018
      • Trenner M.
      • Kuehnl A.
      • Reutersberg B.
      • Salvermoser M.
      • Eckstein H.
      Nationwide analysis of risk factors for in-hospital mortality in patients undergoing abdominal aortic aneurysm repair.
      GFSO (IRAAA)2005–201333 815 / 5 20870 (65–75) /72 (67–78)40 777 / 4 83173 (68–78) /76 (71–82)81b, 2a 3c, 4a–e,g
       Trenner 2020
      • Trenner M.
      • Salvermoser M.
      • Busch A.
      • Reutersberg B.
      • Eckstein H.
      • Kuehnl A.
      Effect modification of sex and age for the outcome relationship in abdominal aortic aneurysm treatment: German Diagnosis Related Groups Statistics from 2005 to 2014.
      GFSO (IRAAA)2005–201435 876 / 5 61447 727 / 5 74991b, 3b, 4a–e
       Behrendt 2021
      • Behrendt C.
      • Kreutzburg T.
      • Kuchenbecker J.
      • Panuccio G.
      • Dankhoff M.
      • Spanos K.
      • et al.
      Female sex and outcomes after endovascular aneurysm repair for abdominal aortic aneurysm: a propensity score matched cohort analysis.
      DAK-G (IRAAA)2011–20173 136/ 77074 (8) / 75 (8)81b, 2a,c–f,h,i, 3c, 4d
      Holland
       Indrakusuma 2019
      • Indrakusuma R.
      • Jalalzadeh H.
      • Vahl A.C.
      • Koelemay M.J.W.
      • Balm R.
      Editor’s Choice - Sex related differences in peri-operative mortality after elective repair of an asymptomatic abdominal aortic aneurysm in the Netherlands: a retrospective analysis of 2013 to 2018.
      DSAA (IRAAA)2013–20182 056 / 50771 (66–76) /72 (67–77)7 581 / 1 15574 (68–79) /76 (66–76)81a, 4a,b
      USA
       Mehta 2012
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
      • Paty P.S.K.
      • et al.
      Women derive less benefit from elective endovascular aneurysm repair than men.
      Albany medical college (AAA)2002–2009579 / 20970 / 7362 / 581 248 / 34473 / 7556 / 5671a, 2a–f,h–j, 3c
       Schermerhorn 2012
      • Schermerhorn M.L.
      • Bensley R.P.
      • Giles K.A.
      • Hurks R.
      • O'Malley A.J.
      • Cotterill P.
      • et al.
      Changes in abdominal aortic aneurysm rupture and short term mortality 1995–2008.
      Medicare beneficiaries (AAA)20084 115 / 1 76415 590 / 3 65761a
       Lo 2013
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      VSGNE (IRAAA)2003–20111 117 / 41261 ± 14 /58 ± 121 660 / 40857 ± 11 /56 ± 1071a–c, 2a–f,h–j, 3a–c
       Ramanan 2013
      • Ramanan B.
      • Gupta P.K.
      • Sundaram A.
      • Gupta H.
      • Johanning J.M.
      • Lynch T.G.
      • et al.
      Development of a risk index for prediction of mortality after open aortic aneurysm repair.
      NSQIP (AAA)2007–20092 117 / 72881a
       Skibba 2015
      • Skibba A.A.
      • Evans J.R.
      • Hopkins S.P.
      • Yoon H.R.
      • Katras T.
      • Kalb H.
      • et al.
      Reconsidering gender relative to risk of rupture in the contemporary management of abdominal aortic aneurysms.
      Johnson City Medical Center (IRAAA)2000–2013371 / 104545 / 8351b
       Chung 2015
      • Chung C.
      • Tadros R.
      • Torres M.
      • Malik R.
      • Ellozy S.
      • Faries P.
      • et al.
      From the Midwestern Vascular Surgical Society: Evolution of gender-related differences in outcomes from two decades of endovascular aneurysm repair.
      Mount Sinai Hospital (IRAAA)2003–2012617 / 12175 ± 8 /78 ± 851a, 2a–c,f, 3c
       Ultee 2016
      • Ultee K.H.J.
      • Zettervall S.L.
      • Soden P.A.
      • Darling J.
      • Bertges D.J.
      • Verhagen H.J.M.
      • et al.
      Incidence of and risk factors for bowel ischemia after abdominal aortic aneurysm repair.
      VSGNE (AAA)2003–20141 571 / 6253 583 / 88992d
       Nevidomskyte 2016
      • Nevidomskyte D.
      • Shalhub S.
      • Singh N.
      • Farokhi E.
      • Meissner M.H.
      Influence of gender on abdominal aortic aneurysm repair in the community.
      VISCOAP (IRAAA)2010–2013152 / 56696 / 16071a, 2a–b,i–j, 3c
       Deery 2016
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      NSQIP (IRAAA)2011–2014629 / 20768 (63–75) /74 (68–79)59 (52–70) /56 (52–62)4 727 / 1 04874 (68–80) /77 (71–83)55 (51–61) /53 (50–60)81a, 2a, c–e,g–i, 3a–c, 4b,d,f,g
       Locham 2019
      • Locham S.
      • Shaaban A.
      • Wang L.
      • Bandyk D.
      • Schermerhorn M.
      • Malas M.B.
      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      SVS-VQI (AAA)2003–20186 798 / 2 46569 ± 9 /71 ± 962 ± 15 /58 ± 1233 164 / 7 78673 ± 9 /75 ± 957 ± 16 /54 ± 1181a, 2a,e,h j, 3a,c, 4a–f
       Schutze 2019
      • Shutze W.
      • Shutze R.
      • Dhot P.
      • Forge M.
      • Salazar A.
      • Ogola G.O.
      • et al.
      Sex as an independent risk factor for long-term survival after endovascular aneurysm repair.
      The Heart Hospital Baylor Plano (IRAAA)2003–2009278 / 5873 ± 9 /77 ± 954 ± 12 /52 ± 1071c, 2i, 4a–d,f
       deGuerre 2020
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      NSQIP (cAAA)2011–2017950 / 31060 (55–68) /57 (52–64)740 / 27056 (51–62) /55 (51–60)81a, 2c–e,g–i, 3a
      Finland
       Laine 2017
      • Laine M.T.
      • Laukontaus S.J.
      • Sund R.
      • Aho P.S.
      • Kantonen I.
      • Albäck A.
      • et al.
      A population-based study of abdominal aortic aneurysm treatment in Finland 2000 to 2014.
      Finnish Institute for Health & Welfare (AAA)2000–20142 898 / 4141 424 / 22091a
      Sweden
       Mani 2013
      • Mani K.
      • Björck M.
      • Wanhainen A.
      Changes in the management of infrarenal abdominal aortic aneurysm disease in Sweden.
      Swedvasc (IRAAA)2006–20101 698 / 4361 669 / 32991a
      Japan
       Hoshina 2017
      • Hoshina K.
      • Ishimaru S.
      • Sasabuchi Y.
      • Yasunaga H.
      • Komori K.
      Outcomes of endovascular repair for abdominal aortic aneurysms.
      JACSM (IRAAA)2006–201531 442 / 6 56671b,c, 2i
      Multinational
       Dubois 2013
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      Canada ENGAGE (IRAAA)2009–20111 131 / 13173 ± 8 /76 ± 761 ± 12 /58 ± 1051a, 2a,d–j, 3a–c, 4a–g
       Powell 2017
      • Powell J.T.
      • Sweeting M.J.
      • Ulug P.
      • Blankensteijn J.D.
      • Lederle F.A.
      • Becquemin J.
      Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.
      EVAR -1, DREAM, OVER, ACE (IRAAA)2000–20081 233 / 711 312 / 7791a
       Storck 2017
      • Storck M.
      • Nolte T.
      • Tenholt M.
      • Maene L.
      • Maleux G.
      • Scheinert D.
      Women and men derive comparable benefits from an ultra-low-profile endograft: 1-year results of the European OVATION registry.
      European Ovation registry (IRAAA)2011–2013432 / 6973 (46–91) /77 (49–90)55 (26–110) /54 (30–82)51c, 2a,i,j, 3c, 4a–d,f,g
       Varkevisser 2019
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Verhagen H.J.M.
      • Lyden S.P.
      • Schermerhorn M.L.
      Similar 5-year outcomes between female and male patients undergoing elective endovascular abdominal aortic aneurysm repair with the Ovation stent graft.
      Encore registry (IRAAA)2009–20161 045 / 25173 ± 8 /75 ± 852 ± 8 /55 ± 1051c, 2i,j, 3b,c, 4a,b,d–f
      Data are presented as median or median (interquartile range), or mean ± standard deviation, unless stated otherwise. NO = Newcastle Ottawa score; IRAAA = infrarenal AAA; cAAA = complex (juxta, para, or supra renal) AAA; ACE = Anevrysme de l’aorte abdominale, Chirurgie vs. Endoprothese trial; DAK = Gesundheit insurance database; DREAM = Dutch Randomised Endovascular Aneurysm Management trial; DSAA = Dutch Surgical Aneurysm Audit; ENGAGE = Endurant Stent Graft Natural Selection Global Postmarket registry; EVAR-1= Endovascular vs. open repair of abdominal aortic aneurysm trial; GFSO = German Federal Statistical Office; HES = Hospital Episode Statistics; JACSM= JApan Committee for Stentgraft Management registry; NVR = National Vascular Registry; NSQIP = American College of Surgeons’ National Surgical Quality Improvement Program; ONS = Office of National Statistics, UK; OVER = Open vs. Endovascular Repair trial; Swedvasc = Swedish vascular registry; SVS-VQI = Society for Vascular Surgery, Vascular Quality Initiative; VISCOAP = Washington State’s Vascular Interventional Surgical Care and Outcomes Assessment Program; VSGNE = Vascular Study Group of New England database.
      Reported outcomes: Mortality: 1a, 30 d; 1b, in hospital; 1c long term. Peri/post-operative complications: 2a, blood transfusion, 2b, arterial injury, 2c, limb ischaemia, 2d, bowel ischaemia, 2e, cardiac, 2f, respiratory, 2g, neurological and 2h, renal complications, 2i, re-intervention and 2j, endoleaks. Duration of treatment: 3a operative time, 3b length of intensive care and 3c hospital stay. Pre-operative comorbidities and risk factors: 4a cardiovascular, 4b, respiratory, 4c, renal, 4d, diabetes, 4e, peripheral vascular disease, 4f, smoker, 4g, comorbidity score.

