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.

Fig. 1

Literature search strategy. Flow chart showing the strategy used for the literature search

Fig. 2

Forrest plot for carotid endarterectomy and stroke and death rates subjected to the gender. The odds for stroke and death within 30 days of CEA for females versus males. P is the statistical significance of the pooled Peto odds ratio. The size of the data marker indicates the weight of each trial. OR, odds ratio

Fig. 3

Forrest plot for carotid endarterectomy and stroke rates subjected to the gender. The odds for stroke within 30 days of CEA for females versus males. P is the statistical significance of the pooled Peto odds ratio. The size of the data marker indicates the weight of each trial. OR, odds ratio

Fig. 4

Scatterplot of the relationship between year of publication and Log Odds Ratio for stroke and death. Scatterplot shows the relationship between year of publication and log odds ratio for stroke and mortality

Fig. 5

Trial sequential analysis of the effects of carotid endarterectomy on periprocedural stroke and death subjected to the gender and publication date after the year 2004

Fig. 6

Trial sequential analysis of the effects of carotid endarterectomy on periprocedural stroke and death subjected to the gender and type of study (outcome of interest as primary aim)

Fig. 7

Trial sequential analysis of the effects of carotid endarterectomy on periprocedural stroke and death subjected to the gender and type of study (outcome of interest as secondary aim)