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Worldwide Impact of Stroke

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Worldwide Impact of Stroke Tremendous Progress in Age Adjusted Analyses • Epidemiology Outline • Acute treatment » Supportive care » IV fibrinolysis » Endovascular mechanical thrombectomy • Preventive medical therapy » For cardioembolic stroke » For atherothromboembolic Stroke • From ttetrad to pentad » 1 – Diet and lifestyle » 2 - BP lowering » 3 – Antithrombotics » 4 – Statins for cholesterol lowering » 5 – PCSK9 Inhibitors for cholesterol --Age adjusted stroke mortality rates 75%, lowering 1960UCLA - 2010 Stroke Center--Towfighi + Saver, Stroke 2011 R ttkitil tl 50% Stroke Subtypes in Large US Registries Worldwide Impact of Stroke Ischemic Stroke (83%) Hemorrhagic Stroke (17%) Large Artery Atherothrombotic Cardioembolic (30%) Intracerebral • The leading cause of serious disability (30%) Hemorrhage (70%) » Over 16 million strokes / year, including over 10 million nonfatal strokes / year • Second leading cause of dementia • Second leading cause of death » Over 6 million deaths / year » 10% of all deaths worldwide Lacunar (25%) Subarachnoid Hemorrhage (30%) • 85% of the disease burden of stroke (small vessel disease) borne by low-income and middle- Other (10%) income countries Cryptogenic (5%) --Johnston et al, Global variation in stroke burden and UCLA Strokemortality, Center Lancet Neurology 2009 Strategies in Acute Ischemic Stroke Early Supportive Acute Stroke Care Therapy 5-15% Increase in Good Outcomes in Acute Stroke Unit Controlled Trials • Proven • Treat hypoxemia » Continuous pulse oximetry, supplemental oxygen as needed » Recanalization • Maintain normothermia » Early antipyretics/antibiotics » Supportive Care • Avoid hyperglycemia Prevent Clot Propagation » Avoid glucose infusions/use SSI/maintain glucose < 200 mg/dl » • Early parental fluid to support collaterals » Maintenance normotonic IV fluids (IV NS 75-100 cc/h) • Experimental • Permissive hypertension to support collaterals » Neuroprotection » Treat only if >220/120 (lower if tPA) • DVT prophylaxis » Collateral Enhancement » Compression boots/hep/LMWH » Early mobilization • Early swallow assessment to guide oral feeding UCLA Stroke Center UCLA Stroke Center In a typical acute ischemic The Ischemic Penumbra stroke, every minute the brain loses Irreversible Core Infarct • 1.9 million neurons • 14 billion synapses Ischemic Penumbra zone of salvageable • 7.5 miles myelinated fibers tissue surrounding core infarct -- Saver, Stroke 2006 Two Major Strategies in Acute Ischemic Onset to Treatment Time for IV TPA and Odds of Stroke Treatment Excellent Outcome Reperfusion Neuroprotection • Pooled, patient level analysis • 8 trials » NINDS 1 and 2 » ATLANTIS A and B » ECASS 1, 2, and 3 » EPITHET • 3670 patients UCLA Stroke Center UCLA Stroke Center --Lees et al, Lancet 2010 TPA Treatment Time and Benefit Magnitude 58,353 Patients from 1395 GWTG-Stroke Hospitals Improvement Over Time in GWTG-Stroke in --Saver et al, JAMA 2013 the Use of IV rt-PA in Eligible Patients Among 1000 patients, for every 15 Baseline YR1 YR2 YR3 YR4 YR5 min acceleration of tPA treatment 100% • 18 more will have improved ambulation at discharge 80% 72.65% 72.84% 69.10% – Including 8 more who will 65.00% ambulate fully independently • 13 more will be discharged to a 60% 53.46% more independent environment 42.09% – Including 7 more discharged to 40% home • 4 fewer patients will die prior to 20% discharge 0% IV rt PA 2 Hour Substantial Opportunity to Improve Timeliness of IV rt-PA in Ischemic Stroke Door-to-IV rt-PA within 60 minutes 2005 2006 2007 2008 2009 100% 80% 60% 40% 25.80% 27.40% 24.10% 22.30% 24.70% 20% 0% DTN within 60 min Target: Stroke Best Practice Strategies Target: Stroke The Time is Now 1. *EMS Pre-Notification 7. *POC Laboratory Testing Door-to-IV rt-PA within 60 minutes 2. Stroke Toolkit 8. *Premix TPA 100% 3. Rapid Triage and Stroke 9. *Rapid TPA Access - 80% Team Notification store TPA in ED/radiology, start in imaging suite 60% 4. *Single Call Activation 50.0% System 10.Team approach 40% 27.4% 5. *Transfer Directly to CT 11.*Prompt data feedback 20% 6. Rapid Brain Imaging 0% •2009 •Goal DTN within 60 min IV TPA Under 3 Hours – Patient Education Target: Stroke Impact and Success in US: Fonarow et al, JAMA 2014 • Joint AHA-AAN-ACEP 0.6 text tool to educate 0.5 patients and families • UCLA icon array tool 0.4 based on AHA-AAN- 0.3 ACEP 0.2 % DTN Time ≤60 Minutes ≤60 Time DTN % Target: Stroke Initiation 0.1 --Gadhia et al, Stroke 2010 (P<0.0001 for comparison of the two slopes) 0 UCLA Stroke Center 3Q2 3Q3 3Q4 4Q1 4Q2 4Q3 4Q4 5Q1 5Q2 5Q3 5Q4 6Q1 6Q2 6Q3 6Q4 7Q1 7Q2 7Q3 7Q4 8Q1 8Q2 8Q3 8Q4 9Q1 9Q2 9Q3 9Q4 0Q1 0Q2 0Q3 0Q4 1Q1 1Q2 1Q3 1Q4 2Q1 2Q2 2Q3 2Q4 3Q1 3Q2 3Q3 Target: Stroke Phase 2 Time Trend in the Proportion of Patients with DTN Times within 45 Minutes Pre-Target: Stroke and During Target: Stroke Phase I and II • Target: Stroke Elite » DTN ≤ 60m in 75% Time Period Estimate P‐ » DTN ≤ 45m in 50% (per year) (95% CI) value <.0001 Pre‐Target: 0.12 (‐0.20, 0.4741 Stroke 0.43) Target: Stroke 2.87 (2.49, <.0001 Phase I 3.25) Target: Stroke 10.20 (5.92, 0.0018 Phase II 14.48) UCLA Stroke Center Door to Needle Times with “Direct to CT” or “ED Pitstop” in Best Practice Hospitals Stroke Center Median Door to Needle Times Helsinki, Finland 20 mins Mobile Stroke Units for Prehospital Thrombolysis Erlangen, Germany 25 mins Wash U, St. Louis 39 mins --Meretojoa et al, Neurology 2012 --Korhmann et al, Int J Stroke 2011 --Ford et al, Stroke 2012 UCLA Stroke Center TPA Frequency and Speed CT p CT p Control Ambulan value Ambulan value Weeks ce ce Weeks Patients N 1804 3213 2969 Pct of AIS 32.6% <0.00 28.9% <0.00 21.1% --JAMA, April 2014 1 1 DTN Hosp (min) 42 Alarm to Hosp 85 <0.00 67 <0.00 35 (min) 1 1 Alarm to 38 <0.00 44 <0.00 52 Imaging 1 1 *Primary Endpoint UCLA Stroke Center ImaUCLAgin Strokeg to CenterTPA 14 <0.00 17 <0.00 24 No difference in efficac or safet o tcomes MSU CT Dispatcher impression: Stroke Provider impression: Stroke NIHSS : 7 LAMS: 3 Clinical scenario: 76 year old woman with history of prior TIA (lip numbness & dysarthria 5 month prior), presenting with witnessed acute onset left face/arm weakness, difficulty with ambulation Acute NIHSS 7: left face/arm weakness, numbness, ataxia, dysarthria, sensory LKWT-to-Tx time: 45 min MSU admission-to-CT time: 5 min MSU admission-to-needle time: 19 min 24 hr NIHSS 1: mild sensory deficit in left arm Hospital MRI BEnefits of Stroke Treatment Delivered Using a Mobile Stroke Unit (BEST-MSU) Trial • Cluster-control RCT » 5 EMS Regions USA » 1 week on, 1 week off » Patients • ~9000 assessed • ~2000 enrolled » ~1000 fully tPA eligible • Key entry criteria » LKW within 4.5h prior to ambulance evaluation » tPA eligible prior to CT/labs • Outcome: Utility-weighted mRS at 90d • Timeline: 2014-2021 Growing Worldwide Use of Catheter-Based Reperfusion Therapies Mobile Stroke Units UCLA Stroke Center --Fassbender, Grotta,Walter, Grunwald, Ragoschke-Schumm, Saver, Lancet Neurol 2017 Acute Mechanical Recanalization Strategy Historical Development of Endovascular Depends on Target Occlusion Composition Technologies for Acute Recanalization Embolus In Situ Atherothrombosis Technology First Human Studies • Relatively normal • Substantial local IA microcatheter lysis 1988 (1999) recipient artery atherosclerotic plaque IA angioplasty 1994 • Strategy: remove the • Strategy: Crack the IA aspiration thrombectomy 2001 (2009) thrombus plaque IA ultrasound sonothrombolysis 2003 IA implanted stents 2003 •Retrievers • Angioplasty IA laser clot destruction 2004 • Aspirators • Stents IA Archimedes screw 2004 •+/- Lytics •+/- Lytics IA coil retrievers 2004 (2004) IA basket/brush retrievers 2006 IAUCLA stent Stroke retrievers Center 2010 (2010) UCLA Stroke Center Mechanical Thrombectomy Devices Mechanical Thrombectomy Devices Covered Covered Coil Basket Brush Aspiration Stent Coil Basket Brush Aspiration Stent Stent Stent Retriever Retriever Retriever Catheter Retriever Retriever Retriever Retriever Catheter Retriever Retriever Retriever UCLA Stroke Center UCLA Stroke Center UCLA – MCA Occlusion 30-Year-Old Female – Baseline NIHSS 24 Symptom Onset to Final Angiogram – 5:37 NIHSS 24 hours 1 mRS 5 days post 0 30 days post 0 90 day post 0 UCLA Stroke Center de ce o e e Independence (mRS≤2) at 3 Months Trial ERT+Med MedRx OR P value Rx MR CLEAN 32.6% 19.1% 2.05 0.0007 ESCAPE 53.0% 29.3% 2.73 0.00003 EXTEND-IA 71.4% 40.0% 3.75 0.009 SWIFT PRIME 60.2% 35.5% 2.75 0.0008 REVASCAT 43.7% 28.2% 1.98 0.021 All (weighted 46.1% 26.4% 2.39 <0.0000000 avg) 1 Odds that SR ERT is beneficial are more than 100,000,000 UCLA Stroke Center to 1 NNTs for Cerebral and Cardiac Ischemia Binary Outcomes Thrombectomy for AIS (vs Lysis) (4) Independence Endovascular therapy if patients meet all the following criteria IV Lytics • Prestroke mRS score 0-1 for AIS (vs ASA) (10) • Received IV tPA (Ia) or tPA-ineligible (IIa) Nondisability • ICA or M1 MCA occlusion • Age ≥ 18 yo • NIHSS ≥ 6 PCI • ASPECTS ≥ 6 for STEMI (vs Lysis) (29) • Treatment start (puncture) within 6h of onset Mortality UCLA Stroke Center UCLA Stroke Center Time to Puncture Time to Puncture and Thrombectomy Outcome and Thrombectomy Outcome HERMES HERMES Collaboration Collaboration 2.3 2.5 2.9 •NNTs 3.4 4.2 5.5 8.6 7.3 hrs 7.3 hrs --Saver et al, JAMA 2016 --Saver et al, JAMA 2016 Minutes Matter • IV TPA Progressors: Fast / Slow / Variable » Every 8 minute delay causes 1 fewer of 100 treated patients to benefit in improved ambulation • IA Neurothrombectomy » Every 4 minute delay causes 1 fewer of 100 reperfused patients to benefit in reduced final disability
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