title: Meta- analysis and meta-regression analysis of the associations between sex and the operative outcomes of carotid endarterectomy.
abstract: BACKGROUND
  Subgroup analyses from randomized controlled trials (RCT) of carotid endarterectomy (CEA) for both symptomatic and asymptomatic carotid stenosis suggest less benefit in women compared to men, due partly to higher age-independent peri-operative risk. However, a meta-analysis of case series and databases focussing on CEA-related gender differences has never been investigated.
  
  
  METHODS
  A systematic review of all available publications (including case series, databases and RCTs) reporting data on the association between sex and procedural risk of stroke and/or death following CEA from 1980 to 2015 was investigated. Pooled Peto odds ratios of the procedural risk of stroke and/or death were obtained by Mantel-Haenszel random-effects meta-analysis. The I(2) statistic was used as a measure of heterogeneity. Potential publication bias was assessed with the Egger test and represented graphically with Begg funnel plots of the natural log of the OR versus its standard error. Additional sensitivity analyses were undertaken to evaluate the potential effect of key assumptions and study-level factors on the overall results. Meta-regression models were formed to explore potential heterogeneity as a result of potential risk factors or confounders on outcomes. A tria sequential analysis (TSA) was performed with the aim to maintain an over- all 5% risk of type I error, being the standard in most meta- analyses and systematic reviews.
  
  
  RESULTS
  58 articles reported combined stroke and mortality rates within 30 days of treatment. In the unselected overall meta-analysis, the incidence of stroke and death in the male and female groups differed significantly (Peto OR, 1,162; 95% CI, 1.067-1.266; P = .001), revealing a worse outcome for female patients. Moderate heterogeneity among the studies was identified (I(2) = 36%), and the possibility of publication bias was low (P = .03). In sensitivity analyses the meta-analysis of case series with gender aspects as a secondary outcome showed a significantly increased risk for 30-day stroke and death in women compared to men (Peto OR, 1.390; 95% CI, 1.148-1.684; P = .001), In contrast, meta-analysis of databases (Peto OR, 1.025; 95% CI, 0.958-1.097; P = .474) and case series with gender related outcomes as a primary aim (Peto OR, 1.202; 95% CI, 0.925-1.561; P = .168) demonstrated no increase in operative risk of stroke and death in women compared to men.
  
  
  CONCLUSIONS
  Meta-analyses of case series and databases dealing with CEA reveal inconsistent results regarding gender differences related to CEA-procedure and should not be transferred into clinical practice.
authors.affiliation: Department of Vascular and Endovascular Surgery, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germay. Thomas.luebke@uk-koeln.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Luebke
authors.affiliation: Department of Vascular and Endovascular Surgery, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germay. jan.brunkwall@uk-koeln.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Brunkwall
mesh_terms: D000367:Age Factors; D016893:Carotid Stenosis / Q000150:complications / Q000401:mortality* / Q000601:surgery*; D015897:Comorbidity; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D008297:Male; D011183:Postoperative Complications / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control; D012044:Regression Analysis; D012307:Risk Factors; D012737:Sex Factors; D020521:Stroke / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control; D016896:Treatment Outcome