Current Status and Future Directions Tudor G Jovin MD Associate Professor of Neurology and Neurosurgery Director UPMC Stroke Institute Director UPMC Center for Neuroendovascular Therapy University of Pittsburgh Medical Center ID: 807536
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Slide1
ACUTE ISCHEMIC STROKE THERAPYCurrent Status and Future Directions
Tudor G. Jovin, M.D.
Associate Professor of Neurology and Neurosurgery
Director, UPMC Stroke Institute
Director, UPMC Center for Neuroendovascular Therapy
University of Pittsburgh Medical Center
Slide2DISCLOSURES Consultant/Advisory Board: Ownership Interest: Silk Road- modest
Slide3LARGE VESSEL OCCLUSION STROKE CARRIES THE WORST PROGNOSIS
Slide4NATURAL HISTORY OF LARGE VESSEL INTRACRANIAL OCCLUSION STROKECONTROL
Arm Estimates*
Study
ICA/M1
mRS
0-2
(independent level
of functioning)
Germans
Trias
Barcelona
6-24 hr
17.4%
STOP
Stroke
0-8 hr
18.4%
FIRST
0-8 hr
20.4%
PROACT II
0-6 hr
(+ M2)
25%
Slide5ACUTE LARGE VESSEL STROKE- NATURAL HISTORYSENTIS - CONTROL GROUP
MR RESCUE - CONTROL GROUP
N=54
Occlusion location: ICA (13%), M1(72%), M2 (15%)
Median NIHSS: 16 (penumbral), 20.5 (non-penumbral)
Median age: 66 (penumbral), 67 (non-penumbral)
mRS
0-2 : 23 % (penumbral), 10% (non-penumbral)
Mortality: 21% (penumbral), 30% (non-penumbral
)
Kidwell et al., NEJM 2013
Slide6ACUTE LARGE VESSEL STROKE- OUTCOMES IN iv t-PA TREATED PATIENTS
Endovascular
IV tPA Only
Baseline Primary Occlusion Vessel Category
Subjects with Baseline CTA
mRS 0-2
Subjects with 24 hour* CTA
Percent Recanalized** of Subjects with 24 hour* CTA
Subjects with Baseline CTA
mRS 0-2
Subjects with 24 hour* CTA
Percent Recanalized** of Subjects with 24 hour* CTA
All
190
44.74%
147
85.71%
92
38.04%
6960.87%ICA- T/L3923.08%2382.61%195.26%1428.57%M110248.04%8585.88%4751.06%3467.65%Vertebral & Basilar333.33%366.67%10.00%10.00%All Proximal (ICA, M1, Basilar)15041.33%11584.35%7038.57%5255.77%
Demchuk, ISC 2013
CLOTBUST - iv t-PA control group M1+M2 : 37% mRS 0-2
- iv –tPA + TCD M1+M2: 51% mRS 0-2
Alexandrov, NEJM 2004
Slide7RECANALIZATION AND OUTCOMES IN ACUTE STROKE
Stroke
2007 Mar;38(3): 967-73
Slide8R
Yoo AJ et al. ISC, 2013
Zaidi
et al., Stroke 2013
RELATIONSHIP BETWEEN RECANALIZATION, INFARCT VOLUME AND CLINCAL OUTCOMES
Slide9PATIENTS WITH M1 OCCLUSION (N=178): MULTIVARIATE ANALYSIS PREDICTORS OF GOOD OUTCOME
Odds Ratio
p value
95% CI
Age
0.91
<0.001
0.87-0.94
Follow-up DWI Volume
0.97
<0.001
0.97-0.99
Zaidi et al, Stroke 2012
Slide10Yoo et al, Stroke 2012
INFARCT VOLUMES AND OUTCOMES
Slide11THROMBOLYTIC THERAPY FOR STROKENINDS - % With Favorable Outcome at 3 Months
NEJM 1995;333:1581-1587
Slide12Minutes Stroke Onset To Start of Treatment
60
70
80
90
1
00
110
120
130
140
150
160
170
180
Odds Ratio
Favorable Outcome
0
1
2
345678mBenefit for rt-PANo Benefit for rt-PAMarler et. al., Stroke 1999;30:244Time Is Brain: Effects of tPA vs Time
Slide13Odds Ratios for Favorable Outcome Pooled tPA Analysis
Time
Odds Ratio
95% C.I
0-90 2.8 1.8, 4.5
91-180 1.5 1.1, 2.1
181-270 1.4 1.1, 1.9
271-360 1.2 0.9, 1.5
Lancet 2004;363:768-774
Slide14ECASS IIIRandomized double blind – IV tPA v. placebo821 pts 3 - 4.5 hrs after stroke; 130 sites in 19 countriesAge 18 – 80 NIHSS
< 25Excluded pts on anticoagulants, prior stroke and diabetes
Primary outcome – mRS 0-1 at 90 days
tPA
Placebo
Odds Ratio