      Mortality outcomes

      Overall, 13 studies (12 374 women, 50 387 men) reported 30 day mortality for OAR, ranging from 3.64% – 9.53% for women and 1.35% – 6.81% for men. Cumulative analysis demonstrated statistically significantly higher odds of death for women, without evidence of heterogeneity (OR [95% CI] 1.49 [1.37 – 1.61], p < .001, I2 = 0) (Fig. 2). Reported 30 day mortality outcomes for EVAR, from 15 non-conflicting studies (18 780 women, 93 160 men), ranged from 0 – 6.29% for women and 0.57% – 2.67% for men. Cumulative analysis demonstrated an even greater differential mortality risk for EVAR (OR 1.86 [1.59 – 2.17], p < .001, I2 = 23) (Fig. 2). Pooled analysis of 30 day and/or in hospital mortality reporting demonstrated similar results (OAR OR 1.47 [1.38 – 1.57], p < .001, I2 = 0; EVAR OR 1.77 [1.51 – 2.08], p < .001, I2 = 48) (Supplementary Fig. S6).
      • Trenner M.
      • Salvermoser M.
      • Busch A.
      • Reutersberg B.
      • Eckstein H.
      • Kuehnl A.
      Effect modification of sex and age for the outcome relationship in abdominal aortic aneurysm treatment: German Diagnosis Related Groups Statistics from 2005 to 2014.
      • Sidloff D.A.
      • Saratzis A.
      • Sweeting M.J.
      • Michaels J.
      • Powell J.T.
      • Thompson S.G.
      • et al.
      Sex differences in mortality after abdominal aortic aneurysm repair in the UK.
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
      • Paty P.S.K.
      • et al.
      Women derive less benefit from elective endovascular aneurysm repair than men.
      • Indrakusuma R.
      • Jalalzadeh H.
      • Vahl A.C.
      • Koelemay M.J.W.
      • Balm R.
      Editor’s Choice - Sex related differences in peri-operative mortality after elective repair of an asymptomatic abdominal aortic aneurysm in the Netherlands: a retrospective analysis of 2013 to 2018.
      • Ramanan B.
      • Gupta P.K.
      • Sundaram A.
      • Gupta H.
      • Johanning J.M.
      • Lynch T.G.
      • et al.
      Development of a risk index for prediction of mortality after open aortic aneurysm repair.
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      • Desai M.
      • Choke E.
      • Sayers R.D.
      • Nath M.
      • Bown M.J.
      Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men.
      • Lowry D.
      • Singh J.
      • Mytton J.
      • Tiwari A.
      Sex-related outcome inequalities in endovascular aneurysm repair.
      • Powell J.T.
      • Sweeting M.J.
      • Ulug P.
      • Blankensteijn J.D.
      • Lederle F.A.
      • Becquemin J.
      Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.
      ,
      • Chung C.
      • Tadros R.
      • Torres M.
      • Malik R.
      • Ellozy S.
      • Faries P.
      • et al.
      From the Midwestern Vascular Surgical Society: Evolution of gender-related differences in outcomes from two decades of endovascular aneurysm repair.
      ,
      • Behrendt C.
      • Kreutzburg T.
      • Kuchenbecker J.
      • Panuccio G.
      • Dankhoff M.
      • Spanos K.
      • et al.
      Female sex and outcomes after endovascular aneurysm repair for abdominal aortic aneurysm: a propensity score matched cohort analysis.
      ,
      • Schermerhorn M.L.
      • Bensley R.P.
      • Giles K.A.
      • Hurks R.
      • O'Malley A.J.
      • Cotterill P.
      • et al.
      Changes in abdominal aortic aneurysm rupture and short term mortality 1995–2008.
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      • Mani K.
      • Björck M.
      • Wanhainen A.
      Changes in the management of infrarenal abdominal aortic aneurysm disease in Sweden.
      • Skibba A.A.
      • Evans J.R.
      • Hopkins S.P.
      • Yoon H.R.
      • Katras T.
      • Kalb H.
      • et al.
      Reconsidering gender relative to risk of rupture in the contemporary management of abdominal aortic aneurysms.
      • Nevidomskyte D.
      • Shalhub S.
      • Singh N.
      • Farokhi E.
      • Meissner M.H.
      Influence of gender on abdominal aortic aneurysm repair in the community.
      • Laine M.T.
      • Laukontaus S.J.
      • Sund R.
      • Aho P.S.
      • Kantonen I.
      • Albäck A.
      • et al.
      A population-based study of abdominal aortic aneurysm treatment in Finland 2000 to 2014.
      ,
      • Locham S.
      • Shaaban A.
      • Wang L.
      • Bandyk D.
      • Schermerhorn M.
      • Malas M.B.
      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      • Hoshina K.
      • Ishimaru S.
      • Sasabuchi Y.
      • Yasunaga H.
      • Komori K.
      Outcomes of endovascular repair for abdominal aortic aneurysms.
      Figure 2
      Figure 2Comparison of 30 day mortality for men and women following (A) open (OAR) and (B) endovascular aneurysm repair (EVAR). M-H = Mantel-Haenszel; OR = odds ratio; CI = confidence interval.
      Few papers reported risk adjusted ORs for 30 day/in hospital mortality, but cumulative analysis revealed consistent outcomes for OAR (OR 1.45 [1.21 – 1.72], p < .001, I2 = 19) and EVAR (OR 1.86 [1.43 – 2.40], p < .001, I2 = 16), with only minor heterogeneity (Fig. 3).
      • Sidloff D.A.
      • Saratzis A.
      • Sweeting M.J.
      • Michaels J.
      • Powell J.T.
      • Thompson S.G.
      • et al.
      Sex differences in mortality after abdominal aortic aneurysm repair in the UK.
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
      • Paty P.S.K.
      • et al.
      Women derive less benefit from elective endovascular aneurysm repair than men.
      • Indrakusuma R.
      • Jalalzadeh H.
      • Vahl A.C.
      • Koelemay M.J.W.
      • Balm R.
      Editor’s Choice - Sex related differences in peri-operative mortality after elective repair of an asymptomatic abdominal aortic aneurysm in the Netherlands: a retrospective analysis of 2013 to 2018.
      • Ramanan B.
      • Gupta P.K.
      • Sundaram A.
      • Gupta H.
      • Johanning J.M.
      • Lynch T.G.
      • et al.
      Development of a risk index for prediction of mortality after open aortic aneurysm repair.
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      • Desai M.
      • Choke E.
      • Sayers R.D.
      • Nath M.
      • Bown M.J.
      Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men.
      • Lowry D.
      • Singh J.
      • Mytton J.
      • Tiwari A.
      Sex-related outcome inequalities in endovascular aneurysm repair.
      ,
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      While women were slightly older at the time of operation (OAR mean difference (MD) 2.31 years [1.80 – 2.83], p < .001, I2 = 88; EVAR MD 2.57 years [2.09 – 3.05], p < .001, I2 = 91), sufficient data reporting enabled meta-regression for EVAR, which showed no statistically significant association between increased age difference and log mortality odds for women (n = 11, βi = 0.086 (se = 0.14), p = .53, tau2 = 0.02) (Table 2).
      • Sidloff D.A.
      • Saratzis A.
      • Sweeting M.J.
      • Michaels J.
      • Powell J.T.
      • Thompson S.G.
      • et al.
      Sex differences in mortality after abdominal aortic aneurysm repair in the UK.
      ,
      • Indrakusuma R.
      • Jalalzadeh H.
      • Vahl A.C.
      • Koelemay M.J.W.
      • Balm R.
      Editor’s Choice - Sex related differences in peri-operative mortality after elective repair of an asymptomatic abdominal aortic aneurysm in the Netherlands: a retrospective analysis of 2013 to 2018.
      ,
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      • Desai M.
      • Choke E.
      • Sayers R.D.
      • Nath M.
      • Bown M.J.
      Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men.
      • Lowry D.
      • Singh J.
      • Mytton J.
      • Tiwari A.
      Sex-related outcome inequalities in endovascular aneurysm repair.
      ,
      • Chung C.
      • Tadros R.
      • Torres M.
      • Malik R.
      • Ellozy S.
      • Faries P.
      • et al.
      From the Midwestern Vascular Surgical Society: Evolution of gender-related differences in outcomes from two decades of endovascular aneurysm repair.
      ,
      • Trenner M.
      • Kuehnl A.
      • Reutersberg B.
      • Salvermoser M.
      • Eckstein H.
      Nationwide analysis of risk factors for in-hospital mortality in patients undergoing abdominal aortic aneurysm repair.
