Neuroradiology in hyperacute stroke: what is the UK position? Dr Shelley Renowden Bristol
NICE HIS July, 2013 The current evidence on mechanical clot retrieval for treating acute ischaemic stroke shows that efficacy is unproven.suitability for thrombolysis can be guided by criteria used in the PISTE trial. 1.1 Patients with acute ischaemic stroke for whom thrombolysis is unsuitable/failed;.only performed with special arrangements for clinical governance, consent, audit, research 1.2 Patients with acute ischaemic stroke for whom thrombolysis is suitable:..used only in the context of research, which should in be RCTs comparing mechanical clot retrieval or the current methods of management and should report details of patient selection, timing of the intervention after onset of symptoms, the devices and techniques used, complications and functional outcomes NICE encourages clinicians to enter patients into RTs such as PISTE we have been doing thrombectomy in selected patients.
ischaemic stroke patient age co-morbidites (age, diabetes) NIHSS site, extent of occlusion collateral circulation extent of recanalisation time from ictus to recanalisation SICH leukoariosis
NIHSS NIHSS >20-4-16% chance of good outcome at 1yr cf 60-70% in those with NIHSS <10 see Balami et al, Brain, 2013, 136, 3528-3553)
IV TPA / NIHSS: STOPSTROKE good poor outcome NIHSS 0-5 n=352 no iv tpa 81% 19% iv tpa 70% 30% p=0.31 NIHSS 6-10 n= 109 no iv tpa 52% 48% iv tpa 74% 26% p=0.038 NIHSS 11-15 n=79 no IV tpa 35% 65% iv tpa 50% 50% p=0.15 NIHSS >=16 n= 109 no iv tpa 12% 88% iv tpa 27.5% 72.5% p=0.034 Gonzalez et al, Stroke, 2013, 44, 3109-3113
NIHSS and LVO? median NIHSS in M1 occlusion is 14 NIHSS 10+ 81% PPV LVO 48% sensitivity 55% of pts with NIHSS 10 - had LVO LVO in 90% NIHSS 16+ LVO in 100% NIHSS 27+ Maas et al, Stroke, 2009, 40, 2988-2993
Effect of IV TPA and occlusion site prox MCA distal MCA ICA/MCA TICA BA n 165 116 22 17 10 NIHSS 18 (6-32) 13 (3-29) 19(6-29) 20(11-28) 27 TIMI 3 30% 44% 27% 6% 35% <2hr p=0.007 early 16% 33% 24% 0% 25% Improvement p=0.004 90 day 25% 52% 21% 18% 25% mrs<=1 p<0.001 mortal 24% 17% 14% 45% 75% 90 day p=0.0024 Saqqur et al Stroke 2009 (Clotbust)
location of thrombus, outcome, anterior circulation stroke IVT, within 3 hours impact of thrombus location on CTP, % salvaged brain ICA M1p M1d M2-3 age` 70 68 70.5 69.5 NIHSS 18 14 12 9 onset to TPA 138 133 117 133 ASPECTS 8 8 9.5 9 infarct vol 150 64 27 19ml (mean) mrs 0-2 0 22% 82% 86% 90 days Sillanpaa et al, AJNR, 2013
final infarct volumes: EVT cf IVT in LVO 203 pts; LVO; mean age 66; median NIHSS 19; 2009-2011 median infarct volume smaller for EVT (42cm3) cf IVT (109cm3) no Rx group (110cm3) EVT IV TICA occ 75 190 M1 MCA 39 109 M2 33 59 NIHSS 14+ 46 149 8-13 22 44 Rangaraju et al, JAMA Neurology, 2013, 70, 831-836
clot length occlusion location is the strongest predictor of clot length (Kamaliam et al, Stroke 2013, 44, 3553-3556) clot length 8+mm in 94% TICA, 73% M1 and 22% M2 occlusions IVT has no potential to recanalise occluded vessels if thrombus length > 8mm (Riedel et al, Stroke 2011, 42, 1775-1777)
7+ - predicts independent outcome
57F, AF, 3.5 hours after ictus left facial weakness, dense right hemiparesis (0/5) extensor R plantar left VFD severe expressive dysphasia NIHSS 20 ASPECTS 7
CTA normal parenchyma 71 F, NIHSS 19 80 sec CT Brain
Recanalise Recanalisation using combined intravenous altepase and neurointerventional algorithm for acute ischaemic stroke n 90/7 favourable early neuro improvement outcome TIMI 0-1 7 0% 14% TIMI 2 9 22% 44% TIMI 3 37 76% 73% p <0.0001 0.006 Mazighi et al, Stroke, 2009
