Ammad Mahmood, MBChB

Howard VJ, Algra A, Howard G, Bonati LH, de Borst GJ, Bulbulia R, Calvet D, Eckstein H-H, Fraedrich G, Greving JP, et al. Absence of Consistent Sex Differences in Outcomes From Symptomatic Carotid Endarterectomy and Stenting Randomized Trials. Stroke. 2021;52:416–423.

Management of carotid artery stenosis has been approached differently in women and men since the 1990s following the NASCET criteria.1 More recently, trials comparing carotid artery stenting with endarterectomy have shown the modification of treatment effect by sex to be variable. The Carotid Revascularisation Endarterectomy vs Stenting Trial (CREST)2 suggested women receiving stenting were at higher periprocedural risk of stroke, myocardial infarction or death compared to men, though there was no difference in the primary endpoint (periprocedural risks above or ipsilateral stroke within 4 years). Conversely, the International Carotid Stenting Study (ICSS)3 suggested a borderline higher periprocedural risk for men undergoing stenting. 

This meta-analysis pooled data from four trials of carotid artery stenting vs endarterectomy — CREST, ICSS, Endarterectomy versus Angioplasty in Patients with Symptomatic Severe Carotid Stenosis (EVA-3S)4 and Stent-Protected Angioplasty versus Carotid Endarterectomy in Symptomatic Patients (SPACE).5 A total of 4754 patients, 1437 women (30%), were included. The majority of events were periprocedural (335/433). Combining periprocedural risk and risk of ipsilateral stroke thereafter, the risk for women of stenting versus endarterectomy was found to be significantly lower in EVA-3S, non-significantly lower in ICSS and non-significantly higher in both SPACE and CREST. Overall, they found heterogeneity and inconsistency between trials, making the pooling of data inappropriate to draw conclusions from. Pooled data showed a trend to higher risk of stenting which did not reach significance in women but did in men, with no significant difference between women and men. Similar results were seen when considering periprocedural risk alone.

The authors concluded that the question about sex differences in risk of carotid stenting versus endarterectomy remain unanswered. Whilst pooled data suggested a higher periprocedural risk in both women and men with no significant modification of effect by sex alone, the authors rightly advised caution about interpretation of this given the divergent trial results.

This uncertainty is reflected in the AHA/ASA guidelines,6,7 which acknowledge the controversy regarding the influence of sex on patient selection for carotid intervention. Whilst this uncertainty remains, the selection of patients likely to benefit from carotid endarterectomy or stenting, particularly in women with moderate stenosis (50-69%), will remain a topic of debate.


1.           Barnett HJM, Taylor DW, Eliasziw M, et al. Benefit of Carotid Endarterectomy in Patients with Symptomatic Moderate or Severe Stenosis. New England Journal of Medicine 1998; 339(20): 1415-25.

2.           Howard VJ, Lutsep HL, Mackey A, et al. Influence of sex on outcomes of stenting versus endarterectomy: a subgroup analysis of the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST). The Lancet Neurology 2011; 10(6): 530-7.

3.           Bonati LH, Dobson J, Featherstone RL, et al. Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial. Lancet 2015; 385(9967): 529-38.

4.           Mas J-L, Chatellier G, Beyssen B, et al. Endarterectomy versus Stenting in Patients with Symptomatic Severe Carotid Stenosis. New England Journal of Medicine 2006; 355(16): 1660-71.

5.           Eckstein HH, Ringleb P, Allenberg JR, et al. Results of the Stent-Protected Angioplasty versus Carotid Endarterectomy (SPACE) study to treat symptomatic stenoses at 2 years: a multinational, prospective, randomised trial. The Lancet Neurology 2008; 7(10): 893-902.

6.           Kernan WN, Ovbiagele B, Black HR, et al. Guidelines for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack. Stroke 2014; 45(7): 2160-236.

7.           Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2019; 50(12): e344-e418.