      ,
      • Locham S.
      • Shaaban A.
      • Wang L.
      • Bandyk D.
      • Schermerhorn M.
      • Malas M.B.
      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      ,
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      ,
      • Storck M.
      • Nolte T.
      • Tenholt M.
      • Maene L.
      • Maleux G.
      • Scheinert D.
      Women and men derive comparable benefits from an ultra-low-profile endograft: 1-year results of the European OVATION registry.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Verhagen H.J.M.
      • Lyden S.P.
      • Schermerhorn M.L.
      Similar 5-year outcomes between female and male patients undergoing elective endovascular abdominal aortic aneurysm repair with the Ovation stent graft.
      • Shutze W.
      • Shutze R.
      • Dhot P.
      • Forge M.
      • Salazar A.
      • Ogola G.O.
      • et al.
      Sex as an independent risk factor for long-term survival after endovascular aneurysm repair.
      Women were also likely to be operated at a smaller aortic diameter than men; the difference was attenuated for EVAR and statistically significant heterogeneity was observed (OAR MD −4.93 mm [95% CI −6.71 – −3.14], p < .001, I2 = 95; EVAR MD −2.10 mm [95% CI −2.66 – −1.55], p < .001, I2 = 84)
      • Sidloff D.A.
      • Saratzis A.
      • Sweeting M.J.
      • Michaels J.
      • Powell J.T.
      • Thompson S.G.
      • et al.
      Sex differences in mortality after abdominal aortic aneurysm repair in the UK.
      ,
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
      • Paty P.S.K.
      • et al.
      Women derive less benefit from elective endovascular aneurysm repair than men.
      ,
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      ,
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      ,
      • Locham S.
      • Shaaban A.
      • Wang L.
      • Bandyk D.
      • Schermerhorn M.
      • Malas M.B.
      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      ,
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      ,
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      ,
      • Storck M.
      • Nolte T.
      • Tenholt M.
      • Maene L.
      • Maleux G.
      • Scheinert D.
      Women and men derive comparable benefits from an ultra-low-profile endograft: 1-year results of the European OVATION registry.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Verhagen H.J.M.
      • Lyden S.P.
      • Schermerhorn M.L.
      Similar 5-year outcomes between female and male patients undergoing elective endovascular abdominal aortic aneurysm repair with the Ovation stent graft.
      • Shutze W.
      • Shutze R.
      • Dhot P.
      • Forge M.
      • Salazar A.
      • Ogola G.O.
      • et al.
      Sex as an independent risk factor for long-term survival after endovascular aneurysm repair.
      (Table 2). Assessment of the influence of other comorbidities on mortality was limited by heterogeneity, secondary to variation in definitions and reporting of comorbidities and patient selection, although cardiac disease appeared more common in men (OAR OR 0.72 [0.59 – 0.88]; EVAR OR 0.65 [0.48 – 0.87]) and respiratory disease more common in women (OAR OR 1.51 [1.23 – 1.86]; EVAR OR 1.26 [1.08 – 1.46]). Full data for these and other comorbidities are given in Supplementary Table S5.
      Figure 3
      Figure 3Comparison of risk adjusted odds ratios (OR) of 30 day mortality for men and women following (A) open (OAR) and (B) endovascular aneurysm repair (EVAR). CI = confidence interval; IV = inverse variance.
      To investigate whether sex specific differences in mortality had changed over time, meta-regression, using study midpoint as a covariate, was conducted. While the mortality OR of women for both OAR and EVAR have increased slightly over the last 20 years, this finding was statistically non-significant (OAR: n = 15, βi = 0.087 (se = 0.019), p = .65, tau2 = 0; EVAR: n = 18, βi = 0.014 (se = 0.034), p = .69, tau2 = 0.05) (Fig. 4).
      • Trenner M.
      • Salvermoser M.
      • Busch A.
      • Reutersberg B.
      • Eckstein H.
      • Kuehnl A.
      Effect modification of sex and age for the outcome relationship in abdominal aortic aneurysm treatment: German Diagnosis Related Groups Statistics from 2005 to 2014.
      • Sidloff D.A.
      • Saratzis A.
      • Sweeting M.J.
      • Michaels J.
      • Powell J.T.
      • Thompson S.G.
      • et al.
      Sex differences in mortality after abdominal aortic aneurysm repair in the UK.
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
      • Paty P.S.K.
      • et al.
      Women derive less benefit from elective endovascular aneurysm repair than men.
      • Indrakusuma R.
      • Jalalzadeh H.
      • Vahl A.C.
      • Koelemay M.J.W.
      • Balm R.
      Editor’s Choice - Sex related differences in peri-operative mortality after elective repair of an asymptomatic abdominal aortic aneurysm in the Netherlands: a retrospective analysis of 2013 to 2018.
      • Ramanan B.
      • Gupta P.K.
      • Sundaram A.
      • Gupta H.
      • Johanning J.M.
      • Lynch T.G.
      • et al.
      Development of a risk index for prediction of mortality after open aortic aneurysm repair.
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      • Desai M.
      • Choke E.
      • Sayers R.D.
      • Nath M.
      • Bown M.J.
      Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men.
      • Lowry D.
      • Singh J.
      • Mytton J.
      • Tiwari A.
      Sex-related outcome inequalities in endovascular aneurysm repair.
      • Powell J.T.
      • Sweeting M.J.
      • Ulug P.
      • Blankensteijn J.D.
      • Lederle F.A.
      • Becquemin J.
      Meta-analysis of individual-patient data from EVAR-1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years.
      ,
      • Chung C.
      • Tadros R.
      • Torres M.
      • Malik R.
      • Ellozy S.
      • Faries P.
      • et al.
      From the Midwestern Vascular Surgical Society: Evolution of gender-related differences in outcomes from two decades of endovascular aneurysm repair.
      ,
      • Behrendt C.
      • Kreutzburg T.
      • Kuchenbecker J.
      • Panuccio G.
      • Dankhoff M.
      • Spanos K.
      • et al.
      Female sex and outcomes after endovascular aneurysm repair for abdominal aortic aneurysm: a propensity score matched cohort analysis.
      ,
      • Schermerhorn M.L.
      • Bensley R.P.
      • Giles K.A.
      • Hurks R.
      • O'Malley A.J.
      • Cotterill P.
      • et al.
      Changes in abdominal aortic aneurysm rupture and short term mortality 1995–2008.
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      • Mani K.
      • Björck M.
      • Wanhainen A.
      Changes in the management of infrarenal abdominal aortic aneurysm disease in Sweden.
      • Skibba A.A.
      • Evans J.R.
      • Hopkins S.P.
      • Yoon H.R.
      • Katras T.
      • Kalb H.
      • et al.
      Reconsidering gender relative to risk of rupture in the contemporary management of abdominal aortic aneurysms.
      • Nevidomskyte D.
      • Shalhub S.
      • Singh N.
      • Farokhi E.
      • Meissner M.H.
      Influence of gender on abdominal aortic aneurysm repair in the community.
      • Laine M.T.
      • Laukontaus S.J.
      • Sund R.
      • Aho P.S.
      • Kantonen I.
      • Albäck A.
      • et al.
      A population-based study of abdominal aortic aneurysm treatment in Finland 2000 to 2014.
      ,
      • Locham S.
      • Shaaban A.
      • Wang L.
      • Bandyk D.
      • Schermerhorn M.
      • Malas M.B.
      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      • Hoshina K.
      • Ishimaru S.
      • Sasabuchi Y.
      • Yasunaga H.
      • Komori K.
      Outcomes of endovascular repair for abdominal aortic aneurysms.
      Figure 4
      Figure 4Meta-regression examining association between midpoint of study and log odds of 30 day/in hospital mortality for women vs. men following (A) open (OAR) and (B) endovascular aneurysm repair (EVAR). No statistically significant trend in log odds of female mortality over time was observed. Studies are labelled by first author and year of publication.

      Peri-operative outcomes

      Women were more likely to receive blood transfusion (OAR, OR 1.83 [1.53 – 2.19]; EVAR OR 2.17 [2.07 – 2.28]) (Fig. 3).
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      ,
      • Behrendt C.
      • Kreutzburg T.
      • Kuchenbecker J.
      • Panuccio G.
      • Dankhoff M.
      • Spanos K.
      • et al.
      Female sex and outcomes after endovascular aneurysm repair for abdominal aortic aneurysm: a propensity score matched cohort analysis.
      ,
      • Nevidomskyte D.
      • Shalhub S.
      • Singh N.
      • Farokhi E.
      • Meissner M.H.
      Influence of gender on abdominal aortic aneurysm repair in the community.
      ,
      • Trenner M.
      • Kuehnl A.
      • Reutersberg B.
      • Salvermoser M.
      • Eckstein H.
      Nationwide analysis of risk factors for in-hospital mortality in patients undergoing abdominal aortic aneurysm repair.
      ,
      • Locham S.
      • Shaaban A.
      • Wang L.
      • Bandyk D.
      • Schermerhorn M.
      • Malas M.B.
      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      An increased risk of arterial injury for women undergoing EVAR was also observed (OR 3.02 [1.62 – 5.65], p < .001, I2 = 49).
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
      • Paty P.S.K.
      • et al.
      Women derive less benefit from elective endovascular aneurysm repair than men.
      ,
      • Chung C.
      • Tadros R.
      • Torres M.
      • Malik R.
      • Ellozy S.
      • Faries P.
      • et al.
      From the Midwestern Vascular Surgical Society: Evolution of gender-related differences in outcomes from two decades of endovascular aneurysm repair.
      ,
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      ,
      • Nevidomskyte D.
      • Shalhub S.
      • Singh N.
      • Farokhi E.
      • Meissner M.H.
      Influence of gender on abdominal aortic aneurysm repair in the community.
      Operative time (minutes) was statistically significantly lower for women compared with men for OAR (MD −14.98 [−18.45 – −11.51], p < .001, I2 = 0), and not statistically significantly different for EVAR (MD 4.33 [−0.99 – 9.65], p = .11, I2 = 79) (Supplementary Table S4).
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      ,
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      ,
      • Locham S.
      • Shaaban A.
      • Wang L.
      • Bandyk D.
      • Schermerhorn M.
      • Malas M.B.
      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      ,
      • Storck M.
      • Nolte T.
      • Tenholt M.
      • Maene L.
      • Maleux G.
      • Scheinert D.
      Women and men derive comparable benefits from an ultra-low-profile endograft: 1-year results of the European OVATION registry.

