Ischemic Stroke Treatment Archive

09 Nov
November 9, 2015

Ischemic Stroke Treatment ArchiveI recently returned from the American College of Emergency Physicians (ACEP) Conference which took place from Oct. 26th – 29th, 2015 in Boston, MA.  There were really a lot of amazing talks by so many amazing speakers but one lecture in particular by David Newman, of SMART EM and The NNT fame, made me realize that there is just so much research on treatment of ischemic stroke, that I can’t even keep them straight.  So what I thought I would do is create an archive of all that research and continue to add to the list as more research is released.  I don’t know about you, but I find myself spending lots of time looking this information up every time I need it. 

Systemic Lytic Therapy in the Treatment of Ischemic Stroke

TrialLead AuthorYear of StudyPatientsOutcome
MAST-IMulticentre Acute Stroke Trial - Italy (MAST-I) Group1995622No Benefit
ECASS-IHacke W1995620No Benefit
NINDS-1The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group1995291
No Benefit
NINDS-2The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group199533312% Disability Benefit
MAST-EMulticentre Acute Stroke Trial - Europe (MAST-E) Group1996310Stopped Early due to Increased Death by 9%
ASKDonnan GA1996340Stopped Early due to Increased Death by 16%
ECASS-IIHacke W1998308No Benefit
ATLANTIS-BClark WM1999547Stopped Early due to Increased Deaths by 14%
ATLANTIS-AClark WM2000142Stopped Early due to Increased Deaths by 16%
ECASS-IIIHacke W20088218% Disability Benefit
DIAS-2Hacke W2009186Stopped Early due to Increased Deaths by 16%
IST-3IST-3 Collaborative Group20123035No Benefit
DIAS-3Albers GW2012492No Benefit

What does the American College of Emergency Physicians (ACEP) 2015 Clinical Policy Say? [PDF HERE]

  1. Is IV tPA safe and effective for patients with acute ischemic stroke if given within 3 hours of symptom onset?
    • Level A recommendations: None specified.
    • Level B recommendations: With a goal to improve functional outcomes, IV tPA should be offered and may be given to selected patients with acute ischemic stroke within 3 hours after symptom onset at institutions where systems are in place to safely administer the medication. The increased risk of symptomatic intracerebral hemorrhage (sICH) should be considered when deciding whether to administer IV tPA to patients with acute ischemic stroke.
    • Level C recommendations: When feasible, shared decision making between the patient (and/or his or her surrogate) and a member of the health care team should include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke (Consensus recommendation).
  2. Is IV tPA safe and effective for patients with acute ischemic stroke treated between 3 to 4.5 hours after symptom onset?
    • Level A recommendations: None specified.
    • Level B recommendations: Despite the known risk of symptomatic intracerebral hemorrhage (sICH) and the variability in the degree of benefit in functional outcomes, IV tPA may be offered and may be given to carefully selected patients with acute ischemic stroke within 3 to 4.5 hours after symptom onset at institutions where systems are in place to safely administer the medication.
    • Level C recommendations: When feasible, shared decision making between the patient (and/or his or her surrogate) and a member of the health care team should include a discussion of potential benefits and harms prior to the decision whether to administer IV tPA for acute ischemic stroke (Consensus recommendation).

Endovascular Treatment of Ischemic Stroke

Trial NameLead AuthorYear of StudyPatientsOutcome
IMS-IIIBroderick JP2013656No Benefit
MR RESCUEKidwell CS2013118No Benefit
SYNTHESISCiccone A2013181No Benefit
MR CLEANFransen PS201450013.5% Disability Benefit
ESCAPEGoyal M201531624% Disability Benefit
EXTEND IACampbell BC20157031% Disability Benefit
SWIFT PRIMESaver JL201519626% Disability Benefit
REVASCATJovin TG201520616% Disability Benefit

What should we take away from the above endovascular studies?