p Value
Pts
418
403
Median
NIHSS
9
10
mRS
0-1
52.4%
45.2%
1.34 (1.02-1.76)
0.04
Sx Hem2.4%0.2%9.85 (1.26-77.32)0.008Mortality7.7%8.4%0.90 (0.54-1.49)0.68Hacke et al. NEJM 2008
Slide15Limitations of IV Therapy3-4.5 hour time windowLess effective for large artery occlusionEarly reocclusion in 20 – 30%Contraindications such as recent surgery or invasive procedure
Single modality treatment
Slide16IV TPA Treatment CriteriaMust have a witnessed onsetNIH stroke scale score > 4 or cortical findings (aphasia, visual loss)Negative CT scan for hemorrhage/early ischemic changesBlood pressure control
Normal coags/PLT countNo active bleeding or recent trauma, stroke, surgery
Slide17IV TPA Treatment CriteriaBlood pressure < 185 SBP and <110 DBPPlatelet count > 100kNormal PTTINR < 1.7 (for patients treated with coumadin)No Dabigatran (Pradaxa) within 48 hrs
Slide18Pretreatment issuesRule out hypoglycemia as causeExpedite stat non-contrasted CT scan of brain – door to CT target < 20 minExpedite stat labs Perform NIH stroke scale and document
Slide19ED Nursing CareEstablish IV access – 2 peripheral IV’s IF NOT TIME CONSUMING !!!Document time last known well and neurologic exam - NIHSSContinuous Cardiac monitoring with frequent BP, SaO2 monitoring
If suspect need for Foley catheter, insert prior to start of IV tpaNo invasive procedures after TPA started
Slide20Care during and post tpaQ 15 minute vital signs and NIHSS for first 2hours, then q 30 min X 6 and then hourlyNo anticoagulants or antiplatelet agents for 24 hrsAdmit to ICU Repeat CT scan in 24 hrsNotify MD if worsening of
neuro exam, c/o headache, or bleeding concern
Slide21Neurologic Clinical DeclineMay be as mild as decline in level of consciousnessSevere headache Nausea/vomitingWorsening of clinical deficitPupillary changes (dilation)
Decorticate or decerebrate posturing
Slide22Treatment of Neurological declineStat non contrasted CT scan of brain – if negative for blood CTA to r/o reocclusion If hemorrhage – reverse t-PA with cryoprecipitate and FFP
If seizure – anticonvulsantsStat neurosurgery notificationSurgical decompression
If hemorrhagic conversion with mass effectIf meanigful neurological recovery is deemed possible and after discussion with family
Slide23BP Management in the Acute Phase - IschemicIf treated with thrombolytics – must aggressively control BP for first 24 hrs to reduce risk of hemorrhagic conversionAgents to consider
Beta Blockers – IV LabetelolCa Channel blockers – IV Nicardipine/
ClevedipineAvoid Nipride if possible
Slide24General Management of Acute StrokeBody position
Maintain airwayOxygen
BP managementFluid managementGlucose
Temperature
Antithrombotic therapy
Slide25PRE-TREATMENT ISCHEMIC CORE A POWERFUL DETERMINANT OF OUTCOME IN ACUTE STROKE
CT based (ASPECTS), Hill et al., Stroke 2003
CTP based (CBV), Lev at al., Stroke 2001
Xenon-CT-CBF based (core voxels), Jovin et al, Stroke 2003
MRI based (DWI), Yoo et al., Stroke 2009 (DWI cutoff of 70 cc’s predicts poor outcome)
MRI based (DWI), Parsons et. al, Journal Cereb Blood Metab 2010 (DWI cut off 25 cc)
Slide26Time to Reperfusion vs. Outcome
Khatri et al, Neurology 2009
Khatri et al, ISC 2013
IMS I & II (n=54)
IMS III (n=182)
Every 30 minute delay in reperfusion is associated with a
10% relative reduction in probability of
good clinical outcome (mRS 0-2).
