Update on Early Acute Ischemic Stroke Interventions Diana Goodman MD Lead Neurohospitalist Maine Medical Center Assistant Professor of Neurology, Tufts University School of Medicine
I have no disclosures Disclosures
Objectives Discuss the types of ischemic stroke that are amenable to thrombectomy and device options Review past endovascular stroke trials Discuss the two latest endovascular stroke trials Discuss which acute ischemic stroke patients are currently eligible for endovascular therapy
Large Cerebral Vessels: LVO
Time is Brain Neurons lost per minute during large vessel occlusion? 1.8 Million Open up large vessel occlusions Meta-analysis of 33 studies with 1094 patients Good Outcome increase 4.5x with revascularization Rha J-H, Saver JL (2003). Recanalization as a surrogate outcome measure in thrombolytic clinical trials: a meta-analysis. Stroke 34: 347
Clot retrieval /removal devices MERCI (2004) PENUMBRA system (2008) SOLITAIRE AND TREVO (2012)
MERCI Retrieval System
Second Generation: Pneumbra System
Current/Third Generation: Solitaire, Trevo
Works in Theory Where is the evidence?
A bit of history: NEJM March 2013 3 Randomized Endovascular stroke trials Interventional Management of Stroke III (IMS III) trial Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy (MR RESCUE) trial SYNTHESIS Expansion trial All concluded that thrombectomy was NOT superior to medical management in the treatment of acute stroke
The Criticism IMS III and SYNTHESIS included a significant percentage of patients without LVO in the endovascular arm First generation devices in all 3 trials Poor revascularization rates in MR RESCUE
And Then: NEJM Jan 2015 MR CLEAN IA + tpa (233) vs tpa (267) Proximal LVO patients only Treated within 6 hours 81.5% Retrievable Stents in IA group Improved functional independence at 90 days in IA group (32.6% vs 19.1%)
And Then: NEJM March 2015 EXTEND-IA IA + tpa (35) vs tpa (35) All patients with occluded ICA or MCA Treated within 4.5 hours 100% Retrievable Solitaire Stents in IA group Improved functional independence at 90 days in IA group (71% vs 40%) ESCAPE IA + tpa (165) vs tpa (150) All patients with anterior circulation proximal LVO Treated within 12 hours Improved functional independence at 90 days in IA group (53% vs 29%)
And Then: NEJM June 2015 SWIFT PRIME IA + tpa (98) vs tpa (98) All patients with proximal anterior circulation occlusion Treated within 6 hours 100% Retrievable Solitaire Stents in IA group Improved functional independence at 90 days in IA group (60% vs 36%) REVASCAT IA + tpa (103) vs tpa (103) All patients with proximal anterior circulation occlusion Treated within 8 hours 100% Retrievable Solitaire Stents in IA group Improved functional independence at 90 days in IA group (44% vs 28%)
Class 1 AHA/ASA Recommendations: October 2015 Patients eligible for IV r-tpa should receive it even if endovascular treatments are being considered Patients should receive endovascular therapy with a stent retriever if they meet all the following criteria: Prestroke mrs score 0 to 1 Causative occlusion of the ICA or proximal MCA (M1) Age 18 years NIHSS score of 6, ASPECTS of 6, and Treatment can be initiated (groin puncture) within 6 hours of symptom onset Reperfusion to TICI grade 2b/3 should be achieved as early as possible and within 6 hours of stroke onset Use of stent retrievers is preferred to the MERCI device
Uncertain Benefit but Reasonable Beyond 6 hours Causative occlusion of: M2 or M3 portion of the MCAs Anterior cerebral arteries Vertebral arteries Basilar artery Posterior cerebral arteries
Beyond 6 Hours: The Evidence DAWN and DEFUSE 3
DAWN: NEJM Jan 2018 DWI or CTP Assessment with Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention with Trevo Physiologic rather than time based: Clinical-Core Mismatch Significant clinical deficits but still limited infarct size
Pathophysiology of Ischemic Injury: Duration and Degree of CBF 25 Normal neuronal function CBF ml / 100g / min 20 15 10 5 Reversible injury (penumbra) Infarction 0 1 Time (hrs) 2
RAPID Perfusion Software
DAWN Inclusion Group A 80 years of age or older NIHSS had a score of 10 or higher Infarct volume of less than 21 ml Smaller stroke than clinical score would predict -> Presumed Pneumbra Group B Younger than 80 years of age NIHSS had a score of 10 or higher Infarct volume of less than 31 ml Group C Younger than 80 years of age NIHSS had a score of 20 or higher Infarct volume of 31 to less than 51 ml
DAWN Trial 26 center, 19 US, 40 procedures 206, 107 Trevo, 99 Control Funded by Stryker Neurovascular
Safety Outcomes
DAWN Conclusions 100 patients treated with endovascular therapy: 49 Less Disabled 36 Functionally Independent The treatment effect size in DAWN is the highest out of any stroke trials to date Treatment effect persisted 24 hours from TLKW; however, earlier treated patients do better Similar safety profile to thrombectomy performed within 6 hours
DEFUSE 3: NEJM Jan 2018 The Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke Trial Uses Pneumbra on Perfusion vs. Clinical-Core Mismatch Funding National Institutes of Health (NIH) Food and Drug Administration (FDA) investigational device exemption Multicenter (38 US centers), randomized, open-label trial, blinded outcome assessment Terminated early for efficacy at 182 patients 92 endovascular and 90 control. Planned for 476 patients.
