Critical Care, Critical Care Alert

Critical Care Alert: Endovascular Therapy Option for Late Presenting Ischemic Stroke Patients

Critical Care Alert

Albers GW, et al, for the DEFUSE 3 Investigators*. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion ImagingN Engl J Med. 2018;378:708-718.

Nogueira RG, et al, for the DAWN Trial Investigators*. Thrombectomy 6 to 24 Hours After Stroke with a Mismatch Between Deficit and Infarct. N Engl J Med. 2018;378:11-21.

At 11 am, EMS brings in a 76-year-old female with history of HF, CAD, HTN, DM, atrial fibrillation on warfarin, and Wegener's granulomatosis. She was reportedly last seen normal by family at 2100 last night and is usually A&O x 3 at baseline, but family called EMS reporting altered mental status when they checked on her just PTA. You help the nurses place the patient on the monitor and notice she is in atrial fibrillation with RVR, with HR 130-140BPM, BP 160/100, RR 25, SPO2 97% on 4L NC with bedside blood sugar of 203. On exam, she is awake and is moving her Left side, with no purposeful movements of her right side, and she is not following commands. She is taken for CTH which shows no ICH but age-indeterminate infarct of the left basal ganglia. CTA shows occlusion of proximal M1 of LT MCA.

Ischemic stroke is one of the most common causes of death and devastating permanent disability worldwide. Current standard care for stroke consists of giving thrombolytic up to 3-4.5 hours in select patients. Administration of thrombolytics in stroke patients is associated with risk of ICH. NINDS data from 1997 as well as more recent meta-analysis findings have shown an approximately 6% risk of symptomatic ICH when tPA is given within the 3-hour window. With the evolution of neuroradiology, multiple recent trials have shown the potential benefit of mechanical thrombectomy for select patient groups whether or not they also received systemic thrombolytics. Prior to the recent DAWN and DEFUSE 3 trials detailed below, mechanical thrombectomy was limited to those presenting with large artery occlusion within 6 hours of symptom onset. The newest evidence from these two trials suggests benefit to endovascular therapy in patients presenting up to 16 and 24 hours after their symptom manifestation.

DAWN Trial

DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake up and Late Presenting Strokes Undergoing Neuro Intervention with Trevo



Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke


In patients with ischemic strokes last known to be well between 6 to 24 hours prior to hospital arrival with mismatch between clinical deficit and infarction, are outcomes for disability at 90 days as judged by the modified Rankin Score, better for treatment with thrombectomy and standard care or for standard care alone?


Does endovascular thrombectomy for ischemic stroke cases as identified by perfusion imaging 6-16 hours after last seen normal offer better functional outcomes as defined by the Rankin Scoring system than standard medical therapy alone?

(More specifically in patients with proximal MCA or internal carotid artery occlusions and ischemic but not infarcted tissue) 



Multicenters (26 centers throughout the U.S., Canada, Australia, Europe)
     All centers annually perform at least 40
     mechanical thrombectomy cases

Open Labeled
Blind Assessment to End Points



Multicenter (38 U.S. hospitals)
Blinded to Outcome Assessment
Open Label (no placebo)


206 patients

  • Age 55-83 y/o
  • Median NIHSS 17
  • 107 treated with thrombectomy and    medical management
  • 99 treated with medical management alone (control)


182 patients

  • Age 59-80
  • Median NIHSS 16
  • 92 to endovascular therapy and medical management
  • 90 to standard medical therapy alone


  • Age > 18 y/o
  • No ICH
  • Last known to be well 6-24 hours PTA
  • Infarct < 1/3 the MCA territory
  • Occlusion located within the intracranial internal carotid a. or the M1 segment of the MCA
  • Mismatch between severity of clinical deficit and infarct volume


  • Ischemic stroke within 6-16 hours of last seen normal
  • Location in MCA or intracranial or cervical internal carotid artery
  • Tissue not infarcted
  • Infarct size < 70mL
    *equivalent to <1/3 MCA territory as required by the DAWN trial
  • Penumbra > 15mL
  • Ratio of ischemic volume: infarct volume >/= 1.8




Thrombectomy and Medical Management

Medical Management (Control)

Mean Disability Score at 90 days



Functional Independence at 90 days



- Mean Disability Score assessed by utility weighted modified Rankin in which 0=death and 10=no symptoms/no disability

- Functional Independence is defined as a Modified Rankin Scale score of 0, 1, or 2

- Modified Rankin Scale measures the disability and/or the dependence of stroke patients on assistance with activities of daily living, please see attached chart for reference





Thrombectomy and Medical Management

Medical Management (Control)

Modified Rankin at 90 days

Median of 3

IQR of 1-4

Median of 4

IQR of 3-6




Thrombectomy and Medical Management

Medical Management (Control)

Early Response



Recanalization at 24 hours



Change from median baseline infarct volume at 24 hours on CTA/MRA



Infarct volume at 24 hours



- Early Response was defined as a decrease in NIHSS by >/= 10 from baseline OR NIHSS of 0 or 1 on day 5,6,7 of hospitalization or at discharge if occured before day 5



Thrombectomy and Medical Management

Medical Management (Control)

Functional Independence at 90 days



Mortality at 90 days



Symptomatic ICH within 36 hours*



Serious Adverse Effects



- Functional Independence as defined above in the DAWN trial using the Modified Rankin Scale with scores of 0, 1, or 2

- Symptomatic ICH defined as NIHSS increasing by >/= 4 points from baseline over 36 hours

*Difference was not statistically significant

Safety Outcomes


Thrombectomy and Medical Management

Medical Management (Control)

Stroke Related death at 90 days



Death from any cause at 90 days



Symptomatic ICH



Neurological Deterioration



- Symptomatic ICH is the presence of extravascular blood in the cranium causing increase in NIHSS >/= 4 or death and deemed to be predominant cause of deterioration

- Neurological deterioration as an increase in NIHSS of >/=4 points within 5 days and not attributable to edema or hemorrhage

Imaging Outcomes


Thrombectomy and Medical Management

Medical Management (Control)

Infarct Volume at 24 hours



Lesion Growth at 24 hours



Reperfusion of >90% at 24 hours



Complete Recanalization



EFFICACY as by Thrombolysis in Cerebral Infarction (TICI) Assessment

  • 57% of patients achieved a score of 2b with 50% to 90% reperfusion
  • 19% of patients achieved a score of 3 with complete reperfusion


At 31 months into the DAWN trial, enrollment was stopped when the interim analysis showed a predictive probability of 95% for superiority for thrombectomy regarding mean disability at 90 days after intervention. Similarly, enrollment in the DEFUSE 3 Trial was also stopped at its interim analysis due to statistically significant results in favor of treatment with thrombectomy and standard medical therapy.

Prior to the DAWN and DEFUSE 3 trials, studies had shown that benefits associated with endovascular thrombectomy diminished as the time from stroke onset to intervention increased beyond the 6-hour window. However, these two studies concluded that thrombectomy performed as far as 6 to 16 and even 24 hours, as concluded by the DAWN trial, has better functional outcomes than standard medical therapy alone does. The main difference between these two studies, was the inclusion of patients with a penumbra in the DEFUSE 3 trial. This requirement allowed for selection of patients with a slower growing infarct likely due to better collateral circulation. Both trials used the same automated software to measure the volume of infarct. Whereas the DAWN trial selected for patients with a discrepancy between the severity of the clinical deficit and the infarct size, the DEFUSE 3 trial included a broader patient population by enrolling patients with milder stroke symptoms and larger core infarcts. Regardless, both studies resulted in less disability and higher functional independence when thrombectomy plus standard medical therapy were used versus standard therapy alone.

With research favoring the utility and extension of the thrombectomy window, many questions will arise regarding the management of late presenting stroke cases. It is unclear how broad the actual benefit of these findings can be applied clinical practice. We need to pay close attention to the specific criteria of patient selection. Available collateral circulation is the key for success in applying endovascular therapy in late presenting stroke cases. Frequent repeating of neuro exam is crucial as an indicator of available collateral circulation to guide intervention considerations.

Modified Rankin Scoring System

*Of note, this differs from the utility-weighted scoring system used in the DAWN trial



No symptoms


No Significant Disability

Despite mild symptoms, able to independently carry out daily activities


Slight Disability

Can look after their own affairs but limited in ability to carry out all prior activities


Moderate Disability

Can walk unassisted but assistance required for other activities


Moderately Severe

Unable to attend to own bodily functions and unable to walk unassisted


Severe Disability

Require around the clock nursing care, bedridden and incontinent




Related Articles

Critical Care Device Series: Transvenous Pacemaker

Temporary transvenous pacing (TTVP) utilizes central venous access to pass an electrode into the right ventricle. TTVPs are one of the most infrequently performed procedures by emergency physicians;

Aortic Occlusion: A Rare Presentation of Back Pain

Back pain is a common chief complaint in the emergency department. However, not all back pain is simple lumbago, and as emergency physicians, it is crucial to be aware of more insidious causes of back