Department of Epidemiology (V.J.H.), School of Public Health, University of Alabama at Birmingham.
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus and Julius Center for Health Sciences and Primary Care (A.A.), and Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands.
Stroke. 2021 Jan;52(2):416-423. doi: 10.1161/STROKEAHA.120.030184. Epub 2021 Jan 25.
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 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.
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 ≤0.10.
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 (=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.
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).
CREST（颈动脉血管重建内膜切除术与支架置入试验）报道称，随机接受颈动脉支架置入术（CAS）治疗的女性患者围手术期任何卒中、死亡或心肌梗死的风险高于随机接受颈动脉内膜切除术（CEA）治疗的女性患者。在 4 年的主要结局中，未发现女性患者相对于男性患者在治疗风险上存在差异。我们旨在对大型随机试验中的有症状患者进行汇总分析，以便在围手术期 120 天内以及之后同侧卒中期间提供更精确的 CAS 与 CEA 风险的性别差异估计值。
Carotid Stenosis Trialists' Collaboration 的数据包括 EVA-3S（有症状的严重颈动脉狭窄患者内膜切除术与血管成形术比较试验）、SPACE（有症状患者支架保护血管成形术与颈动脉内膜切除术比较试验）、ICSS（国际颈动脉支架置入研究）和 CREST 中症状性患者的结局。主要结局是随机分组后 120 天内的任何卒中和死亡以及此后同侧卒中。使用泊松回归估计事件发生率和相对风险；采用治疗-性别-试验交互项评估性别对治疗效果的影响修饰，具有统计学意义的交互作用预先定义为≤0.10。
在中位 2.7 年的随访期间，3317 名男性和 1437 名女性中发生了 433 例主要结局事件。1 项试验中，女性患者的 CAS 与 CEA 主要结局的相对风险明显低于男性患者，另 1 项试验中则名义上较低，而在另外两项试验中则名义上较高。治疗-性别-试验交互项有统计学意义（=0.065），表明试验之间存在异质性。这种异质性的主要原因是围手术期的差异。尽管如此，当将这些试验汇总时，在任何随访期间都没有发现风险的显著性别差异。
不同试验中治疗效果（CAS 与 CEA 的相对风险）的性别差异的大小存在显著差异，表明从这些试验中汇总数据来估计性别差异可能是无效的。在有症状的患者中，性别是否作为 CAS 与 CEA 治疗效果的效应修饰因子仍然不确定。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT00190398（EVA-3S）和 NCT00004732（CREST）。网址：https://www.isrctn.com；唯一标识符：ISRCTN57874028（SPACE）和 ISRCTN25337470（ICSS）。
