Stroke Therapy: Faster is Be*er

Transcription

1 1/1/16 Stroke Therapy: Faster is Be*er Alteplase (rt-pa) data (mostly) Stroke 795, each year. 55, first/new strokes 5th Leading Cause of Death in US 129, (CDC 213) We live in the Stroke Belt (highest stroke mortality) Nojan Valadi, MD January 216 DefiniVons Stroke: $3 billion annual cost Leading cause of disability What we can do depends on: The Type of Stroke The Vme from onset of symptoms Focal neurological dysfuncvon due to cerebrovascular infarcvon or hemorrhage in cerebral, revnal or spinal Vssue TIA: Brief episode of neurological dysfuncvon from focal temporary cerebral, revnal, or spinal ischemia without evidence of infarcvon Types of Stroke Ischemic Stroke: The Penumbra 1

2 1/1/16 Time is Brain SystemaVc literature-review of studies using quanvtavve neurostereology and stroke neuroimaging to calculate brain loss per unit of Vme in stroke Typical final volume of large vessel, supratentorial ischemic stroke = 5 ml Mean duravon of non-lacunar stroke evoluvon is 1 hours (R:6 to 18 hrs) Average number of neurons in the human forebrain is 22 billion Per Hour 12 mil neurons, 83 billion synapses, and 7 miles of myelinated fibers are lost Per Minute 1.9 mil neurons, 1 billion synapses, and 7.5 miles of myelinated fibers are lost The brain ages 3.6 years each hour without treatment Saver JL. Time is brain quanvfied. Stroke. 26;37: Stroke Chain of Survival LKWT FSBS, BP AnVcoagulant? DetecVon signs and symptoms Dispatch Call 911 and priority EMS dispatch Delivery Prompt transport and novficavon Door Immediate ED triage Data ED eval, labs, and CT imaging Decision Dx and decision about therapy Drug AdministraVon of appropriate Rx/Tx RecanalizaVon: Thrombolysis Intravenous: tpa Not: urokinase, streptokinase, desmoteplase Intra-arterial Mechanical: Solitaire Flow RestoraVon Device Trevo Retriever Penumbra AspiraVon Device Merci tpa, urokinase (pro-uk) Concerns about fast Rx Rushed assessments Dosing errors Greater likelihood of complicavons Background Less than 3% of eligible stroke pavents were being treated within the guideline-recommended door-toneedle Vme for tpa administravon and this measure had not improved over Albers et al, JAMA. 2;283(9): Fonarow et al, Circula5on. 211;123(7): NINDS ECASS 1,2,3 ATLANTIS A, B EPITETH IST-3 NINDS A, B Stroke Trials 2

3 1/1/16 RelaVonship between Time and Outcome 9 day Outcomes: NINDS Trial part 2 ECAS III Trial IV tpa 3 hour window NNT for 1 addivonal pavent to have a bejer outcome by 1 or more grades on the mrs as a result of tpa treatment is 3.1 NNH for any ICH 17.2 NNH for 1 more pavent to have a worsened outcome by any degree (1 mrs grade) ajributable to tpa-related SICH is between 29.7 and.1. tpa risk and benefits ECASS III IV tpa 3-.5 hour window NNT for 1 addivonal pavent to have a bejer outcome by 1 or more grades on the mrs as a result of tpa treatment is 6 NNH for any ICH 16 NNH for 1 more pavent to have a worsened outcome by any degree (1 mrs grade) ajributable to tpa-related SICH is min, n=311; min, n=618; min, n=81; min, n=16. Values do not equal 1% because of rounding. Time is an effect modifier The ATLANTIS, ECASS, and NINDS rt-pa Study Group InvesVgators. Lancet 2; 363 (911):

4 1/1/16 FuncVonal Outcomes Pooled Analysis of Stroke Trials NINDS ATLANTIS A ATLANTIS B ECASS II ECASS III EPITETH Hacke W, Donnan G, Fieschi C, Kaste M, von Kummer R, Broderick JP, et al. AssociaVon of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-pa stroke trials. Lancet. 2;363: Lees KR, Bluhmki E, von Kummer R, Broj TG, Toni D, Groja JC, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 21;375: Odds ratio and 95% CI Odds ratio and 95% CI A Modified Rankin score 1 B Composite endpoint 5 Odds ratio estimated by model 5 95% CI for estimated odds ratio C Mortality D Parenchymal haemorrhage type OTT (min) OTT (min) Benefit of Alteplase (rt-pa) NNT: 3 treated with alteplase within 3 hrs NNT: 6 treated within.5 hrs of symptom NNT for Excellent Outcome (mrs -1): 9 mins - NNT: mins NNT: mins NNT: 15 Lees KR, Bluhmki E, von Kummer R, Broj TG, Toni D, Groja JC, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 21;375: Lees KR, Bluhmki E, von Kummer R, Broj TG, Toni D, Groja JC, et al. Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Lancet. 21;375: Emberson et al, Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual pavent data from randomised trials, Lancet. 21: 38 (9958); Meta-analysis of NINDS, ATLANTIS A, B, ECASS 2,3, EPITETH, IST-3 Emberson et al, Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual pavent data from randomised trials, Lancet. 21: 38 (9958);

