Sex differences in Outcome after Carotid Revascularization in Symptomatic and Asymptomatic Carotid Artery Stenosis

Objective: Sex differences regarding the safety and efficacy of carotid revascularization in carotid artery stenosis have been addressed in several studies with conflicting results. Moreover, women are underrepresented in clinical trials leading to limited conclusions regarding the safety and efficacy of acute stroke treatments. Methods: A systematic review and meta-analysis was performed by literature search including 4 databases from January 1985 to December 2021. Sex differences in the efficacy and safety of revascularization procedures, including carotid endarterectomy (CEA) and carotid artery stenting (CAS), for symptomatic and asymptomatic carotid artery stenoses were analyzed. Results: Regarding carotid endarterectomy (CEA) in symptomatic carotid artery stenosis, the stroke risk in men (3.6%) and women (3.9%) based on 99,495 patients (30 studies) did not differ (p=0.16). There was also no difference in the stroke risk by different time frames up to 10 years. Compared with men, women treated with CEA had a significantly higher stroke or death rate at 4 months (2 studies, 2565; 7.2% vs 5.0%; OR 1.49, 95% CI 1.04-2.12; I2=0%; p=0.03), and a significantly higher rate of restenosis (1 study, 615; 17.2% vs. 6.7%; OR 2.81,95% CI 1.66-4.75; p=0.0001). For carotid stenting (CAS) in symptomatic artery stenosis data showed a non-significant tendency toward higher peri-procedural stroke in women. Whereas, for asymptomatic carotid artery stenosis, data based on 332,344 patients showed that women compared to men after CEA had similar rates of stroke, stroke or death and the composite outcome stroke/death/myocardial infarction. The rate of restenosis at 1 year was significantly higher in women compared to men (1 study, 372 patients; 10.8% vs 3.2%; OR 3.71, 95% CI 1.49-9.2; p=0.005). Furthermore, carotid stenting in asymptomatic patients was associated with low risk of a postprocedural stroke in both sexes, but a significantly higher risk of in-hospital myocardial infarction in women than men (8445 patients, 1.2% vs. 0.6%, OR 2.01, 95%CI 1.23-3.28, I2=0%, p=0.005). Conclusions: A few sex-differences in short term outcomes after carotid revascularization for symptomatic and asymptomatic carotid artery stenosis were found, although there were no significant differences in the overall stroke. This indicates a need for larger multicenter prospective studies to evaluate these sex-specific differences. More women, including those aged over 80 years, need to be enrolled in RCTs, to better understand if sex differences exist and to tailor carotid revascularization accordingly.