Absence of Consistent Sex Differences in Outcomes From Symptomatic Carotid Endarterectomy and Stenting Randomized Trials
Carotid Stenosis Trialists’ Collaboration
(2021) Stroke, volume 52, issue 2, pp. 416 - 423
(Article)
Abstract
BACKGROUND AND PURPOSE: CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial) reported a higher periprocedural risk for any stroke, death, or myocardial infarction for women randomized to carotid artery stenting (CAS) compared with women randomized to carotid endarterectomy (CEA). No difference in risk by treatment was detected for women relative to
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men in the 4-year primary outcome. We aimed to conduct a pooled analysis among symptomatic patients in large randomized trials to provide more precise estimates of sex differences in the CAS-to-CEA risk for any stroke or death during the 120-day periprocedural period and ipsilateral stroke thereafter. METHODS: Data from the Carotid Stenosis Trialists' Collaboration included outcomes from symptomatic patients in EVA-3S (Endarterectomy Versus Angioplasty in Patients With Symptomatic Severe Carotid Stenosis), SPACE (Stent-Protected Angioplasty Versus Carotid Endarterectomy in Symptomatic Patients), ICSS (International Carotid Stenting Study), and CREST. The primary outcome was any stroke or death within 120 days after randomization and ipsilateral stroke thereafter. Event rates and relative risks were estimated using Poisson regression; effect modification by sex was assessed with a sex-by-treatment-by-trial interaction term, with significant interaction defined a priori as P≤0.10. RESULTS: Over a median 2.7 years of follow-up, 433 outcomes occurred in 3317 men and 1437 women. The CAS-to-CEA relative risk of the primary outcome was significantly lower for women compared with men in 1 trial, nominally lower in another, and nominally higher in the other two. The sex-by-treatment-by-trial interaction term was significant (P=0.065), indicating heterogeneity among trials. Contributors to this heterogeneity are primarily differences in periprocedural period. When the trials are nevertheless pooled, there were no significant sex differences in risk in any follow-up period. CONCLUSIONS: There were significant differences between trials in the magnitude of sex differences in treatment effect (CAS-to-CEA relative risk), indicating pooling data from these trials to estimate sex differences might not be valid. Whether sex is acting as an effect modifier of the CAS-to-CEA treatment effect in symptomatic patients remains uncertain. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00190398 (EVA-3S) and NCT00004732 (CREST). URL: https://www.isrctn.com; Unique identifier: ISRCTN57874028 (SPACE) and ISRCTN25337470 (ICSS).
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Keywords: carotid stenosis, endarterectomy, sex characteristics, stents, women, Clinical Neurology, Cardiology and Cardiovascular Medicine, Advanced and Specialised Nursing, Journal Article
ISSN: 0039-2499
Publisher: Lippincott Williams & Wilkins
Note: Funding Information: Dr de Borst has received an advisory board fee from Bayer. Dr Bonati has received an unrestricted research grant from AstraZeneca; consultancy or advisory board fees or speaker’s honoraria from Amgen, Bayer, Bristol-Myers Squibb, Claret Medical, and InnovHeart; and travel grants from AstraZeneca and Bayer. Dr Ringeleb has received advisory board fees or speaker’s honoraria from Bayer, Boehringer Ingelheim, Daiichi Sankyo, and Pfizer. The other authors report no conflicts. Funding Information: Dr Greving is supported by the Dutch Heart Foundation (grant No. 2013T128). The research of Dr Halliday is funded by the National Institute for Health Research, Oxford Biomedical Research Center. Dr Bonati received grants from the Swiss National Science Foundation (PBBSB-116873), the University of Basel, Switzerland, and the Stroke Association, United Kingdom. Dr Bulbulia received funding from the UK Medical Research Council. Dr Brown’s Chair in Stroke Medicine was supported by the Reta Lila Weston Trust for Medical Research. Part of this work was undertaken at University College London, which received a proportion of funding from the UK Department of Health National Institute for Health Research Biomedical Research Centres funding scheme. Dr Howard, G. Howard, and Dr Brott were funded by the National Institutes of Health/National Institute of Neurological Disorders and Stroke U01 NS038384. Publisher Copyright: © 2021 Lippincott Williams and Wilkins. All rights reserved.
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