IV TPA- recanalisation rates CTA database 2002-2009 - Calgary Stroke programme 216 pts- IV TPA; 103 went on to IA TPA M1-32.3%(43.1%); TICA 4% (39.1%); M2 31%(61.5%); BA 4% (52%) 60.5% who recanalised had good outcomes cf 24.3% who did notstrongest predictor of good outcome early recanalisation is associated with a better outcome than late Bhatia et al, Stroke, 2010, 41, 2254-2258
time from ictus to recanalisation IMS III - every 30 min delay in reperfusion is associated with 10% relative reduction in probability of a good outcome MRCLEAN OR for good outcome decreasing from 3.0 at 3.5 hours post ictus to reperfusion to 1.5 at 6 hours for each hour delay from ictus to TICI 2b/3 odds of good clinical outcome decreased by 38% - Menon et al, Stroke 2014 for every minute of arterial occlusion 1.9 million neurons and 14 billion synapses are lost
Recanalise n 90/7 favourable early neuro improvement outcome >260 mins 16 37% 37% 210-260 mins 15 67% 73% ( 0.07) <210 mins 15 93% 93% (0.01) Mazighi et al, Stroke, 2009
stent retriever
71F, NIHSS 19 12.11 13.15 12.39 ictus 9.30am
SPEED SWIFT,TREVO - 2 RCTS USA median time to Rx 4.6 and 4.7 hours mrs 0-2 36.4% 40% STAR, TREVO EU median time to Rx 3.2 and 3.4 hours mrs 0-2 58% 55%
STAR prospective, 14 centres, 202 consecutive pts mean age 72, mean NIHSS 17, anterior circulation occlusion, Solitaire TICA 18%; M1 67%; M2 14% 59% IV TPA treated within 8 hours; median time from ictus to groin puncture 238 mins procedure time 29+/-27 mins balloon guide catheter, flow reversal mandatory TICI 2b/3 79% mrs 0-2 58% mortality 7% SICH 1.5% good collaterals correlate with good outcome p=0.034 Perreira et al, Stroke 2013, 44, 2802-2807
74M ictus 12.40 NIHSS 21
15.34
ADAPT - a direct aspiration first pass technique 37 consecutive pts (39-90 years old) (4 month study period) mean NIHSS 16.3 (5-30) M1 17; TICA 7; basilar 7; M2 5; M3 1; ADAPT alone successful in 75% flexible large bore catheter to thrombus. Aspiration with 20 or 60 ml syringe or Penumbra aspiration pump. Engage catheter in thrombus, then slowly withdraw with suction 9 required addition of stent retriever mean time from groin puncture to TICI 2b/3 28mins TICI 2b/3 in 100% TICI 3 in 65% 1 procedural complication (asymptomatic small SAH) 2 SICH mean NIHSS 4.2 at discharge (24pts (65%) 5 or below) 5 deaths Turk et al, JNIS 2014, 231-237
S BG rin g Sp 65M, NIHSS 22 on f C ce er en 15 20
Souza et al AJNR, 2012, 33, 1331-1336 0 1 2 3 4 100% bad outcome
105 consecutive pts, IV TPA within 3 hours median NIHSS 13 28% 18% 20% 29% 2% 0 1 2 3 4 Saarinen et al AJNR, 2014
distal clot distal M1, M2, M3 good collaterals Souza 2-4
72M, NIHSS 13-18 ictus 10.30am normal parenchyma
rin g C on f er en ce 20 15 IV TPA running S Sp 12.30 BG TICI 2 12.50 1.30pm
NIHSS 1
67M ;NIHSS 23 ictus 7am 8.37am 8.37am
80 sec head
9.30 am 10.28am
MRCLEAN NEJM, 2015, 11-20 16 centres, Netherlands, Dec 2010 - March 2014 500 pts, proximal anterior circulation occlusion (CTA/MRA)IAT cf usual Rx - 267pts- IVTPA; 233 EVT within 6 hours NIHSS 2 -: average 17, 18; ASPECTS 9 (median) in each group. 233 IAT (38% GA), acute carotid stenting 13% Mean age 65yrs: range 23-96 yrs 445 pts IV TPA before randomization.time ictus to random 196-204 mins Stentretrievers in 97% Independence in 32.6% cf 19.1% ; infarct vol at 7 days 49 cf 80ml No difference in mortality (7days: 12% each gp; 19% at 30) or SICH (18%: 17%) IAT usual ICA/M1 25% 28% M1 66% 62% M2 8% 8% A1/A2 32% 26% Time ictus to groin puncture 260 minutes (median) TICI 2b/3 in 59% FU CTA /MRA 24 hours - no occlusion in 75% cf 33%
EXTEND IA NEJM 2015 IV TPA within 4.5 hours cf EVT stent retriever 70 pts enrolled; 35 each arm; stopped prematurely ICA or MCA occlusion CTP ischaemic core <70 ml. EVT within 6 hours Ischaemic core at presentation 19.6 +/- 17.4 ml Perfusion volume at presentation 116 +/- 48ml IV TPA Median NIHSS 13 17 18.9 +/- 18.5ml 103 +/- 39ml IV +EVT ICA 31% 31% M1 51% 57% M2 17% 11% Median time ictus to groin puncture Median time ictus to TICI 2b/3 TICI 2b/3 in 86% 210 mins 248 mins 90 day mrs 0-2 40% 71% p=0.01 No significant difference in mortality and SICH; 12% GA. NNT 3