  • Only a very limited population will benefit from endovascular therapy
    • Patients with “Severe Strokes”
    • Proximal Large Vessel Occlusions (Anterior Circulation)
    • Salvageable Brain Tissue (Small Infarcted Core and Collateral Blood Flow)

For More on These Topics Checkout:

Systemic tPA in the Treatment of Ischemic Stroke

Endovascular Treatment of Ischemic Stroke

Disclaimer:  This is by no means every piece of literature on the treatment of ischemic stroke, but instead a start to an archive that can continuously be updated.  I was hoping the FOAM community might be willing to help out, to make this an even more robust evidence based archive that we can reference for future needs.  Feel free to leave comments below, all help is welcome, and if there is literature not included feel free to put links in the comments as well.  Appreciate everyone’s help and viva la FOAM!!!!

References:

  1. Multicentre Acute Stroke Trial – Italy (MAST-I) Group. Randomized Controlled Trial of Streptokinase, Aspirin, and Combination of Both in Treatment of Acute ISchaemic Stroke. Multicentre Acute Stroke Trial-Italy (MAST-I) Group. Lancet 1995; 346(8989): 1509 – 14. PMID: 7491044
  2. Hacke W et al. Intravenous Thrombolysis with Recombinant Tissue Plasminogen Activator for Acute Hemispheric Stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995; 274(13): 1017 – 25. PMID: 7563451
  3. The National Institute of Neurological Disorders and stroke rt-PA Stroke Study Group. Tissue Plasminogen Activator for Acute Ischemic Stroke. NEJM 1995; 333(24): 1581 – 7. PMID: 7477192
  4. Multicentre Acute Stroke Trial – Europe (MAST-E) Group. Thrombolytic Therapy with Streptokinase in Acute Ischemic Stroke. NEJM 1996; 335(3): 145 – 50. PMID: 8657211
  5. Donnan GA et al. Streptokinase for Acute Ischmeic Stroke with Relationship to Time of Administration: Australian Streptokinase (ASK) Trial Study Group. JAMA 1996; 276(12): 961 – 6. PMID: 8805730
  6. Hacke W et al. Randomised Double-Biind Placebo-Controlled Trial of Thrombolytic Therapy with Intravenous Alteplase in Acute Ischemic Stroke (ECASSII). Second European-Australasian Acute Stroke Study Investigators. Lancet 1998; 352(9136): 1245 – 51. PMID: 9788453
  7. Clark WM et al. Recombinant Tissue-Type Plasminogen Activator (Alteplase) for Ischemic Stroke 3 to 5 Hours After Symptom Onset. The ATLANTIS STudy: A Randomized Controlled Trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999; 282(21): 2019 – 26. PMID: 10591384
  8. Clark WM et al. The rtPA (Alteplase) 0- to 6-Hour Acute STroke Trial, Part A (A0276g): Results of a Double-Blind, Placebo-Controlled, Multicenter Study. Thromblytic Therapy in Acute Ischemic Stroke Study Investigators. Stroke 2000; 31(4): 811 – 6. PMID: 10753980
  9. Hacke W et al. Thrombolysis with Alteplase 3 to 4.5 Hours After Ischemic stroke. NEJM 2008; 359(13): 1317 – 29. PMID: 18815396
  10. Hacke W et al. Intravenous Desmoteplase in Patients with Acute ISchaemic Stroke Selected by MRI Perfusion-Diffusion Weighted Imaging or Perfusion CT (DIAS-2): A Prospective, Randomized, Double-Blind, Placebo-Controlled Study. Lancet Neurol 2009; 8(2): 141 – 50. PMID: 19097942
  11. IST-3 Collaborative Group. The Benefits and Harms of Intravenous Thrombolysis with Recombinant Tissue Plasminogen Activator Within 6 h of Acute ISchaemic Stroke (The Third International Stroke Trial [IST-3]): A Randomized Controlled Trial. Lancet 2012; 379(9834): 2352 – 63. PMID: 22632908
  12. Albers GW et al. Safety and Efficacy of Desmoteplase Given 3-9 h After Ischemic Stroke in Patients with Occlusion or High-Grade Stenosis in Major Cereral Arteries (DIAS-3): A Double-Blind, Randomized, Placebo-Controlled Phase 3 Trial. Lancet Neurol 2015; 14(6): 575 – 84. PMID: 25937443
  13. Broderick JP et al. Endovascular Therapy After Intravenous t-PA Versus t-PA Alone for Stroke. NEJM 2013; 368(10): 893 – 903. PMID: 23390923
  14. Kidwell CS et al. A Trial of Imaging Selection and Endovascular Treatment for Ischemic Stroke. NEJM 2013; 368(10): 914 – 23. PMID: 23394476
  15. Ciccone A et al. Endovascular Treatment for Acute Ischemic Stroke. NEJM 2013; 368(10): 904 – 13. PMID: 23387822
  16. Fransen PS et al. A Randomized Trial of Intraarterial Treatment for Acute Ischemic Stroke. NEJM 2015; 372(1): 11 – 20. PMID: 25517348
  17. Goyal M et al. Randomized Assessment of rapid Endovascular Treatment of Ischemic Stroke. NEJM 2015; 372(11): 1019 – 30. PMID: 25671798
  18. Campbell BC et al. Endovascular Therapy for ISchemic Stroke with Perfusion-Imaging Selection. NEJM 2015; 372(11): 1009 – 18. PMID: 25671797
  19. Saver JL et al. Stent-Retriever Thrombectomy after Intravenous t-PA vs t-PA Alone in Stroke. NEJM 2015; 372(24): 2285 – 95. PMID: 25882376
  20. Jovin TG et al. Thrombectomy Within 8 Hours After Symptom Onset in Ischemic Stroke. NEJM 2015; 372(24): 2296 – 306. PMID: 25882510
  21. Badhiwala JH et al. Endovascular Thrombectomy for Ischemic Stroke: A Meta-Analysis. JAMA 2015;  314(17): 1832 – 43. [epub ahead of print]
  22. Anderson CS et al. Low-Dose vs Stnadard-Dose Intravenous Alteplase in Acute Ischemic Stroke. NEJM 2016; [epub ahead of print] PMID: 2761018

