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

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


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.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angioplasty / adverse effects
  • Angioplasty / instrumentation*
  • Biomarkers / blood
  • Coronary Circulation / drug effects*
  • Coronary Stenosis / complications
  • Coronary Stenosis / diagnostic imaging
  • Coronary Stenosis / therapy*
  • Docosahexaenoic Acids / administration & dosage*
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Therapy, Combination
  • Eicosapentaenoic Acid / administration & dosage*
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipidemias / blood
  • Hyperlipidemias / complications
  • Hyperlipidemias / diagnosis
  • Hyperlipidemias / drug therapy*
  • Lipids / blood
  • Male
  • Middle Aged
  • No-Reflow Phenomenon / diagnosis
  • No-Reflow Phenomenon / etiology
  • No-Reflow Phenomenon / physiopathology
  • No-Reflow Phenomenon / prevention & control*
  • Plaque, Atherosclerotic
  • Prospective Studies
  • Recurrence
  • Retrospective Studies
  • Risk Factors
  • Stents*
  • Time Factors
  • Treatment Outcome


  • Biomarkers
  • Drug Combinations
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid