Intra-Arterial Treatment For Stroke - A Year In Review And A Time For Change?

For years, Emergency Medicine has been at odds with Neurology's use of Intravenous Thrombolytics for management of acute stroke. This criticism was based on:  
- Multiple published negative trials, not demonstrating benefit and some showing harm.
- Neurology’s eagerness to use an industry sponsored, single “positive” study - the NINDS trial (published in 1995),
   as proof of benefit using IV thrombolytics for acute stroke. This was despite a reanalysis of the trial's raw data
   (obtained after a freedom-of-information claim by an American Emergency Physician - Jerome Hoffman),
   demonstrating significant flaws.

The use of CT-Perfusion imaging to guide therapeutic interventions (based on a vascular penumbra around the infarcted area), and the increasing use of Intra-Arterial Treatment for acute stroke, can probably now be considered evidence-based. 

Intra-arterial therapy can be broadly divided into: 
- Chemical dissolution of clots with locally delivered thrombolytic agents.
- Clot retrieval or thrombectomy with mechanical devices.

Four studies published over the last year have changed my opinion on the dreaded topic of “thrombolysis in stroke” (they can be downloaded below):

1. Published in January 2015, the MR CLEAN study (n=500, in the Netherlands) demonstrated that:
   - In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation.
   - Intra-arterial treatment administered within 6 hours after stroke onset was effective and safe.

2. The EXTEND-IA study, published in March 2015, was stopped early because of efficacy, after 70 patients had
   undergone randomisation: 
   - The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the
     endovascular-therapy group than in the alteplase-only group. 
   - The authors (including four from the MMC Stroke Unit) concluded that in patients with ischemic stroke with a
     proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging, early thrombectomy with
     the Solitaire FR stent retriever, as compared with alteplase alone, improved reperfusion, early neurologic  
     recovery, and functional outcome. (Funded by the Australian NHMRC).

3. November 2015, saw the publication of a meta-analysis of 8 randomised clinical trials (n=2423) of
   endovasculartherapy with mechanical thrombectomy vs standard medical care (which includes the use of tPA).
   The authors concluded that: 
   - Among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy was
     associated with improved functional outcomes and higher rates of angiographic revascularisation. 
   - There was no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.

4. A further analysis of data from MR CLEAN, published in December 2015, demonstrated that:
   - For every hour of reperfusion delay, the initially large benefit of intra-arterial treatment (IAT) decreases. 
   - The absolute risk difference for a good outcome was reduced by 6% per hour of delay. 
   - The authors conclude that patients with acute ischemic stroke require immediate diagnostic workup and IAT. 


With the increasing availability of CT-Perfusion to guide if and which therapy acute stroke patients receive, we have now probably moved beyond those initial disagreements. The role of Emergency Medicine in identifying acute stroke patients and facilitating rapid transfer to CT-Perfusion and interventional neuro-radiology, is pivotal. 

It is now time to work together with our neurology colleagues to ensure our acute stroke patients receive evidence based imaging and treatment, and achieve the best possible outcomes for a condition which would otherwise be devastating.

Will 2016 be The Year of the Stroke? 

Danny

Dr D. Ben-Eli, BSc, MD, FACEM
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