Khatri et al, ISC 2013
Slide27RELATIONSHIP BETWEEN TIME-TO-TREATMENT AND OUTCOME BEYOND THE 3 HOUR TIME WINDOWJovin, ISC 2010
ENDOVASCULAR STROKE STUDIES ENROLLING PATIENTS BEYOND 3 HOURS (PROACT II
1
, MERCI/MULTI MERCI
2
, SWIFT
3
, TREVO 2
4
) FAILED TO SHOW A SIGNIFICANT ASSOCIATION BETWEEN TIME-TO-TREATMENT AND OUTCOME INDICATING THAT OTHER FACTORS MAY BE STRONGER PREDICTORS OF OUTCOME THAN TIME
MERCI Registry (n=675)
1
Wechsler et al., Stroke 2003,
2
Nogueira et al., Stroke 2009,
3
Liebeskind et al. ISC 2013,
4
Liebeskind et. al., ISC 2013,
Slide28“Time is Brain”
TIME VS PHYSIOLOGY BASED SELECTION FOR REPERFUSION THERAPY
Slide29SERIAL MRI’S (CORONAL SECTIONS) AT THREE LEVELS IN THE BRAIN DEPICTING THE APPARENT DIFFUSION COEFFICIENT OF WATER (ADC) (MARKED BY THE BLUE COLOUR) DEMONSTRATING THE TIME-DEPENDENT GROWTH OF THE ISCHEMIC CORE.
Hossman et al., Cell Mol Neurobiol, 2006
PROGRESSIVE GROWTH OF CORE IN MCA OCCLUSION
Slide30Courtesy of Greg Albers, MD
RATE OF INFARCT PROGRESSION
Slide31A total of 237 patients were treated in 12 centers from March 1998 to Oct 2009
Mean age: 63.71+/-15.75 years (median, 66; range, 19-91)
116 (48.95%) males
NIHSS:
Mean +/- SD: 15+/-5.4
Median, 15; IQR, 12-19
Time from last seen well to treatment (hours):
Mean +/- SD: 14+/-11
Median, 12.2; IQR, 9.7-16.4
Range, 8 - 111 hours
Endovascular Therapy for Anterior Circulation Stroke Presenting Beyond 8 Hours
Multi-center Experience
Jovin et al., Stroke 2011
Slide32Occlusion sites:
MCA-M1: 48.5% (115/237)
MCA-M2: 10.5% (25/237)
ICA-T: 20% (47/237)
Tandem cICA + MCA: 15.61% (37/208)
Tandem cICA + ICA-T: 5.49% (13/237)
Treatment modalities
IA thrombolytics: 109/237 (46%)
MERCI device: 147/237 (62.03%)
Other mechanical modalities: 85/237 (35.86%)
Successful (TIMI 2-3) recanalization:73.84 % (175/237)
Good outcomes (mRS ≤2): 44.64% - 100/224 available datasets
sICH rate: 8.86% (28/237) [vs. 10% in PROACT-II]
Mortality: 21% (51/237) [vs. 44% in MERCI]
Jovin et al., Stroke 2011
Endovascular Therapy for Anterior Circulation Stroke Presenting Beyond 8 Hours
Multi-center Experience
Slide33Predictors of Good Outcome at 90-Days on Multivariate Analysis:
Variable
90-Day mRS ≤2
Odds Ratio (95% CI)
P
Value
Age
0.95 (0.93-0.97)
<0.000
TIMI 2-3 Flow
5.29 (2.35-11.8)
< 0.000
NIHSS
0.93 (.86-0.97)
0.006
Jovin et al., Stroke (2011)
Endovascular Therapy for Anterior Circulation Stroke Presenting Beyond 8 Hours
Multi-center Experience
Slide34Tx ≤6 hrs
N= 36
Tx >6 hrs
N=42
P-value
Mean (SD) age, years
64 (19)
69 (13)
0.24
