Sex is a critical factor in the timing of surgical intervention in men and women with severe carotid artery disease: Protocol for a systematic review and meta-analysis

Stroke is a leading cause of mortality worldwide among men and women. Sex differences exist in stroke incidence, mortality, long-term functional outcomes, and treatment responses. Timing of carotid surgical intervention is essential in the prevention of strokes, particularly among women. However, it remains unclear whether sex is a critical factor that influences surgical wait times. In this protocol we outlined a systematic review and meta-analysis regarding sex differences in the timing of surgical intervention among men and women with severe carotid artery disease, as well as secondary analyses assessing the impact of delayed intervention on perioperative and postoperative clinical outcomes. Various electronic databases will be searched: Medline, Embase, The Cochrane Library, PubMed, CINAHLPlus, Scopus, grey literature, and trial registries. Search strategies will be designed to identify human (>=18 years) controlled trials, cohort studies, case-control studies, and cross-sectional studies concerning “sex differences in the timing of surgical intervention in men and women with severe carotid artery disease.”Apreliminary search strategy was developed for Medline (1946 to August 3rd, 2020). For primary outcomes, data must involve timing spanning from symptom onset to surgical intervention in symptomatic individuals, or timing spanning from first medical contact to surgical intervention in asymptomatic individuals. Secondary outcomes include effect estimates for peri-operative and post-operative cardiovascular (including cerebrovascular) morbidity and mortality, based on timing of intervention. Pooled analyses will be conducted using the random-effects model. Publication bias will be assessed by visual inspection of funnel plots and by Begg’s and Egger’s statistical tests. Between-studies heterogeneity will be measured using the I2 test (P<0.10). Sources of heterogeneity will be explored by sensitivity, subgroup, and meta-regression analyses. Findings will be shared through scientific conferences and societies, social media, and consumer advocacy groups. Results will be used to inform current guidelines for carotid disease management and stroke prevention in men and women.