Drano vs. MR CLEAN Review of New Endovascular Therapy for Acute Ischemic Stroke Patients Peter Panagos, MD, FACEP, FAHA Associate Professor Emergency Medicine and Neurology Washington University School of Medicine
Disclosures Speaker s Bureau: Genentech Research Funding: NIH, St Luke s Hospital (KC) Consultant: AHA/ASA ACLS 2016 (Volunteer) Scientific Advisory Board: Pulse Therapeutics
Burden of Cerebrovascular Disease Stroke Death Rates 2008-2010. Adults > 34 years of age, by county Data Source: National Vital Statistics System and US Census Bureau
The Penumbra Shrinks as Time from Onset of Ischemia Increases Oligemia: > 20 ml/100g/min Penumbra: 8 20 ml/100g/min Core: < 6-8 ml/100g/min
Time is Brain Time interval NNT for one Absolute risk good outcome reduction 0-90 min 5 20% Combined data from ECASS I-III, EPITHET, NINDS, ATLANTIS; Lees et al, Lancet 375:1695-703, 2010. 91-180 min 9 11% 181-270 min 15 6.7%
Faster Stroke Treatment is Better Treatment Patients treated within 60 mins. experience improved outcomes, including lower in-hospital mortality and reduced long-term disability GC Fonarow et al. JAMA. 2014;311(16):1632-1640 Saver et al. JAMA. 2013;309(23):2480-8
Basic Stroke Anatomy 101 Goyal M et al. N Engl J Med 2015;372:1019-1030
IV tpa Doesn t Always Work Angiographic evaluation to identify presence and location of clot and effect of agent in 93 patients IV t-pa (0.12-0.75 mg/kg) given 0-6 hours Angiographic Findings 26% (12/46) complete or partial lysis in M1, M2 9% (2 of 23) lysis in ICA Similar data by del Zoppo (Ann Neurol 1992) and Tomsick (AJNR 1996), Bhatia (Stroke 2010) Wolpert S, et al AJNR 1993; 14: 3-13.
Longer Clot Length = Less Chance to Work Reidel et al. Stroke 2011
Recent results of four trials
Now the Science.
MR-CLEAN Aim: To assess the effect of intra-arterial (IA) treatment on functional outcome after acute ischemic stroke (AIS) caused by a proven intracranial arterial occlusion, against a background of best medical management (with or without IV tpa) Design: multicenter, prospective randomized open, blinded endpoint (PROBE)
MR-CLEAN Study population: Netherlands Inclusion criteria: AIS, CTA w/ anterior circulation occlusion, age 18, NIHSS 2 Intervention: open Mechanical treatment, delivery of thrombolytic agent, or both Timeframe: IA treatment within 6 hours
MR-CLEAN Primary outcome: modified Rankin score (mrs) at 90 days Several clinical secondary outcomes (not covered here) Several neuro-imaging outcomes (not covered here)
MR-CLEAN
MR-CLEAN SWIFT-PRIME EXTEND-IA ESCAPE N Baseline NIHSS % with IV tpa Device Usage mrs 2 @ 90d 500 patients - 233 IAT - 267 control - 17 IAT - 18 control - 87% IAT - 91% control 97% stent retriever IAT: 32.6% Control: 19.1% NNT for mrs 0-2 at 90 days sich 7 IAT: 7.7% Control: 6.4%
SWIFT-PRIME Aim: To determine if subjects experiencing an AIS due to large vessel occlusion (LVO), treated with combined IV tpa and Solitaire device within 6 hours of symptom onset, have less stroke-related disability (mrs) than subjects treated with IV tpa alone. Design: multicenter, prospective randomized open, blinded endpoint (PROBE)
SWIFT-PRIME Study population: United States and Europe Inclusion criteria: AIS, CTA/MRA w/ occlusion at intracranial ICA / M1 / carotid terminus, age 18-80, NIHSS 8-29, pre-stroke mrs 1 Intervention: Solitaire device (stent retriever) Timeframe: IV treatment within 4.5 hours and IA treatment within 6 hours (within 90 minutes of qualifying imaging)
SWIFT-PRIME Primary outcome: modified Rankin score (mrs) at 90 days Several clinical secondary outcomes (not covered here) Several neuro-imaging outcomes (not covered here)
SWIFT-PRIME Enrollment ended early due to MR-CLEAN (n=196)
MR-CLEAN SWIFT-PRIME EXTEND-IA ESCAPE N Baseline NIHSS % with IV tpa Device Usage mrs 2 @ 90d 500 patients - 233 IAT - 267 control - 17 IAT - 18 control - 87% IAT - 91% control 97% stent retriever IAT: 32.6% Control: 19.1% 196-98 IAT - 98 control - 17 IAT - 17 control - 100% IAT - 100% control Solitaire IAT: 60.2% Control: 35.5% NNT for mrs 0-2 at 90 days 7 4 sich IAT: 7.7% Control: 6.4% IAT: 1.0% Control: 3.1%
EXTEND-IA Rationale: To select patients with the best chance of benefit from reperfusion ( Dual Target ) with a proven major vessel occlusion and salvageable tissue with ischemic core < 70 ml (CT perfusion), treat as fast as possible, using the most effective device (stent retriever) Design: multicenter, prospective randomized open, blinded endpoint (PROBE)
EXTEND-IA Study population: Australia & New Zealand Inclusion criteria: AIS, CTA/MRA w/ occlusion at ICA / M1 / M2 PLUS mismatch with ischemic core < 70mL, age 18, no specified NIHSS, pre-stroke mrs 1 Intervention: Solitaire device (stent retriever) Timeframe: IV treatment within 4.5 hours and IA treatment within 6 hours
EXTEND-IA Primary outcomes: 24 hour MRI reperfusion 3 day NIHSS Several clinical secondary outcomes mrs at 90 days Several neuro-imaging outcomes (not covered here)
EXTEND-IA Enrollment ended early due to MR-CLEAN (n=70)
MR-CLEAN SWIFT-PRIME EXTEND-IA ESCAPE N 500 patients - 233 IAT - 267 control 196-98 IAT - 98 control 70-35 IAT - 35 control Baseline NIHSS - 17 IAT - 18 control - 17 IAT - 17 control - 17 IAT - 13 control % with IV tpa - 87% IAT - 91% control - 100% IAT - 100% control - 100% IAT - 100% control Device Usage 97% stent retriever Solitaire Solitaire mrs 2 @ 90d IAT: 32.6% Control: 19.1% IAT: 61.1% Control: 35.5% IAT: 71% Control: 40% NNT for mrs 0-2 at 90 days 7 4 3 sich IAT: 7.7% Control: 6.4% IAT: 1.0% Control: 3.1% IAT: 0% Control: 6%
ESCAPE Aim: to answer the question: Do I take this patient to endovascular treatment (thrombectomy)? Design: multicenter, prospective randomized open, blinded endpoint (PROBE)
ESCAPE Study population: Canada, US, Korea, UK & Ireland Inclusion criteria: AIS, CTA w/ occlusion at carotid terminus / M1 / 2 or more M2s PLUS moderate to good collaterals, age 18, NIHSS > 5, good functional status prior to stroke Intervention: mechanical thrombolysis (including stent retriever) Timeframe: Last-seen-well time to randomization < 12 hours and IA treatment started within 60 minutes of qualifying imaging
Multi-phase CTA Conventional Mid Venous Late Venous Arch to Vertex Phase Phase
ESCAPE Primary outcome: modified Rankin score (mrs) at 90 days Several clinical secondary outcomes (not covered here) Several neuro-imaging outcomes (not covered here)
ESCAPE Enrollment ended early due to MR-CLEAN (n=315)
MR-CLEAN SWIFT-PRIME EXTEND-IA ESCAPE N 500 patients - 233 IAT - 267 control 196-98 IAT - 98 control 70-35 IAT - 35 control 315-165 IAT - 150 control Baseline NIHSS - 17 IAT - 18 control - 17 IAT - 17 control - 17 IAT - 13 control - 16 IAT - 17 control % with IV tpa - 87% IAT - 91% control - 100% IAT - 100% control - 100% IAT - 100% control - 73% IAT - 79% control Device Usage 97% stent retriever Solitaire Solitaire 86% stent retriever mrs 2 @ 90d IAT: 32.6% Control: 19.1% IAT: 61.1% Control: 35.5% IAT: 71% Control: 40% IAT: 53% Control: 29.3% NNT for mrs 0-2 at 90 days 7 4 3 4 sich IAT: 7.7% Control: 6.4% IAT: 1.0% Control: 3.1% IAT: 0% Control: 6% IAT: 3.6% Control: 2.7%
SUMMARY
MR-CLEAN SWIFT-PRIME EXTEND-IA ESCAPE Baseline NIHSS - 17 IAT - 18 control - 17 IAT - 17 control - 17 IAT - 13 control - 16 IAT - 17 control % with IV tpa Revasc Rates (TICI 2b/3 ) - 87% IAT - 91% control - 100% IAT - 100% control - 100% IAT - 100% control - 73% IAT - 79% control IAT: 58.7% IAT: 88% IAT: 86% IAT: 72.4% mrs 2 @ 90d IAT: 32.6% Control: 19.1% IAT: 61.1% Control: 35.5% IAT: 71% Control: 40% IAT: 53% Control: 29.3% NNT mrs 0-2 at 90d 7 4 3 4 sich IAT: 7.7% Control: 6.4% IAT: 1.0% Control: 3.1% IAT: 0% Control: 6% IAT: 3.6% Control: 2.7% Mortality at 90 days IAT: 21% Control: 22% IAT: 12.2% Control: 25.8% IAT: 9% Control: 20% IAT: 10% Control: 19%
Summary Slightly different inclusion/exclusion criteria Now Level I A Recommendations AHA Focused Update Statement (March 2015) All focused on minimizing time to intervention Fairly consistent results overall NNT = 3-4 for mrs 0-2 at 90 days NNT = 8 for MRS 0-2 at 90 days for IV tpa How do we implement this new evidence going forward?
What Does This Mean For Prehospital Care?
2015: All Stroke Care is Note Equal Specialty Care is Limited 91 CSC 1,200 PSC TBD ASRH Stroke Care is Comprehensive Large AIS, ICH, SAH Multi-system disease Surgical or endovascular expertise 24/7, 365 NICU Research, Education Outcomes
Why Doesn t EMS Just Triage the Right Patient to the Right (CSC) Hospital?
EMS Field Triage in Stroke: Not Exact Science Yet Often inaccurate for stroke type, size, severity Cannot predict deterioration or complications Patient preference Politics (e.g. Regional plans, CMS rules, etc ) Messaging unclear (e.g. Marketing vs. Quality)
Next Steps in Stroke Care Regionalization Coordination Selective Triage Track & Report Quality Adapt to Changes in Evidence
St Louis EMS Regional Plan Draft-Approved
AHA/ASA Mission: Lifeline Stroke Routing Template Draft
Thank You!