Median (IQR) NIHSS
16 (11-21)
14 (10-20)
0.21
Percent pretreated with IV tPA
67%
29%
0.001
Median (IQR) DWI volume, ml
12 (8-25)
14 (5-26)0.76Median (IQR) PWI (Tmax>6s) volume, ml90 (63-107)70 (45-110)0.16Median time (IQR) symptom onset to start of endovascular treatment, hrs4.8 (3.4-5.4)7.9 (6.5-9.4)<0.001DEFUSE 2: Baseline Characteristics Target Mismatch patients by Time to TreatmentAlbers G, ESC 2012
Slide35Reperfusion
N=22
<
6 hours
No reperfusion
N=14
DEFUSE 2 TARGET MISMATCH:
OUTCOMES BY TIME AND REPERFUSION
Reperfusion
N=24
> 6 hours
No reperfusion
N=18
Slide36Defuse II CASE EXAMPLE63 year old manHistory of HTN, H.Chol and CAD
Baseline NIHSS 12Left ICA terminus occlusion9.5 hours from onset to groin puncture
Conscious sedation
Slide37Baseline MRI
DEFUSE protocol
Slide38Baseline Angiograms
ICA terminus occlusion
Slide39Collaterals
Slide40MANUAL ASPIRATION THROMBECTOMY + MERCI
Slide41Final Angiogram
Slide42Follow-up MRI
Small BG infarct
Slide43Clinical Outcome & SummaryDischarged to home on day 2.NIHSS 2 at the time of discharge
Slide44SUMMARY OF RECENTLY COMPLETED RANDOMIZED TRIALS
Time window
# of patients enrolled
Good Outcomes
(mRS 0-2)
Mortality
sICH
Reperfusion
TICI 2-3/2b-3
IMS3
1
3 h
656
IV only
222
38.7%*
21.6%*
5.9%*
IV + IA
434
40.8%*19.1%*6.2%*81%/44%SYNTHESIS EXPANSION 24.5 h362IV only18146%**6%**6%**IA only18142%**8%**6%**MR RESCUE 38 h118Mismatch3223%***
21%***
6%***
Penumbral/IA
32
14%***
18%***
9%***
59%/24%
No mismatch
19
10%***
30%***
0%***
Non-penumbral/IA
30
9%***
20%***
0%***
77%/27%
1
Broderick et al, NEJM 2013,
2
Ciccone et al. NEJM 2013,
3
Kidwell et al. NEJM 2013
* p=ns,
**
p=ns,
***
p=ns
Slide45SUMMARY OF RECENTLY COMPLETED RANDOMIZED TRIALS: KEY ISSUES
IMS3
MR RESCUE
SYNTHESIS EXPANSION
Proof of vessel occlusion
No
Yes
No
Poor recanalization rates
44% TICI 2b/3
27% TICI 2b/3
No info
Large infarct at baseline
40% pts with ASPECTS < 8
Median core volume 60 cc
No info
Long time to treatment
81 min (mean) iv t-PA to groin
2hrs/4 min(mean) imaging to groin
iv 1 hr earlier than ia
High rate of good outcomes with iv t-PA38% mRS (0-2)No info 46.4% mRS (0-2)Slow enrollment (lack of equipoise ??)656 pts/6 years/58 centers127pts/7years/ 22 centers362 pts/4years/24 centers
Slide46IMS III- Subject AccountabilityRandomized (n=656)
IV only (n=222
)
Endovascular (n=434)
Did not receive
angiogram (n=11)
Received angiogram (n=423*)
Endovascular therapy not administered (n=89
)
Endovascular therapy administered (n=334
)
Endovascular therapy
administered (n=3)
Received IV tPA only (n=219)