      Post-operative in hospital/30 day complications

      Statistically significant sex specific differences in post-operative outcomes are illustrated in Fig. 5 (and Supplement S4). No complications were more common in men than women. The difference for cardiac complications, defined as myocardial ischaemia (with inclusion of congestive cardiac failure in three studies), was not statistically significant for women undergoing OAR, but was statistically significantly higher for women after EVAR, (OR 1.19 [1.03 – 1.37], p < .001, I2 = 0).
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
      • Paty P.S.K.
      • et al.
      Women derive less benefit from elective endovascular aneurysm repair than men.
      ,
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      ,
      • Desai M.
      • Choke E.
      • Sayers R.D.
      • Nath M.
      • Bown M.J.
      Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men.
      ,
      • Behrendt C.
      • Kreutzburg T.
      • Kuchenbecker J.
      • Panuccio G.
      • Dankhoff M.
      • Spanos K.
      • et al.
      Female sex and outcomes after endovascular aneurysm repair for abdominal aortic aneurysm: a propensity score matched cohort analysis.
      ,
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      ,
      • Trenner M.
      • Kuehnl A.
      • Reutersberg B.
      • Salvermoser M.
      • Eckstein H.
      Nationwide analysis of risk factors for in-hospital mortality in patients undergoing abdominal aortic aneurysm repair.
      ,
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      ,
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      Respiratory complications (pneumonia or acute respiratory distress), were observed to be statistically significantly more common for women after both forms of repair (OAR OR 1.40 [1.28 – 1.53], p < .001, I2 = 0; EVAR OR 1.44 [1.17 – 1.77], p < .001, I2 = 14).
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
      • Paty P.S.K.
      • et al.
      Women derive less benefit from elective endovascular aneurysm repair than men.
      ,
      • Desai M.
      • Choke E.
      • Sayers R.D.
      • Nath M.
      • Bown M.J.
      Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men.
      ,
      • Chung C.
      • Tadros R.
      • Torres M.
      • Malik R.
      • Ellozy S.
      • Faries P.
      • et al.
      From the Midwestern Vascular Surgical Society: Evolution of gender-related differences in outcomes from two decades of endovascular aneurysm repair.
      ,
      • Behrendt C.
      • Kreutzburg T.
      • Kuchenbecker J.
      • Panuccio G.
      • Dankhoff M.
      • Spanos K.
      • et al.
      Female sex and outcomes after endovascular aneurysm repair for abdominal aortic aneurysm: a propensity score matched cohort analysis.
      ,
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      ,
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      ,
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      Renal complications, defined as acute renal failure requiring intense medical treatment or dialysis (or for Trenner et al. a coded diagnosis of renal infarction), were not more common for women following OAR, but were statistically significantly more likely following EVAR (OR 1.46 [1.25 – 1.72], p < .001, I2 = 0).
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
      • Paty P.S.K.
      • et al.
      Women derive less benefit from elective endovascular aneurysm repair than men.
      ,
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      ,
      • Desai M.
      • Choke E.
      • Sayers R.D.
      • Nath M.
      • Bown M.J.
      Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men.
      ,
      • Behrendt C.
      • Kreutzburg T.
      • Kuchenbecker J.
      • Panuccio G.
      • Dankhoff M.
      • Spanos K.
      • et al.
      Female sex and outcomes after endovascular aneurysm repair for abdominal aortic aneurysm: a propensity score matched cohort analysis.
      ,
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      ,
      • Trenner M.
      • Kuehnl A.
      • Reutersberg B.
      • Salvermoser M.
      • Eckstein H.
      Nationwide analysis of risk factors for in-hospital mortality in patients undergoing abdominal aortic aneurysm repair.
      ,
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      ,
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      An increase in the risk of neurological complication (acute cerebrovascular accident) was not observed for women following OAR, whereas an increase for EVAR was observed (OR 2.08 [1.01 – 4.29], p < .050, I2 = 54), but was not robust to sensitivity analysis.
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      ,
      • Desai M.
      • Choke E.
      • Sayers R.D.
      • Nath M.
      • Bown M.J.
      Sex-related trends in mortality after elective abdominal aortic aneurysm surgery between 2002 and 2013 at National Health Service hospitals in England: less benefit for women compared with men.
      ,
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      ,
      • Trenner M.
      • Kuehnl A.
      • Reutersberg B.
      • Salvermoser M.
      • Eckstein H.
      Nationwide analysis of risk factors for in-hospital mortality in patients undergoing abdominal aortic aneurysm repair.
      ,
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      ,
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      Risk of bowel ischaemia (mesenteric thrombus or embolism or colonic ischaemia) was statistically significantly greater for women for both OAR and EVAR (OAR OR 1.52 [1.34 – 1.74] p < .001, I2 = 0; EVAR OR 1.99 [1.51 – 2.62], p < .001, I2 = 2).
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
      • Paty P.S.K.
      • et al.
      Women derive less benefit from elective endovascular aneurysm repair than men.
      ,
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      ,
      • Ultee K.H.J.
      • Zettervall S.L.
      • Soden P.A.
      • Darling J.
      • Bertges D.J.
      • Verhagen H.J.M.
      • et al.
      Incidence of and risk factors for bowel ischemia after abdominal aortic aneurysm repair.
      ,
      • Behrendt C.
      • Kreutzburg T.
      • Kuchenbecker J.
      • Panuccio G.
      • Dankhoff M.
      • Spanos K.
      • et al.
      Female sex and outcomes after endovascular aneurysm repair for abdominal aortic aneurysm: a propensity score matched cohort analysis.
      ,
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      ,
      • Trenner M.
      • Kuehnl A.
      • Reutersberg B.
      • Salvermoser M.
      • Eckstein H.
      Nationwide analysis of risk factors for in-hospital mortality in patients undergoing abdominal aortic aneurysm repair.
      • Locham S.
      • Shaaban A.
      • Wang L.
      • Bandyk D.
      • Schermerhorn M.
      • Malas M.B.
      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      Lower limb ischaemia (arterial occlusion and/or major amputation), was not more likely for women for OAR, but was statistically significantly more likely for women following EVAR (OR 2.13 [1.48 – 3.06], p < .001, I2 = 75), although substantial heterogeneity was observed.
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
      • Paty P.S.K.
      • et al.
      Women derive less benefit from elective endovascular aneurysm repair than men.
      ,
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      ,
      • Behrendt C.
      • Kreutzburg T.
      • Kuchenbecker J.
      • Panuccio G.
      • Dankhoff M.
      • Spanos K.
      • et al.
      Female sex and outcomes after endovascular aneurysm repair for abdominal aortic aneurysm: a propensity score matched cohort analysis.
      ,
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      ,
      • Trenner M.
      • Kuehnl A.
      • Reutersberg B.
      • Salvermoser M.