Post Peer Reviewed By: Anand Swaminathan (Twitter: @EMSwami)

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Salim Rezaie

Clinical Associate Professor of EM and IM at University of Texas Health Science Center at San Antonio (UTHSCSA)
Creator & Founder of R.E.B.E.L. EM
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5 replies
  1. Roberto Cosentini says:

    Great post Salim, as usual.
    Agree 100%:
    1. Great idea to start with a reference list to refer to
    2. Evidence for lysis is weak
    3. Bottom line: one drug doesn’t fit all
    4. We still don’t know the subgroups of patients who are likely to benefit from lysis (the carefully selected pts ACEP GL refer to)
    5. More than 4.000 patients have been enrolled in lysis RCTs. The time for individual patient data metaanalysis has come?

    Thanks again
    Roberto

    Reply
    • Salim Rezaie says:

      Hello Roberto,
      TY for reading and your comments. I agree, it would be nice to see a properly done systematic review/meta-analysis, but I have a feeling that the patient populations, lytic used, and outcomes may be a bit heterogenous. There was just a systematic review and meta-analysis on endovascular therapy for stroke, which I have in the reference list: Badhiwala JH et al. Endovascular Thrombectomy for Ischemic Stroke: A Meta-Analysis. JAMA 2015; 314(17): 1832 – 43. [epub ahead of print]. Hope all is well with you and always appreciate you reading and leaving comments/questions.

      Salim

      Reply
  2. Joe Walter says:

    So SMART EM’s initial overview can be found here: http://podbay.fm/show/512413488/e/1340896151
    And the update here: http://podbay.fm/show/512413488/e/1376320410

    Reply

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