Treating Acute Ischemic Stroke, - PowerPoint Presentation

Slide1

Treating Acute Ischemic Stroke,Can We Open Up the Time Window？

David Wang, D.O.,FAHA, FAAN

Director, OSF/INI Stroke Network, CSC at OSF SFMC

Director, Stroke Fellowship

Clinical Professor of Neurology

UICOMPSlide2

S

tages of impaired cerebral circulation

CBF indicates cerebral blood flow;

CBV, cerebral blood volume; OEF, oxygen extraction fraction; CMRO2, cerebral metabolic rate for oxygen; CVR, cerebrovascular reserve. The stages are referenced to the changes in OEF. Stage I, OEF is unchanged. Stage II, OEF begins to increase. Whether the increase is linear is unknown. Stage III, OEF declines again. Solid lines show changes that are known and dashed lines, those that are postulated.

Need to Understand This GraphicSlide3

Let Us Review the Concept of PENUMBRASlide4

Persistent Penumbra?

Darby et al, 1999Slide5

IV tPA to all comers:

Declining benefit over time.

Is It True

？

Slide6

Evidence-based Treatment Time Window for Acute Ischemic Stroke

< 3

hrs

： IV tPA 0.9mg/kg 3-4.5 hrs: IV tPA 0.9mg/kg+4contraindications, 0.6 mg/kg< 6

hrs

:

IV tPA 0.9 mg/kg + IA

thrombectommySlide7

Let us exam the treatment window of<4.5 hours firstSlide8

IV tPA NNTB and NNTH within 3 hours and 3-4.5 hours

Saver et al Stroke 2009;40:2433-37

Number of Patients to be Benefited (NNTB) and or Harmed (NNTH) Per 100 Patients Treated With Intravenous TPA in Different Time Windows

1–3 Hours

3–4.5 Hours

NINDS tPA Trials

ECASS 3 Trial

Benefit per 100 32.3 16.4

Harm per 100 3.3 2.7

NNTB = 6.1

NNTH = 37.5Slide9

Treatment window of < 6 hoursWhat can we do?Slide10

IV TPA plus IA

Thrombectomy

，

<6 hour or <12 hour windowSlide11

7 bridging trials bring us these points

Patient selection is important and Use imaging to select pts

Treatment window

<6hrs or <12 hrsTreat FAST!Control group: ALL had IV TPATreatment group: IV TPA+IA thrombectomyIA thrombectomy used stent assisted clot retriever

Benefit: NNT: 1 in every 2-4

pts

treatedSlide12

Effectiveness of IV TPA+IA Thrombectomy Further Confirmed

Trials

90d mRS 0

-

2

Mortality

TICI 2b-3

Control

IA

Control

IA

IAMR CLEAN19%33%22％21％

59%

ESCAPE

29%53%19％

10

％

72%

EXTEND-IA

40%

71%

20

％

9

％

86%

SWIFT PRIME

36%60%12％9％88%REVASCAT28%44%16％18％66%THERAPY30.4%38%

THRACE

42.1%

54.2%

13.1%

12.5%

EAST

28.6%

53%

4.4%

8.3%

90.4%Slide13

Treated >5.5 hours in ESCAPE Trial

59/315 subjects (33 in the intervention group and 26 in the control group) were randomized in the ESCAPE trial 5.5 hours after last seen normal

Favorable outcome seen across all clinical outcomes in the extended time window (absolute risk difference of 19.3% for

mRS 0-2 at 90 days). There were more asymptomatic intracerebral hemorrhage events within the intervention arm (48.5% vs. 11.5% p=0.004) but no difference in symptomatic ICH.Slide14

Between 3-8 hrs, any other options?Slide15

Two mechanical devices have been approved by FDA to remove or retrieve thrombus in acute ischemic stroke:

MERCI

：

Not used anymorePenumbra system: In use

Between 3-8 hrs, any other options?Slide16
Slide17
Slide18
Slide19
Slide20
Slide21
Slide22
Slide23

IV TPA >8 hours?Slide24

Can IV TPA be given to patients with stroke upon waking up?

NIHSS≥6

Age:18

－

85

Onset to treatment <8

hours

ICA,MCA M1 M2

occlusionmRS 0－2 prior to randomizationIV tPA allowedIdentifying Penumbra by DWI/PWI mismatch did not show better result with IA therapyIA thrombectomy showed no additional benefit than IV T-PASlide25

MR WITNESS

~15-30% of stroke pts awaken with deficits or have unclear onset times

DWI positive FLAIR negative pattern on MRSlide26

80 pt enrolled with 71% wakeup strokeMedian NIHSS 7.5(IQR 4.3-13.8)Slide27
Slide28
Slide29
Slide30

Beyond 12 hrs? Possible?Slide31

Persistent Penumbra?

Darby et al, 1999Slide32

Pre DAWN trial in 2009:Endovascular therapy in late presenting stroke

patients (>8 h) is a safe therapy in wake up stroke

Occlusion sites were: M1 MCA (94/49%), M2 MCA (19/10%), ICA terminus (43/22%), tandem ICA origin/MCA (25/13%), tandem ICA origin/ ICA terminus (12/6%)

93 patients, mean age of 64.4 (median 67; range 19–91)

Mean NIHSS 15

Mean time to treatment was 16.3 613 h (median 12.4; range 8–111).

Intra-arterial

thrombolytics

in 92/193 (48%), Merci Retriever in 110/193(57%) and other mechanical modalities in 56/193 (29%).

Successful (TIMI 2 or 3) recanalization was achieved in 141/193 (73%) cases.

90 day outcomes MRS 2-3in 69 (45.7%) and 92 (60.9%) ICH was 20/193 (10.4%). Mortality rate was 22.2% (42/189).Age (OR 0.96; 95% CI 0.93 to 0.99, p 50.026), time to treatment (OR 1.11; 95% CI 1.01 to 1.21, p 50.019) and successful recanalization (OR 3.21; 95% CI 1.21 to 8.51, p 50.018) were significantly associated with favorable outcomes.Slide33

An early end to patient enrollment in the DAWN trial Treating stroke 6 to 24 last known well

Stryker: preplanned interim review of data from the first 200 patients, which concluded that multiple

prespecified

stopping criteria were met. DSMC recommended stopping the trial.500 patients plannedMechanical thrombectomy with the Trevo Retriever plus medical management leads to superior clinical outcomes at 90 days as compared with medical management alone in acute stroke patients treated 6 to 24 hours after last seen well. Slide34
Slide35

Conclusions

Under the imaging guidance, the future of acute ischemic treatment is

likely to have longer windows and multiple treatment modalities used together:

IV thrombolysis+IA thrombectomy+

Anticoagulants+

hypothermia+

neuronal protecting agents Slide36

Conclusions

Identify patient early

The earlier, the more options we have

Using imaging to identify those outside the windowStronger and better thrombolytics may be used in evolving lacunar syndrome in an even later time