      • Eckstein H.
      Nationwide analysis of risk factors for in-hospital mortality in patients undergoing abdominal aortic aneurysm repair.
      • Locham S.
      • Shaaban A.
      • Wang L.
      • Bandyk D.
      • Schermerhorn M.
      • Malas M.B.
      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      • De Guerre L.E.V.M.
      • Varkevisser R.R.B.
      • Swerdlow N.J.
      • Liang P.
      • Li
      • Chun
      • Dansey K.
      • et al.
      Sex differences in perioperative outcomes after complex abdominal aortic aneurysm repair.
      On average, women spent longer in intensive care compared with men following OAR (MD 0.93 [0.65 – 1.21], p < .001, I2 = 31, days), but not for EVAR.
      • Sidloff D.A.
      • Saratzis A.
      • Sweeting M.J.
      • Michaels J.
      • Powell J.T.
      • Thompson S.G.
      • et al.
      Sex differences in mortality after abdominal aortic aneurysm repair in the UK.
      ,
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      ,
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      ,
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      An increased length of hospital stay was reported for women for both OAR and EVAR, although substantial heterogeneity was observed (OAR MD 1.19 [0.65 – 1.73], p < .001, I2 = 94; EVAR MD 1.14 [0.85 – 1.44], p < .001, I2 = 95, days).
      • Sidloff D.A.
      • Saratzis A.
      • Sweeting M.J.
      • Michaels J.
      • Powell J.T.
      • Thompson S.G.
      • et al.
      Sex differences in mortality after abdominal aortic aneurysm repair in the UK.
      ,
      • Deery S.E.
      • Soden P.A.
      • Zettervall S.L.
      • Shean K.E.
      • Bodewes T.C.F.
      • Pothof A.B.
      • et al.
      Sex differences in mortality and morbidity following repair of intact abdominal aortic aneurysms.
      ,
      • Lowry D.
      • Singh J.
      • Mytton J.
      • Tiwari A.
      Sex-related outcome inequalities in endovascular aneurysm repair.
      ,
      • Chung C.
      • Tadros R.
      • Torres M.
      • Malik R.
      • Ellozy S.
      • Faries P.
      • et al.
      From the Midwestern Vascular Surgical Society: Evolution of gender-related differences in outcomes from two decades of endovascular aneurysm repair.
      ,
      • Behrendt C.
      • Kreutzburg T.
      • Kuchenbecker J.
      • Panuccio G.
      • Dankhoff M.
      • Spanos K.
      • et al.
      Female sex and outcomes after endovascular aneurysm repair for abdominal aortic aneurysm: a propensity score matched cohort analysis.
      ,
      • Lo R.C.
      • Bensley R.P.
      • Hamdan A.D.
      • Wyers M.
      • Adams J.E.
      • Schermerhorn M.L.
      Gender differences in abdominal aortic aneurysm presentation, repair, and mortality in the Vascular Study Group of New England.
      ,
      • Trenner M.
      • Kuehnl A.
      • Reutersberg B.
      • Salvermoser M.
      • Eckstein H.
      Nationwide analysis of risk factors for in-hospital mortality in patients undergoing abdominal aortic aneurysm repair.
      ,
      • Locham S.
      • Shaaban A.
      • Wang L.
      • Bandyk D.
      • Schermerhorn M.
      • Malas M.B.
      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      ,
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      ,
      • Storck M.
      • Nolte T.
      • Tenholt M.
      • Maene L.
      • Maleux G.
      • Scheinert D.
      Women and men derive comparable benefits from an ultra-low-profile endograft: 1-year results of the European OVATION registry.
      Figure 5
      Figure 5Comparison of 30 day complications for men and women following (A) open (OAR) and (B) endovascular aneurysm repair (EVAR). M-H = Mantel-Haenszel; CI = confidence interval; OR = odds ratio.
      Meta-regression to assess the influence of sex specific differences in post-operative complications on between study heterogeneity for mortality outcomes was limited by paucity of data. For OAR, insufficient data reporting prevented any evaluations. For EVAR, eight studies reported cardiac outcomes, for which a strong association between increased cardiac complications and increased female mortality was observed (βi = 2.96 (se = 1.27), p = .020, tau2 = 0.00), eight studies also reported renal complications, for which the positive association with mortality was almost statistically significant (βi = 2.50 (se = 1.31), p = .056, tau2 = 0.01) (Supplementary Fig. S7).
      • Mehta M.
      • Byrne W.J.
      • Gen F.
      • Robinson H.
      • Roddy S.P.
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      ,
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      ,
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      • Nath M.
      • Bown M.J.
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      ,
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      Insufficient data were available for multivariable regression or assessment of other covariables.

      Endograft complications

      Although type 1 endoleak (OR 1.75 [1.56 – 1.96], p < .001, I2 = 0) and any endoleak (OR 1.11 [1.02 – 1.22], p < .020, I2 = 14) were more likely to occur following EVAR for women, no statistically significant difference in the likelihood of re-intervention was observed (Supplementary Table S4).
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      ,
      • Nevidomskyte D.
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      ,
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      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      ,
      • Dubois L.
      • Novick T.V.
      • Harris J.R.
      • Derose G.
      • Forbes T.L.
      Outcomes after endovascular abdominal aortic aneurysm repair are equivalent between genders despite anatomic differences in women.
      • Hoshina K.
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      Outcomes of endovascular repair for abdominal aortic aneurysms.
      • Storck M.
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      Women and men derive comparable benefits from an ultra-low-profile endograft: 1-year results of the European OVATION registry.
      • Varkevisser R.R.B.
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      Similar 5-year outcomes between female and male patients undergoing elective endovascular abdominal aortic aneurysm repair with the Ovation stent graft.
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      Assessment of bias and sensitivity analyses

      Egger’s test suggested the presence of funnel plot asymmetry for publication bias for OAR, but cumulative findings were robust to trim and fill analysis (adjusted OR 1.45 [95% CI 1.36 – 1.55], p < .001) (Supplementary Figs and Text S8). No significant suggestion of publication bias was observed for EVAR (p = .899). Sensitivity analyses for all analyses of mortality and post-operative outcomes were robust, with the exception of the following: (1) incidence of cardiac complications following OAR were heavily weighted by data from Germany and on removal of these data a small but statistically significant increase in cardiac complications was observed for women (OR 1.27 (95% CI 1.04 – 1.55), p = .020, I2 = 32); (2) the increase in neurological complications following EVAR for women was not robust to sensitivity analysis; (3) incidence of any endoleak was heavily weighted by data from the USA and not robust on sensitivity analysis. The sex specific differences in 30 day mortality persisted in both studies reporting infrarenal AAAs alone and studies including juxta-, para-, or suprarenal AAA, although in the latter group of studies ORs for the sex specific disparity may have increased slightly for EVAR (Supplementary Table S4). Despite significant heterogeneity, sensitivity analysis was robust for the pre-operative variables of sex specific differences in age and AAA diameter.

      Discussion

      This systematic review demonstrated a significantly higher 30 day mortality risk for women following OAR, with an increased risk differential for EVAR (OR 1.49 vs. OR 1.86, respectively), which meta-regression showed has not been ameliorated by modern practice. The study also demonstrated that sex specific differences varied with type of repair, allowing insight into the increased mortality risk differential for EVAR. For both OAR and EVAR, women were at increased risk of respiratory complications, bowel ischaemia, and need for blood transfusion: no post-operative complication was more common in men and procedure times were similar for both sexes. Following EVAR, women were also at increased risk of cardiac and renal complications as well as limb ischaemia and arterial injury. These findings provide a shocking presentation of gender disparity in AAA repair outcomes and raise questions regarding procedure specific causes for the inequalities observed.
      It is tempting to attribute the increased risks for women undergoing EVAR to technical difficulties secondary to challenging anatomy (e.g., more tortuous access vessels and shorter angulated aneurysmal necks). However, as the outcomes in this paper are for the subset of women deemed anatomically suitable for EVAR, and operative times were comparable, it is unlikely that anatomical differences alone can sufficiently explain the disparities in outcomes observed.
      • Ulug P.
      • Sweeting M.J.
      • Thompson S.G.
      • Powell J.T.
      Morphological suitability for endovascular repair, non-intervention rates, and operative mortality in women and men assessed for intact abdominal aortic aneurysm repair: systematic reviews with meta-analysis.
      ,
      • Sweet M.P.
      • Fillinger M.F.
      • Morrison T.M.
      • Abel D.
      The influence of gender and aortic aneurysm size on eligibility for endovascular abdominal aortic aneurysm repair.
      Moreover, the development of low profile delivery devices to facilitate challenging access, and innovative solutions for hostile neck anatomy have greatly reduced many of the traditional obstacles to endovascular repair.
      • Jordan Jr., W.D.
      • Mehta M.
      • Varnagy D.
      • Moore Jr., W.M.
      • Arko F.R.
      • Joye J.
      • et al.
      Results of the ANCHOR prospective, multicenter registry of EndoAnchors for type Ia endoleaks and endograft migration in patients with challenging anatomy.
      • Kuten D.
      • Krajcer Z.
      Progress in endovascular aortic repair for women.
      • Cohnert T.
      • Konstantiniuk P.
      • Sieg G.
      • Oswald W.
      • Portugaller H.
      Abdominal aortic aneurysm treatment in women. Excellent long-term results for endovascular aneurysm repair morphologic changes in renal and superior mesenteric arteries after fenestrated endovascular aortic repair.
      Ultimately, in the elective setting, challenging anatomy does not absolve the surgeon of responsibility, as there are multiple avenues to reduce risk.
      Bowel ischaemia carries a high risk of mortality and was statistically significantly greater for women following both OAR and EVAR.
      • Ultee K.H.J.
      • Zettervall S.L.
      • Soden P.A.
      • Darling J.
      • Bertges D.J.
      • Verhagen H.J.M.
      • et al.
      Incidence of and risk factors for bowel ischemia after abdominal aortic aneurysm repair.
      This may in part be the result of differences in systemic perfusion or blood loss (noted by Ultee et al. as a risk factor for bowel ischaemia [OR 2.0]), in operative strategies (e.g., proximal extension or clamp location, hypogastric artery exclusion), or caused by increased embolisation.
      • Ultee K.H.J.
      • Zettervall S.L.
      • Soden P.A.
      • Darling J.
      • Bertges D.J.
      • Verhagen H.J.M.
      • et al.
      Incidence of and risk factors for bowel ischemia after abdominal aortic aneurysm repair.
      ,
      • Gurakar M.
      • Locham S.
      • Alshaikh H.N.
      Risk factors and outcomes for bowel ischemia after open and endovascular abdominal aortic aneurysm repair.
      ,
      • Perry R.J.T.
      • Martin M.J.
      • Eckert M.J.
      • Sohn V.Y.
      • Steele S.R.
      Colonic ischemia complicating open vs endovascular abdominal aortic aneurysm repair.
      • Williamson J.S.
      • Ambler G.K.
      • Twine C.P.
      • Williams I.M.
      • Williams G.L.
      Elective repair of abdominal aortic aneurysm and the risk of colonic ischaemia: systematic review and meta-analysis.
      • Björck M.
      • Boyle J.R.
      Colonic ischaemia - a devastating complication of abdominal aortic aneurysm repair.
      Emboli are an important factor in the pathogenesis of post-operative bowel (and renal) ischaemia, and as EVAR is associated with twice the number of emboli as OAR, increased embolisation in women could contribute to the greater risk differential observed for EVAR.
      • Ribero M.
      • Oderich G.S.
      • Macedo T.
      • Vrtiska T.J.
      • Hofer J.
      • Chini J.
      • et al.
      Assessment of aortic wall thrombus predicts outcomes of endovascular repair of complex aortic aneurysms using fenestrated and branched endografts.
      • Dadian N.
      • Ohki T.
      • Veith F.J.
      • Edelman M.
      • Mehta M.
      • Lipsitz E.C.
      • et al.
      Overt colon ischemia after endovascular aneurysm repair: the importance of microembolization as an etiology.
      • Thompson M.M.
      • Smith J.
      • Naylor A.R.
      • Smith G.
      • Bell P.
      Microembolization during endovascular and conventional aneurysm repair.
      This requires further research.
      Acute kidney injury is also associated with a two fold increase in mortality and cardiovascular morbidity, and may contribute to the increased mortality risk for women following EVAR.
      • Odutayo A.
      • Wong C.X.
      • Farkouh M.
      • Altman D.G.
      • Hopewell S.
      • Emdin C.A.
      • et al.
      AKI and long-term risk for cardiovascular events and mortality.
      ,
      • Thakar C.V.
      • Christianson A.
      • Freyberg R.
      • Almenoff P.
      • Render M.L.
      Incidence and outcomes of acute kidney injury in intensive care units: a Veterans Administration study.
      Sex specific differences in kidney injury may also result from embolism, anatomical differences (e.g., closer proximity of the renal arteries, orificial disease, angulation), selection of suboptimal endovascular strategies (e.g., renal artery coverage), or iatrogenic injury (e.g., contrast nephropathy or intimal damage).
      • Locham S.
      • Shaaban A.
      • Wang L.
      • Bandyk D.
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      • Malas M.B.
      Impact of gender on outcomes following abdominal aortic aneurysm repair.
      ,
      • Oderich G.S.
      • Tenorio E.R.
      Optimizing outcomes of endovascular aneurysm repair in patients with CKD.
      Renal protective strategies such as pre-hydration, avoidance of renotoxic medication, judicious use of contrast, and a careful operative approach with renal preservation, can greatly reduce the risk of renal injury and should be strictly implemented for women.
      • Oderich G.S.
      • Tenorio E.R.
      Optimizing outcomes of endovascular aneurysm repair in patients with CKD.
      ,
      KDIGO Clinical Practice Guideline for Acute Kidney Injury.
