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ω-3脂肪酸乙酯预处理及持续使用可减少颈动脉支架置入患者的慢血流现象并预防支架内再狭窄。

Pretreatment with and ongoing use of omega-3 fatty acid ethyl esters reduce the slow-flow phenomenon and prevent in-stent restenosis in patients undergoing carotid artery stenting.

作者信息

Nakagawa Ichiro, Park Hun Soo, Yokoyama Shohei, Wada Takeshi, Yamada Syuichi, Motoyama Yasushi, Kichikawa Kimihiko, Nakase Hiroyuki

机构信息

Department of Neurosurgery, Nara Medical University, Nara, Japan.

Department of Neurosurgery, Nara Medical University, Nara, Japan.

出版信息

J Vasc Surg. 2017 Jul;66(1):122-129. doi: 10.1016/j.jvs.2016.12.132. Epub 2017 Mar 27.

Abstract

OBJECTIVE

Carotid artery stenting (CAS) is a less invasive alternative to carotid endarterectomy, but it is essential to prevent thromboembolic complications during CAS and to suppress in-stent restenosis (ISR) after CAS because of the relatively high risk of periprocedural and follow-up stroke events. Clinical trials have demonstrated the strong relationship of carotid plaque vulnerability with the subsequent risk of ipsilateral ischemic stroke and thromboembolic complications during CAS. Recent studies demonstrated that both low eicosapentaenoic acid (EPA) and low docosahexaenoic acid (DHA) levels were significantly associated with lipid-rich coronary and carotid plaques, but little is known about the effect of administration of omega-3 fatty acids (O-3FAs) containing EPA and DHA before and after CAS for stabilizing carotid plaque, preventing thromboembolic complications, and suppressing ISR. In this study, the efficacy of pretreatment with and ongoing daily use of O-3FA in addition to statin treatment was evaluated in patients undergoing CAS.

METHODS

This study was a nonrandomized prospective trial with retrospective analysis of historical control data. From 2012 to 2015, there were 100 consecutive patients with hyperlipidemia undergoing CAS for carotid artery stenosis who were divided into two groups. Between 2012 and 2013 (control period), 47 patients were treated with standard statin therapy. Between 2014 and 2015 (O-3FA period), patients were treated with statin therapy and add-on oral O-3FA ethyl esters containing 750 mg/d DHA and 1860 mg/d EPA from 4 weeks before CAS, followed by ongoing daily use for at least 12 months. In all patients, the plaque morphology by virtual histology intravascular ultrasound, the incidence of new ipsilateral ischemic lesions on the day after CAS, the slow-flow phenomenon during CAS, and ISR within 12 months after CAS were compared between the periods.

RESULTS

The slow-flow phenomenon during CAS with filter-type embolic protection devices decreased in the O-3FA period (1 of 53 patients [2%]) compared with the control period (7 of 47 patients [15%]; P = .02). Furthermore, ISR for 12 months after CAS was significantly decreased in the O-3FA period (1 of 53 patients [2%]) compared with the control period (10 of 47 patients [21%]; P = .01). On virtual histology intravascular ultrasound analysis, the fibrofatty area was significantly smaller and the fibrous area was significantly greater in the O-3FA period. On multivariate logistic regression analysis, a low EPA/arachidonic acid ratio and a symptomatic lesion were the factors related to vulnerable plaque (P = .01 [odds ratio, 5.24; 95% confidence interval, 1.65-16.63] and P = .01 [odds ratio, 11.72; 95% confidence interval, 2.93-46.86], respectively).

CONCLUSIONS

Pretreatment with O-3FA reduces the slow-flow phenomenon generated by plaque vulnerability during CAS, and on-going daily use of O-3FA suppresses ISR after CAS.

摘要

目的

颈动脉支架置入术(CAS)是一种侵入性较小的替代颈动脉内膜切除术的方法,但在CAS期间预防血栓栓塞并发症以及抑制CAS后的支架内再狭窄(ISR)至关重要,因为围手术期和随访期发生卒中事件的风险相对较高。临床试验已证明颈动脉斑块易损性与同侧缺血性卒中及CAS期间血栓栓塞并发症的后续风险密切相关。最近的研究表明,二十碳五烯酸(EPA)水平低和二十二碳六烯酸(DHA)水平低均与富含脂质的冠状动脉和颈动脉斑块显著相关,但关于在CAS前后给予含EPA和DHA的ω-3脂肪酸(O-3FAs)对稳定颈动脉斑块、预防血栓栓塞并发症及抑制ISR的作用知之甚少。在本研究中,对接受CAS的患者评估了除他汀类治疗外,术前使用和持续每日使用O-3FA的疗效。

方法

本研究是一项非随机前瞻性试验,并对历史对照数据进行回顾性分析。2012年至2015年,连续100例因颈动脉狭窄接受CAS的高脂血症患者被分为两组。在2012年至2013年(对照期),47例患者接受标准他汀类治疗。在2014年至2015年(O-3FA期),患者在CAS前4周开始接受他汀类治疗并加用口服含750mg/d DHA和1860mg/d EPA的O-3FA乙酯,随后持续每日使用至少12个月。比较两个时期所有患者通过虚拟组织学血管内超声检查的斑块形态、CAS后次日新的同侧缺血性病变发生率、CAS期间的慢血流现象以及CAS后12个月内的ISR。

结果

与对照期(47例患者中有7例[15%])相比,O-3FA期使用滤器型栓子保护装置时CAS期间的慢血流现象减少(53例患者中有1例[2%];P = 0.02)。此外,与对照期(47例患者中有10例[21%])相比,O-3FA期CAS后12个月的ISR显著降低(53例患者中有1例[2%];P = 0.01)。在虚拟组织学血管内超声分析中,O-3FA期纤维脂肪面积显著减小,纤维面积显著增大。多因素逻辑回归分析显示,低EPA/花生四烯酸比值和有症状病变是与易损斑块相关的因素(分别为P = 0.01[比值比,5.24;95%置信区间,1.65 - 16.63]和P = 0.01[比值比,11.72;95%置信区间,2.93 - 46.86])。

结论

术前使用O-3FA可减少CAS期间由斑块易损性产生的慢血流现象,持续每日使用O-3FA可抑制CAS后的ISR。

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