EBM Consult

Acute Ischemic Stroke: The Role for Endovascular Therapy

Take Home Points:

  • Endovascular therapy, as an adjunct to standard stroke therapy, may be beneficial for a very select population of patients that present with an acute ischemic stroke and have a proven large, proximal occlusion on imaging.
    • Endovascular therapy includes any one or more of the following:
      • Intra-arterial thrombolytic therapy
      • Clot and stent retrieval
      • Thrombectomy with mechanical devices
  • Endovascular therapy should be considered in patients with a clinical stroke who fulfill the following criteria:                 
    • Age ≥ 18 years
    • National Institute of Health Stroke Scale (NIHSS) ≥ 6
    • Have received intravenous tissue plasminogen activator (IV tPA), alteplase (Activase) within 4.5 hours of onset of symptoms
    • Have a demonstrated large, proximal (middle cerebral artery, internal carotid artery, or anterior cerebral artery) occlusion on imaging
    • Are eligible to receive endovascular therapy within 6 hours of a clinical stroke


The administration of IV tPA, specifically alteplase (Activase), is currently the only FDA-approved treatment for acute ischemic stroke. While tPA is considered the Gold Standard therapy for acute stroke care, its use is limited by:

  • Multiple contraindications
  • Narrow therapeutic time window (up to 4.5 hours for some eligible patients)
  • Reduced efficacy with large clot burden or proximal occlusions of the major intracranial arteries. 

Alternative interventions to IV tPA include:

  • Intra-arterial thrombolytic therapy
  • Endovascular (intra-arterial) thrombectomy
  • Endovascular (intra-arterial) thromboaspiration

Despite previous large, randomized controlled trials using first generation endovascular devices (MR RESCUE, IMS III, SYNTHESIS EXPANSION) suggesting no large magnitude benefit and even potential harm with endovascular therapy, critical reviews of these trials have suggested that a possible benefit may exist in a more select patient population using latest generation endovascular devices.

Several subsequent randomized controlled trials (MR CLEAN, EXTEND-IA, ESCAPE) investigated endovascular intervention a smaller subset of acute ischemic stroke patients, including only those with large proximal occlusions confirmed by neuroimaging. The percentage of patients independent at 90 days (modified Rankin score of 0-2) in control (usual care) and  intervention (usual care plus endovascular therapy) groups was compared. Key findings of these studies include:

  • Dramatic improvements in neurologic outcomes in favor of intra-arterial intervention following standard stroke care with IV tPA.
  • Demonstration of a 14% (MR CLEAN), 33% (EXTEND-IA), and 24% (ESCAPE) absolute benefit in independence at 90 days.
  • Mortality benefit noted in one trial (7% absolute benefit, ESCAPE trial)

Other observations from this literature:

  • All three trials included only patients with proven large, proximal occlusions on imaging, and two trials (EXTEND-IA, ESCAPE) additionally required imaging-based evidence of salvageable tissue as identified by an ischemic penumbra, further narrowing the select group of patients to which these results apply, and who are likely to benefit from thrombolytic therapy based on current data.
  • EXTEND-IA and ESCAPE were terminated early based on highly positive interim efficacy analysis, which was conducted after the MR CLEAN trial was published reporting an absolute benefit of endovascular therapy.
  • Almost all patients enrolled in the intervention groups of these trials received IV tPA prior to endovascular intervention. Those that did not receive IV tPA prior to endovascular intervention were too few to allow for extrapolation of significant results.
  • While intra-arterial therapy was defined as either intra-arterial tPA or mechanical intervention in some of these trials, the vast majority of patients underwent mechanical intervention with latest generation retrievable stents and interpretations of patient outcomes should consider this.
  • Two additional studies (REVASCAT, SWIFT) further upheld the reported benefit of intra-arterial interventions in conjunction with the standard of care for acute stroke patients with equally dramatic results. Both of these trials were also stopped early.


  • While three initial trials of endovascular therapy for acute CVA that utilized first generation endovascular devices in patients that had also received IV-tPA reported neutral to negative outcomes, subsequent trials (MR CLEAN, EXTEND-IA, ESCAPE) that carefully selected patients with large, proximal occlusions and evidence of salvageable brain tissue and used newer generation retrievable stents almost exclusively reported improved reperfusion rates and positive neurologic outcomes.
  • Current evidence suggests that in tPA eligible patients presenting with an acute ischemic event and a proven large proximal arterial occlusion on imaging, endovascular therapy following IV tPA administration in this very select patient population may have a significant morbidity benefit and a possible mortality benefit.
  • It is important to note that the results of these trials (MR CLEAN, EXTEND-IA, ESCAPE) should not be generalized beyond their strict inclusion criteria, as potential harm has been reported with endovascular interventions for less select patient populations.

  Karolina DeAugustinis, MD
  Anthony J. Busti, MD, PharmD, FNLA, FAHA;  Jeremiah Hinson, MD, PhD
Last Reviewed:
  August 2015

Supporting Guidelines

  • American Stroke Association (2015)

    • Patients eligible for intravenous r-tPA should receive intravenous r-tPA even if endovascular treatments are being considered.
    • Patients should receive endovascular therapy with a stent retriever if they meet all the following criteria.
      • Prestroke modified Rankin Scale score 0 to 1
      • Acute ischemic stroke receiving intravenous r-tPA within 4.5 hours of onset according to guidelines from professional medical societies
      • Causative occlusion of the internal carotid artery or proximal MCA (M1)
      • Age ≥18 years
      • NIHSS score of ≥6
      • Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of ≥6
      • Treatment can be initiated (groin puncture) within 6 hours of symptom onset
    • Guideline Rating:  Class I; Level of Evidence A
    • Reference:2015 AHA/ASA Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015 Jun 29. [Epub ahead of print]  PubMed

Original Studies

  • Berkhemer et al (MR CLEAN investigators). A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. PubMed
  • Campbell et al (EXTEND-IA Investigators). Endovascular Therapy for Ischemic Stroke with Perfusion-Imaging Selection. N Engl J Med 2015 Mar 12;372(11):1009-18. PubMed
  • Goyal et al (ESCAPE Trial investigators). Randomized Assessment of Rapid Endovascular Treatment of Ischemic Stroke. N Engl J Med 2015 Mar 12;372(11):1019-30. PubMed

Related Articles

  • Kidwell et al (MR RESCUE Investigators). A trial of imaging selection and endovascular treatment for ischemic stroke. N Engl J Med 2013 Mar 7;368(10):914-23.PubMed
  • Broderick et al (IMS-III Investigators). Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 2013 Mar 7;368(10):893-903. PubMed

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  • Intra-arterial Therapy, Intraarterial Therapy, Acute Stroke Endovascular Therapy, Endovascular Treatment Acute Stroke, tPA Acute Stroke