5 1/1/16 Human Nature? Onset-to-door (min) time onseter= Doorndle Strbian et al. RelaVonship between onset-to-door Vme and door-to-thrombolysis Vme: a pooled analysis of 1 dedicated stroke centers.stroke. 213; : Door-to-needle time (min) 2 For each 1 minute delay in ER arrival, treatment was 18 minutes faster! Parkinson s Law (see The Economist, November 19, 1955) AHA/ASA Time Goals and GWTG Cyril Northcote Parkinson -BriVsh Civil Service Official Work expands so as to fill the Vme available for its complevon. Frst sentence of a humorous essay published in The Economist in 1955 Reprinted with other essays in the book Parkinson's Law: The Pursuit of Progress (London, John Murray, 1958). Corollaries: If you wait unvl the last minute, it only takes a minute to do. Work contracts to fit in the Vme we give it. GWTG- Stroke Program - Fonarow et al. In-Hospital Outcomes 129,31 ischemic strokes ~6.5 yrs at 182 hospitals 25,5 (19.7%) treated w/in tpa 3 hrs fom onset Mean DTN 79.3mins, Median DTN 78mins 679 (26.6%) pavents with DTN Vmes 6 minutes and 18,71 (73.%) with DTN Vmes >6 minutes Effect on In-hospital mortality: every 15min ê reducvon in DTN è 5% lower odds of inhospital mortality (AdjOR.95, 95% CI , P=.7) Fonarow GC, Timeliness of Vssue-type plasminogen acvvator therapy in acute ischemic stroke: pavent characterisvcs, hospital factors, and outcomes associated with door-to-needle Vmes within 6 minutes. Circula5on. 211;123(7): ImplementaVon of Best PracVces and decreasing DTN Vmes GWTG Registry ImplementaVon of best pracvces decreased DTN Vme from 77 mins to 67 mins % geung alteplase in 6 mins increased from 26.5% to 1.3% % geung alteplase in 6 mins increased from29.6% in the 3 mos prior to intervenvon (fourth quarter of 29) to 53.3% in the final post-intervenvon quarter (third quarter of 213) (P <.1) In-hospital all-cause mortality improved from 9.93% to 8.25% (adjusted OR=.89 [95% CI,.83-.9], P <.1) sich within 36 hours was less likely to occur (5.68% vs.68%; adjusted OR,.83 [95% CI, ], P <.1) Discharge to home was more frequent (37.6% vs 2.7%; adjusted OR, 1.1 [95% CI, ], P <.1) ImplementaVon of Best PracVces led to improvement in DTN Vmes and lower inhospital mortality and intracranial hemorrhage, along with an increase in the percentage of pavents discharged home. Fonarow et al. DTN Times for TPA Administra5on and Clinical Outcomes in Acute Ischemic Stroke Before and AFer a Quality Improvement Ini5a5ve. JAMA. 21;311(16):

6 1/1/16 Time to Treatment With Intravenous Tissue Plasminogen AcVvator and Outcome From Acute Ischemic Stroke GWTG Registry: 58,353 tpa-treated pavents Mean OTT Vme was 1 minutes 9.3% (5,) had OTT Vme -9 min, 77.2% (5,29) had OTT Vme min, and 13.6% (7,92) had OTT Vme min. Median pretreatment NIHSS in 87.7% of pavents was 11 PaVent factors most strongly associated with shorter OTT Greater stroke severity (OR 2.8; 95% CI, per 5-point increase) Arrival by ambulance (OR 5.9; 95% CI,.5-7.3) Arrival during regular hours (OR.6; 95% CI, ) Time to Treatment With Intravenous Tissue Plasminogen AcVvator and Outcome From Acute Ischemic Stroke In Hospital Mortality was 8.8% sich was.9% 19,91 (33.%) pavents achieved independent ambulavon at hospital discharge 22,51 (38.6%) pavents were discharged to home Ever 15-minute increment of faster treatment was associated with Reduced in-hospital mortality (OR,.96; 95% CI, ; P<.1) Reduced sich (OR,.96; 95% CI, ; P<.1) Increased achievement of independent ambulavon at discharge (OR, 1.; 95% CI, ; P<.1) Increased discharge to home (OR, 1.3; 95% CI, ; P<.1) Saver et al, JAMA. 213;39(23): Saver et al, JAMA. 213;39(23): What about Endovascular Treatment? IniVally failed to show impact on outcomes But a review of impact of recanalizavon Vme on outcome showed a different story 5 pts in IMS I + II with reperfusion Good Outcome: 9 day mrs -2 Khatri P, Abruzzo T, Yeajs SD, Nichols C, Broderick JP, Tomsick TA. Good clinical outcome a{er ischemic stroke with successful revascularizavon is Vme-dependent. Neurology. 29;73: IMS-III Data analysis Data supports Faster Treatment Khatri P. et al., Time to angiographic reperfusion and clinical outcome a{er acute ischaemic stroke: an analysis of data from the IntervenVonal Management of Stroke (IMS III) phase 3 trial. Lancet Neurol. 21 Jun;13(6):567-7 Faster DetecVon and Dispatch Faster PresentaVon to the Emergency Room Faster Emergency Room Triage Faster Stroke EvaluaVon Faster IV thrombolysis Faster evaluavon for Endovascular therapy Faster Groin Puncture / RecanalizaVon = Be*er Outcomes 6

7 1/1/16 Faster is Bejer: How can we speed things up? Telestroke ImplementaVon of EMS Transport / Air Transport Services Coverdell-Murphy Act / Transport to Appropriate Stroke Centers OpVmizaVon of ER Processes Telemedicine / Telestroke Mobile Stroke Units Telestroke REACH MCG UPMC STRokE DOC CO-DOC STARR Network MUSC Reach Telemedicine by ios RUN-FC France TRUST-TPA France TELESTROKE Finland Telestroke GSTT UK/ London Telemedicine by iphone Mobile Stroke Unit University Texas Health System EsVmated Cost: $5, 7

8 1/1/16 Give the Juice! And give it fast!!! 8