      EVAR access complications are associated with four times the odds of peri-operative death, while conversion to open, rather than planned cutdown, is associated with a higher risk of major complication.
      • O'Donnell T.F.X.
      • Deery S.E.
      • Boitano L.T.
      • Schermerhorn L.
      • Siracuse J.J.
      • Clouse W.D.
      • et al.
      The long-term implications of access complications during EVAR.
      In this study double the risk of limb ischaemia (and transfusion) for women undergoing EVAR, combined with a three fold increased risk of arterial injury and without evidence of increased operation time (indicative of increased complexity) was observed. Therefore it is certainly possible that limb access complications, with an iatrogenic component, are likely to have contributed to the increased mortality risk for women, and present a target for quality improvement through emphasis on strategic planning.
      • O'Donnell T.F.X.
      • Deery S.E.
      • Boitano L.T.
      • Schermerhorn L.
      • Siracuse J.J.
      • Clouse W.D.
      • et al.
      The long-term implications of access complications during EVAR.
      Differential sex specific mortality risk remained following adjustment for confounding risk factors, and analysis of pre-operative comorbid status, although very limited by heterogeneity, did not demonstrate clear evidence of increased vulnerability among women undergoing AAA repair overall. However, the increased risk of respiratory complications and longer length of stay may suggest a role for pre-operative respiratory physiotherapy and exercise.
      • Nardi P.
      • Pellegrino A.
      • Pisano C.
      • Vacirca S.R.
      • Anselmi D.
      • Saulle S.
      • et al.
      The effect of preoperative respiratory physiotherapy and motor exercise in patients undergoing elective cardiac surgery: short-term results.
      In addition, while men were more often reported to have pre-operative cardiac disease, following EVAR, women were more likely to suffer cardiac complications. This may reflect failure to recognise and investigate comorbidity before EVAR, secondary to reduced index of suspicion and unconscious or systemic bias, which limits the ability to optimise the patient’s health status prior to repair and may increase the risk of adverse events.
      • Alabas O.A.
      • Gale C.P.
      • Hall M.
      • Rutherford M.J.
      • Szummer K.
      • Alfredsson J.
      • et al.
      Sex differences in treatments, relative survival, and excess mortality following acute myocardial infarction: national cohort study using the SWEDEHEART registry.
      Better standardisation and reporting of comorbidity assessment is needed to allow future studies to robustly analyse how this affects the differential in sex specific mortality risk.
      This meta-analysis was limited because of heterogeneity in patient selection, threshold for treatment, publication bias, and a lack of systematic reporting of comorbidity and complications, which prevented further meta-regression. Although cumulative analysis of retrospective data cannot offer the same level of detail or control for confounding factors as a well designed prospective analysis, the present findings of increased mortality and complications for women were robust to sensitivity analysis and warrant further detailed investigation. While women were more likely to have complications and more likely to die in hospital, it was not possible to directly assess “failure to rescue” (FTR, death directly attributed to a significant post-surgical complication) on cumulative analysis, as this was not reported as a specific outcome within included studies. Female sex has been reported previously as an independent risk factor for FTR among patients aged ≥ 80 years undergoing AAA repair (OR 1.95).
      • Hicks C.
      • O’Kelly A.
      • Obeid T.
      • Locham S.
      • Malas M.
      Predicting failure to rescue after abdominal aortic aneurysm repair in elderly patients.
      Therefore, FTR could be considered a useful outcome for future studies evaluating sex specific disparity. A further limitation of this study was that to reduce heterogeneity, analysis was limited to intact AAA repair, and therefore does not include analysis of sex specific differences in patients with an index presentation of AAA rupture.
      Women have been overlooked in the field of vascular surgery, and under represented in key randomised trials, which form the foundation of evidence based care.
      • Lo R.C.
      • Schermerhorn M.L.
      Abdominal aortic aneurysms in women.
      Therefore, it remains possible that advances in modern practice, with best practice guidance and endovascular therapy primarily based on evidence for AAA repair in men, are not suitable for women.
      • Hannawa K.
      • Eliason J.
      • Upchurch J.
      Gender differences in abdominal aortic aneurysms.
      For example, the introduction of screening in men only, leading to timely identification and treatment, may have contributed to widening of the risk differential.
      • Sweeting M.J.
      • Masconi K.L.
      • Jones E.
      • Ulug P.
      • Glover M.J.
      • Michaels J.A.
      • et al.
      Analysis of clinical benefit, harms, and cost-effectiveness of screening women for abdominal aortic aneurysm.
      Greater understanding of the differences in the pathophysiology of AAAs in women, pertinent risk factors, and differences in provision of care could enable a tailored pathway and narrowing of this outcome disparity.
      This study demonstrates that the risk of mortality following AAA repair is consistently higher for women. This may be secondary to sex specific differences in post-operative complications, which differ for OAR and EVAR, or unequal pre-operative recognition and optimisation of risk factors. Such glaring disparity cannot and should not remain unchallenged. This study indicates key areas to target including reduction in arterial injury and emboli and improved renal protection. Just as changes to pre-operative optimisation and dedicated multidisciplinary care have radically improved overall outcomes for all patients with AAA repair; an intelligent approach to quality improvement combined with proportionate inclusion of women in prospective research, has the potential to dramatically reduce the gender gap following AAA repair.

      Conflict of interest

      None.

      Funding

      None.

      Appendix A. Supplementary data

      The following is the Supplementary data to this article:

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      Linked Article

      • Extra Caution Required in Elective Abdominal Aortic Aneurysm Repair for Women
        European Journal of Vascular and Endovascular SurgeryVol. 62Issue 3
        • Preview
          Pouncey et al. have conducted a relevant meta-analysis comparing the short term outcomes of intact abdominal aortic aneurysm (AAA) repair in women vs. men.1 Worse overall outcomes for vascular procedures in women have been reported previously, including for AAA repair.2,3 However, AAA management has undergone deep transformations, mainly related to advances in endoluminal devices and continuous improvement of open and endovascular techniques.4 Additionally, we have seen a gradual improvement in peri-operative care, potentially reducing or eliminating these sex related discrepancies.
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