Department of Vascular Surgery, the Permanente Medical Group, South San Francisco, CA; Division of Research, Kaiser Permanente Northern California, Oakland, CA.
Division of Research, Kaiser Permanente Northern California, Oakland, CA.
J Vasc Surg. 2023 Nov;78(5):1239-1247.e4. doi: 10.1016/j.jvs.2023.06.024. Epub 2023 Jul 4.
The results of current prospective trials comparing the effectiveness of carotid endarterectomy (CEA) vs standard medical therapy for long-term stroke prevention in patients with asymptomatic carotid stenosis (ACS) will not be available for several years. In this study, we compared the observed effectiveness of CEA and standard medical therapy vs standard medical therapy alone to prevent ipsilateral stroke in a contemporary cohort of patients with ACS.
This cohort study was conducted in a large integrated health system in adult subjects with 70% to 99% ACS (no neurologic symptom within 6 months) with no prior ipsilateral carotid artery intervention. Causal inference methods were used to emulate a conceptual randomized trial using data from January 1, 2008, through December 31, 2017, for comparing the event-free survival over 96 months between two treatment strategies: (1) CEA within 12 months from cohort entry vs (2) no CEA (standard medical therapy alone). To account for both baseline and time-dependent confounding, inverse probability weighting estimation was used to derive adjusted hazard ratios, and cumulative risk differences were assessed based on two logistic marginal structural models for counterfactual hazards. Propensity scores were data-adaptively estimated using super learning. The primary outcome was ipsilateral anterior ischemic stroke.
The cohort included 3824 eligible patients with ACS (mean age: 73.7 years, 57.9% male, 12.3% active smokers), of whom 1467 underwent CEA in the first year, whereas 2297 never underwent CEA. The median follow-up was 68 months. A total of 1760 participants (46%) died, 445 (12%) were lost to follow-up, and 158 (4%) experienced ipsilateral stroke. The cumulative risk differences for each year of follow-up showed a protective effect of CEA starting in year 2 (risk difference = 1.1%, 95% confidence interval: 0.5%-1.6%) and persisting to year 8 (2.6%, 95% confidence interval: 0.3%-4.8%) compared with patients not receiving CEA.
In this contemporary cohort study of patients with ACS using rigorous analytic methodology, CEA appears to have a small but statistically significant effect on stroke prevention out to 8 years. Further study is needed to appropriately select the subset of patients most likely to benefit from intervention.
目前比较无症状颈动脉狭窄（ACS）患者颈动脉内膜切除术（CEA）与标准药物治疗长期预防卒中效果的前瞻性试验结果还需要数年时间。本研究旨在比较当代 ACS 患者队列中 CEA 联合标准药物治疗与单纯标准药物治疗预防同侧卒中的效果。
这项队列研究在一个大型综合医疗系统中进行，纳入了 70%至 99% ACS（6 个月内无神经症状）且无同侧颈动脉动脉干预史的成年患者。采用因果推理方法，利用 2008 年 1 月 1 日至 2017 年 12 月 31 日的数据，模拟了一个概念性随机试验，比较两种治疗策略（1）CEA 治疗组（从入组队列开始的 12 个月内进行 CEA）与（2）非 CEA 治疗组（单纯标准药物治疗）在 96 个月时的无事件生存率。为了同时考虑基线和时间依赖性混杂因素，采用逆概率加权估计法得出校正后的风险比，基于两种逻辑边缘结构模型评估反事实风险的累积风险差异。使用超级学习法自适应估计倾向评分。主要结局为同侧前循环缺血性卒中。
该队列纳入了 3824 例 ACS 患者（平均年龄 73.7 岁，57.9%为男性，12.3%为现吸烟患者），其中 1467 例患者在第 1 年内接受了 CEA，而 2297 例患者从未接受过 CEA。中位随访时间为 68 个月。共有 1760 例患者（46%）死亡，445 例（12%）失访，158 例（4%）发生同侧卒中。每年随访的累积风险差异显示，与未接受 CEA 的患者相比，CEA 在第 2 年（风险差异=1.1%，95%置信区间：0.5%-1.6%）开始具有保护作用，一直持续到第 8 年（2.6%，95%置信区间：0.3%-4.8%）。
本研究采用严格的分析方法，对 ACS 患者进行了一项当代队列研究，结果显示 CEA 在 8 年内对预防卒中有一定的但具有统计学意义的效果。需要进一步的研究来确定最有可能从干预中获益的患者亚组。