Tomsick T, et al ISC 2013
Slide47IMS III Trial Primary ResultALL
IV/Endovascular (n=434)
IV rtPA Only(n=222)
mRS
0-2 (%)
177
(
40.8%
)
86
(
38.7%
)
CMH p-value 0.70
(adjusted for NIHSS strata)
Broderick J et al, NEJM 2013
Slide48IMS III- Descriptive CharacteristicsTime Parameters
Time from Symptom Onset to IA End/Reperfusion
Mean (SD) = 325 (±52) min
Range 180-418 min
Khatri et al, ISC 2013
Slide49IMSIII- IMPORTANCE OF TIME
Slide50Time to Reperfusion vs. Outcome
Khatri et al, Neurology 2009
Khatri et al, ISC 2013
IMS I & II (n=54)
IMS III (n=182)
Every 30 minute delay in reperfusion is associated with a
10% relative reduction in probability of
good clinical outcome (mRS 0-2).
Khatri et al, ISC 2013
Slide51Time to Reperfusion vs. Outcome in IMS3
Khatri
et al., Lancet
Neurol
2014
Slide52STEPS FROM DOOR-TO-REPERFUSION: PUBLISHED DATA (N=50)
Costalat et al., Stroke 2011
216 min 3.5 hrs
Slide53Miley et al, JNI 2009
Slide54IMS 3 TIME INTERVALS
Goyal
M et. al., Circulation 2014
Slide55IMSIII- IMPORTANCE OF RECANALIZATION
Slide56IMS 3 Final DSA TICI and 90 d mRS < 2
P<0.001
Slide57IMSIII- IMPORTANCE OF BASELINE IMAGING(ASPECTS SCORE)
Slide58ASPECTS predicts outcome
ASPECTS 8-10
ASPECTS 0-7
RR (CI
99
)
ASPECTS 0-4
ITT population
N= 378
N= 278
N= 92
mRS 0-2 at 90d %,n
49% (187)
27% (76)
1.8
(1.4-2.2)
21% (19) mRS 0-1 at 90d %,n34% (130)18% (50)1.9 (1.4-2.5)12% (11) NIHSS 0-1 at 90d, % n33% (123)17% (47)1.9 (1.4-2.6)7% (6)Onset-IV tPA time <= 120 min AND baseline ICA and /or M1-MCA occlusion on CTAN=57N=65 N=17 mRS 0-2 at 90d %,n61% (35)25% (16)2.5 (1.5-4.0)12% (2) mRS 0-1 at 90d %,n44% (25)17% (11)2.6 (1.4-4.8)12% (2) NIHSS 0-1 at 90d, % n44% (25)20% (13)2.2 (1.2-3.9)6% (1)Hill et all ISC 2013
Slide59IMSIII- IMPORTANCE OF BASELINE IMAGING(VESSEL STATUS - CTA)
Slide6090-Day mRS Distribution, Baseline CTA Occlusion Present
van Elteren test p-value 0.0114
Demchuk
et
al, Radiology 2014
Slide61Pre-specified Baseline Proximal Occlusions
Endovascular
IV
tPA
Only
Baseline Primary Occlusion Vessel Category
Subjects with Baseline CTA
mRS
0-2
Subjects with 24 hour* CTA
Percent
Recanalized
** of Subjects with 24 hour* CTA
Subjects with Baseline CTA
mRS
0-2
Subjects with 24 hour* CTA
Percent
Recanalized
** of Subjects with 24 hour* CTAAll19044.74%14785.71%9238.04%6960.87%All Proximal (ICA, M1, Basilar)15041.33%11584.35%7038.57%5255.77% Chi-square pvalue <0.0001 (24h recan) Chi-square pvalue NS (mRS 0-2)Demchuk et al, Radiology 2014
Slide62Endovascular
IV
tPA
Only
Baseline Primary Occlusion Vessel Category