SWIFT PRIME, NEJM 2015 Stopped prematurely after 196 pts, 39 centres All had IV TPA within 4.5 hours, NIHSS 8-29 (11O 17+) 83 70+ YEARS OLD LVO anterior circulation ASPECTS > 6; CT EIC < 1/3 MCA territory EVT within 6 hours; 88% complete reperfusion mrs 0-2 at 90 days 60.2% EVT cf 35.5% IVT p<0.001 NNT 4 SICH 0% cf 3% (IV) Mortality at 90 days 9.2% cf 12.4% (IV) Ictus to arterial puncture was 165-275 min (IQR) Ictus to first deployment of Solitaire 190-300 min (IQR)
REVASCAT NEJM 2015 206 pts within 8 hours, 4 centres in Spain, halted early because of other trials 18-80 years old, NIHSS 6+ (IQR 14-20 ; median 17) ASPECTS < 7 excluded Later 80-85 years ASPECTS 8+ IV TPA cf IV TPA and Solitaire, anterior circulation LVO 6.7% GA Wait 30 mins for IVTPA mrs 0-2 at 90 days 44% cf 28% OR 2.0 90 day mortality 18.4% cf 15.5% SICH 2% each arm Median time from ictus to groin puncture 269mins (201-340) Median time from ictus to revascularisation 355 mins (269-430)
ESCAPE NEJM 2015 LVO anterior circulation, within 12 hours, ASPECTS 6-10; poor collaterals excluded Standard care cf thrombectomy; enrolment up to 12 hours Stopped early 49 (15.5%) randomized after 6 hours 22 centres, 316 pts; 238 received IV TPA (120 in EVT group) Median time from CT to reperfusion was 84 mins and from ictus to reperfusion, 241 mins EVT IVT Median NIHSS 16 17 ASPECTS 9 (8-10) 9(8-10) ICA + M1 27.6% 26.5% M1 or all M2 68.1% 71.4% M2 single 3.7% 2.0% 90 day mrs 0-2 53% 29.3% p<0.001 Mortality 10.4% 19% SICH 3.6% 2.7% GA 9%
MRCLEAN OR for good outcome decreasing from 3.0 at 3.5 hours ictus to reperfusion to 1.5 at 6 hours treatment effect not statistically significant if reperfusion after 6 hours 19 mins ESCAPE- 15.5% pts were treated successfully after 6 hours collaterals extending time window based on imaging
MRCLEAN 16% were 80+ years old significant benefit from EVT- similar to entire EV cohort : OR 3.24 ESCAPE, SWIFT PRIME also showed benefit for those 80+ (oldest in ESCAPE was 93!) MRCLEAN EVT beneficial with ASPECTS 5+ not 4 and below
ESO-Karolinska Stroke Update with ESMINT, ESNR mechanical thrombectomy with IV TPA within 4.5 hours, LVO, anterior circulation up to 6 hours after ictus (level of evidence A/1a) decision jointly by multidisciplinary team including stroke physician and INR, experienced centre thrombectomy by trained experienced INR large infarcts excluded
NICE HIS July, 2013 The current evidence on mechanical clot retrieval for treating acute ischaemic stroke shows that efficacy is unproven.suitability for thrombolysis can be guided by criteria used in the PISTE trial. 1.1 Patients with acute ischaemic stroke for whom thrombolysis is unsuitable/failed;.only performed with special arrangements for clinical governance, consent, audit, research 1.2 Patients with acute ischaemic stroke for whom thrombolysis is suitable:..used only in the context of research, which should in be RCTs comparing mechanical clot retrieval or the current methods of management and should report details of patient selection, timing of the intervention after onset of symptoms, the devices and techniques used, complications and functional outcomes NICE encourages clinicians to enter patients into RTs such as PISTE
?
PISTE 18 years+, eligible IV TPA within 4.5 hours LVO, NIHSS 6+ EVT must be started within 90 mins of the IV TPA; groin puncture no more than 5.5 hours post ictus; angio within 6 hours 90 day mrs 0-2 mrs 0-1, mortality, eni 8+ NIHSS or NIHSS 0,1 at 72 hours, angio patency, immediate revascularisation rate, home time, sich etc