RAPID Perfusion Software
DEFUSE 3 Inclusion Criteria 6 to 16 hours after LKW NIHSS 6 Proximal middle cerebral artery or internal carotid artery occlusion (Cervical or IC) Initial infarct size of less than 70 ml Ratio of the volume of ischemic tissue on perfusion imaging to infarct volume of 1.8
DEFUSE 3 Results
DEFUSE 3 Results
DEFUSE 3 vs. DAWN Perfusion imaging based selection of patients with a penumbral (potentially salvageable) region of tissue Enrolled 40% who would not have met DAWN criteria Larger core infarctions, milder stroke symptoms Similar efficacy 16 hours from LKW vs. 24 hours
Class 1 AHA/ASA: January 2018 Patients eligible for IV tpa should receive IV tpa even if EVTs are being considered. (Reworded) In patients under consideration for thrombectomy, observation after IV tpa to assess for clinical response should NOT be performed (Revised) Patients should receive thrombectomy with a stent retriever if they meet the following criteria: (Revised) Prestroke mrs score of 0 to 1 Occlusion of the internal carotid artery or MCA segment 1 (M1) Age 18 years NIHSS score of 6 ASPECTS of 6 Treatment can be initiated (groin puncture) within 6 hours of onset Reperfusion should be achieved as early as possible. (Revised) Goal should be reperfusion to mtici 2b/3 (Reworded) Use of stent retrievers is preferred to MERCI device. (Unchanged)
New Class 1 Recommendation In selected patients with AIS within 6 to 16 hours of LKN who have LVO in the anterior circulation and meet other DAWN or DEFUSE 3 eligibility criteria, mechanical thrombectomy is recommended
Beyond 16 hours In selected patients with AIS within 6 to 24 hours of LKN who have LVO in the anterior circulation and meet other DAWN eligibility criteria, mechanical thrombectomy is reasonable. IIa Recommendation.
Patients to refer to MMC 1. Need CTA: LVO in proximal MCA or ICA Consider ACA, PCA, Basilar, Vertebral arteries 2. Non Con HCT: Small infarct or Normal Completed stroke = No Pneumbra = Ineligible 3. LKW within 24 hours
Questions
References Bhatia R, Hill MD, Shobha N, Menon B, Bal S, Kochar P, Watson T, Goyal M, Demchuk AM. Low rates of acute recanalization with intravenous recombinant tissue plasminogen activator in ischemic stroke: real-world experience and a call for action. Stroke. 2010 Oct;41(10):2254-8. MERCI and Multi MERCI Writing Committee. Effect of time to reperfusion on clinical outcome of anterior circulation strokes treated with thrombectomy: pooled analysis of the MERCI and Multi MERCI trials. Stroke. 2011 Nov;42(11):3144-9. Multi MERCI Investigators, Frei D, Grobelny T, Hellinger F, Huddle D, Kidwell C, Koroshetz W, Marks M, Nesbit G, Silverman IE. Mechanical thrombectomy for acute ischemic stroke: final results of the Multi MERCI trial. Stroke. 2008 Apr;39(4):1205-12. MERCI Trial Investigators. Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial. Stroke. 2005 Jul;36(7):1432-8. SWIFT Trialists. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT): a randomised, parallelgroup, non-inferiority trial. Lancet. 2012 Oct 6;380(9849):1241-9. TREVO 2 Trialists. Trevo versus Merci retrievers for thrombectomy revascularisation of large vessel occlusions in acute ischaemic stroke (TREVO 2): a randomised trial. Lancet. 2012 Oct 6;380(9849):1231-40. Interventional Management of Stroke (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. SYNTHESIS Expansion Investigators. Endovascular Treatment for Acute Ischemic Stroke. N Engl J Med 2013; 368:904-913. 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. Campbell BC, Mitchell PJ, Kleinig TJ, et al. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med 2015;372:1009-18. Saver JL, Goyal M, Bonafe A, et al. Stent-retriever thrombectomy after intra- venous t-pa vs. t-pa alone in stroke. N Engl J Med 2015;372:2285-95. Albers GW, Goyal M, Jahan R, et al. Relationships between imaging assess- ments and outcomes in Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment for acute ische- mic stroke. Stroke 2015;46:2786-94. Goyal M, Menon BK, van Zwam WH, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta- analysis of individual patient data from five randomised trials. Lancet 2016;387: 1723-31. Powers WJ, Derdeyn CP, Biller J, et al. 2015 American Heart Association/Ameri-can Stroke Association focused update of the 2013 Guidelines for the Early Manage- ment of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: a guideline for healthcare professionals from the American Heart Association/ American Stroke Association. Stroke 2015; 46:3020-35. Nogueira RG, Jadhav AP, Haussen DC, et al. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct. N Engl J Med 2018;378:11-21.