Subjects with Baseline CTA
mRS
0-2
Subjects with 24 hour* CTA
Percent
Recanalized
** of Subjects with 24 hour* CTA
Subjects with Baseline CTA
mRS
0-2
Subjects with 24 hour* CTA
Percent
Recanalized
** of Subjects with 24 hour* CTAAll18944.44%14686.30%9138.46%6864.71%ICA-T/L3923.08%2382.61%195.26%1428.57%Tandem M1 with ICAo742.86%785.71%40.00%425.00%Combined4626.09%*3083.33%**234.35%*1827.78%**IMS III- Post-hoc analysis: Carotid T/L or Tandem ICA+M1*Fisher p value 0.0471 (% mRS)**Chi-square p-value 0.0001 (% recanalized) Demchuk et al , Radiology 2014
Slide63IMSIII- IMPORTANCE OF TECHNOLOGICAL ADVANCES
Slide64REVASCULARIZATION RATES AND OUTCOMES IN IMS
TICI=0
TICI=1
TICI=2a
TICI=2b
TICI=3
n= 32
n= 16
n= 67
n= 80
n= 5
% 90 Day
mRS
0-2
3.1%
12.5%
19.4%
46.3%
80%
6.3%35.5%p < .000113.9%48.2%p < .0001Tomsick T, et al ISC 2013
Slide65Solitaire (eV3)
Trevo (Concentric Medical)
STENTRIEVERS: A REVOLUTION IN ENDOVASCUALR ACUTE STROKE TREATMENT
Slide66Endpoint
Trevo2
Trevo
(n=88)
Trevo2 Merci (n=90)
Trevo2
p-value
(n=178)
SWIFT Solitaire
(n=58)
SWIFT Merci
(n=55)
SWIFT
p-value
(n=113)
Successful
Recanalization
*
86.4% (76/88
)
TICI 2b-367.8%60.0% (54/ 90)TICI 2b-343.4% < 0.000168.5% (37/54)30.2% (16/53)< 0.0001mRS 0-2 at 90d**40.0% (34/85)21.8% (19/87)0.013036.4% (20/55)29.2% (14/48)0.5300mRS ≥ 2, OR ↓NIHSS ≥ 10 points, OR return to baseline mRS at 90 days52.9%(45/85)42.5%(37/87)0.221858.2% (32/55) 33.3% (16/48) 0.0172Mortality at 90-days33.0% (29/88)23.6% (21/89)0.184517.2% (10/58)38.2% (21/55)0.0196mRS 0-3 at 90d49.4% (42/85) 37.9% (33/87) 0.166356.4%(31/55)37.4%(18/48)0.0752SICH***6.8%(6/ 88) 8.9% (8/ 90) 0.78201.7% (1/58)10.9% (6/55)0.0566 Saver J et al. Lancet, Aug 2012, Nogueira RG et al., Lancet Aug 2012 SWIFT & TREVO 2: 2 RCTs - Stent-Retrievers > Merci
Slide67Slide68STENTRIEVER + MANUAL ASPIRATION
Slide69CONCLUSIONSSecondary analyses from IMS3 reveal important information that help explain the overall findingsTrends toward benefit in patients with baseline CTA vs no baseline CTA Strong trend towards benefit in patients with ICA occlusionHigh recanalization rates at 24 hours with iv t-PA (except ICAO)Baseline ASPECTS predictive of outcome in general but not in iv vs ia
Recanalizaton strongly predicts outcomes Fairly low TICI 2b/3 recanalization rates across all treatment modalities in ia group (SOLITAIRE used only in 3 cases)Importance of time to reperfusion cannot be overemphasized
Slide70RECENTLY COMPLETED SINGLE ARM STUDIESSTAR: prospective, single arm, core lab reviewedEndovascular treatment with Solitaire FR for MCA/ICA occlusions with NIHSS 8-30 presenting within 8 hours of symptoms onset
Core based imaging selection (CT ASPECTS ≥ 7, MR ASPECTS ≥ 6)
Median age: 72
Median NIHSS: 17
TICI 2b/3: 85%
Median time from onset to groin puncture: 4 hours
Median procedure duration: 32 minutes
Favorable outcomes (mRS 0-2): 57.9%
sICH: 1.5%
Mortality: 7%
Pereira et al., Stroke 2013
Slide71354
patients were enrolled in NASA
156
NASA vs.
434
IMS-III IV+IA (mainly IA
tPA
/Merci; <0.1%
Stentriever
) vs.
222
IMS-III IV
tPA
Baseline variables were not different (NIHSS was higher in NIMG 19
vs
17 in IMS-III IV+IA and 18 in IMS-III IV).
Good outcome
: NASA
51.5%
vs. 40.8% in IMS-III IV+IA and 38.7% in IMS-III IVMortality: NASA 24.6% vs. 19.1% in IMS-III IV+IA and 21.6% in IMS-III IV.mTICI 2b-3: NASA 70%; vs 40% in IMS-III IV+IA . mTICI 3: NASA 41% vs 2% in IMS-III IV+IA.IMS3-Like Subgroup Analysis of the North American Solitaire Acute Stroke RegistryZaidat OO, AAN 2013
Slide72WHATEVER WE THINK ……
Slide73BOTTOM LINE: WE NEED RANDOMIZED DATALegitimize the procedureChange IA therapy for stroke from optional to mandatory (standard of care)
Change organization of stroke centers by levels of care
Obtain resources from government/ insurances Raise awareness about natural history of stroke due to LVO
Slide74YES
better systems of care (workflow)
better technology better selection methods
Slide75ONGOING OR SOON TO BE INITIATED RANDOMIZED TRIALS
STUDY NAME
Time window
(hours)
Proof of arterial occlusion
Planned sample size
Treatment tested
ESCAPE (CA + US)
0 -12
YES
350
Endovasc
vs. Standard (
includes
iv
rt
-PA)
BASICS (NE)
0 - 6
YES750 IV-rtPA vs. Bridging (Basilar artery only) THRACE(FR)0 - 4YES480 IV-rtPA vs. bridging PISTE (UK)0 - 5.5 YES800 IV-rtPA vs. bridging MR CLEAN (NE)0 - 6YES500Endovasc vs. Standard (includes iv rt-PA) THERAPY (US)0 - 8YES692 IV-rtPA vs. bridging REVASCAT (SP)0 - 8YES690 Solitaire embolectomy vs. standard (includes iv rt-PA)EXTEND – IA (AUS)0-6YES100 IV-rtPA vs. bridgingSWIFT-PRIME (US)0 - 8YES833 IV-rtPA vs. bridging DAWN (US)6 - 24YES600 Wake-up or late (<24h): Endovasc. vs. standard
Slide76Future challangesGeneration of class I evidence for clincal efficacy (randomized controlled studies)
Optimization of imaging selection tools
Radical reduction in door-to-groin and groin to reperfusion timesTurning “fast progressors ” into “slow progressors ” (neuroprotectant drugs, hypothermia, collateral augmentation strategies)
Slide77Thank you for your attention !!!!