New guidelines for endovascular therapy with emphasis on Class I level a

New Class I level A recommendations for endovascular therapy

 

(1) pre-stroke modified Rankin Score (mRS 0-1)
(2) acute ischemic stroke receiving IV rtPA within 4.5 hours of onset according to guidelines from professional medical societies,
(3) causative occlusion of the internal carotid artery or proximal middle cerebral artery (M1),
(4) age 18 years and over,
(5) National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater,
(6) Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of6 or greater, and
(7) treatment can be initiated (groin puncture) within 6 hours of symptom onset

 

"If endovascular therapy is contemplated, a noninvasive intracranial vascular study is strongly recommended during the initial imaging evaluation of the acute stroke patient but should not delay IV rtPA if indicated. For patients who qualify for IV rtPA according to guidelines from professional medical societies, initiating IV rtPA before non-invasive vascular imaging is recommended for patients who have not had non-invasive vascular imaging as part of their initial imaging assessment for stroke. Non-invasive intracranial vascular imaging should then be obtained as quickly as possible"  (Class I, Level A recommendation)

 

"Regional systems of stroke care should be developed. These should consist of consisting of:
Health care facilities that provide initial emergency care including administration of IV rtPA, including PSCs, CSCs and other facilities
Centers capable of performing endovascular stroke treatment with comprehensive peri-procedural care, including CSC and other health care facilities, to which rapid transport can be arranged when appropriate"

Class 1 Level A evidence

 

When treatment is initiated beyond 6 hours from symptom onset, the benefits of endovascular therapy are uncertain for patients with acute ischemic stroke who have causative occlusion of the internal carotid artery or proximal middle cerebral artery (M1).Additional randomized trial data are needed

 

"It might be reasonable to favor conscious sedation over general anesthesia during endovascular therapy for acute ischemic stroke. However, the ultimate selection of anesthetic technique during endovascular therapy for acute ischemic stroke should be individualized based on patient risk factors, tolerance of the procedure, and other clinical characteristics. Randomized trial data are needed.  (RATES ONLY LEVEL 2B, CLASS C RECOMMENDATION)" (Dr. Tsappidi previously outlined case for anesthesia and our policy is that the interventionist can decide whether to use).

REVASCAT

206 patients with acute ischemic stroke
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PROBE design
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NIHSS ≥ 6
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Intracranial ICA or M1 occlusion by CTA, MRA or DSA.
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Patients who had received IV rtPA were eligible if there was no significant neurological improvement (criteria specified in the protocol) at 30 minutes post initiation of the infusion and vascular imaging at this time confirmed an eligible occlusion.
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Groin puncture had to be possible within 8 hours of stroke onset.
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There were exclusion criteria for coagulopathies. The main exclusion criteria on imaging were ASPECTS <7 on NECT or <6 on DWI-MRI. After the enrollment of 160 patients, the inclusion criteria were modified to include patients up to the age of 85 years (initially 80 years was maximum allowed) with an ASPECTS >8.
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Only 95% confidence intervals were reported.

 

Results:
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The primary outcome analysis showed a common odds ratio of improvement in the distribution of the modified Rankin scale score (shift analysis) favoring endovascular treatment (adjusted odds ratio 1.7, 95% CI 1.05 to 2.8).
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The proportion of patients with a mRS of 0-2 at 90 days was 43.7% in the intervention group and 28.2% in the control group (adjusted odds ratio 2.1, 95% CI 1.1 to 4.0).
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There were no significant differences in death or sICH.
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Ninety-five per cent of those in the endovascular group underwent thrombectomy.
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TICI 2b/3 recanalization was observed in 66% of the endovascular group.
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Across the pre-specified subgroups, there were no significant interactions according to NIHSS score, vessel-occlusion site, baseline ASPECTS score, administration of IV rtPA, age or time of randomization, although for the latter dichotomized at 4.5 hours, the p-value for interaction was 0.9 with the later group doing worse. No data are given for those who underwent groin puncture after 6 hours

 

COMMENT-- ALLOWED GROIN PUNCTURE UP TO 8 HOURS BUT DID NOT ANALYZE THAT GROUP, REQUIRED ASPECTS > 7, AGE UP TO 85 

EXTEND 1A

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Seventy participants who were eligible using "standard criteria" to receive IV rtPA within 4.5 hours of stroke onset were randomized in a PROBE design to receive either IV rtPA only or IV rtPA plus endovascular therapy with a stent retriever.
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Groin puncture had to be within 6 hours and endovascular treatment had to be completed within 8 hours after stroke onset.
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CT or MRI had to be performed before commencing IV rtPA. Occlusion of the ICA or of M1 or M2 on CT angiography was required. In addition, CT or MRI perfusion imaging had to show (a) mismatch ratio of greater than 1.2, and (b) absolute mismatch volume of greater than 10 mL, and (c) infarct core lesion volume of less than 70mL based on specialized software
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Exclusion criteria for coagulopathies as in SWIFT-PRIME
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The co-primary outcomes were reperfusion at 24 hours and early neurologic improvement (≥8-point reduction on the NIHSS or a score of 0 or 1 at day 3). The mRS at 90 days was a secondary outcome.

 

Results Interim Analysis:
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Trial halted showed that stopping criteria had been met.
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Occlusion sites: ICA 31%, MCA 54%
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Percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular group than in the IV rtPA group.
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Outcomes: Endovascular therapy, initiated at a median of 210 (IQR 166-251, IQR) minutes after the onset of stroke, increased early neurologic improvement at 3 days (80% vs. 37%, p=0.002).
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More patients achieved functional independence in the endovascular group (mRS 0-2, 71% vs. 40%; p=0.01).
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There were no significant differences in rates of death or sICH.
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Recanalization to TICI2b/3 was achieved in 86% of patients in the endovascular group at a median of 248 (IQR 204-277) minutes after stroke onset.

 

COMMENT---ENDOVASCULAR THERAPY 'WAS INITIATED' AT 3.5 HOURS

 

SWIFT PRIME

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Purpose:
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To determine if patients experiencing an acute ischemic stroke due to large vessel occlusion, treated with combined IV tPA and Solitaire FR within 6 hours of symptom onset, have less stroke-related disability than those patients treated with IV tPA alone.
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Methods:
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Global, multicenter, prospective, randomized, open, blinded endpoint (PROBE) IDE Study
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Intervention: IV rtPA with Solitaire FR Device
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Control: IV rtPA alone
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39 enrolling centers

 

Inclusion Criteria
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Acute ischemic stroke
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Age 18-80
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Pre-stroke mRS<1
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ASPECTS <6
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Baseline NIHSS 8-29 at time of randomization
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Initiation of IV rtPA within 4.5 hours of onset of stroke
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CTA or MRA confirmation of large vessel occlusion in ICA, M1 segment of MCA or carotid terminus
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Endovascular treatment can be initiated within 6 hours of onset of stroke symptoms and within 90 minutes from CTA/MRA to groin puncture

 

If CTA or MRA was part of local standard of care, it was performed at initial evaluation prior to commencing IV rtPA; if not, it was performed after review of the initial imaging and signing of informed consent.
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Initially, CT perfusion or multimodal MRI was required and enrollment was restricted to patients with the target mismatch profile (as assessed by specialized software) and defined as: the ischemic core lesion measured 50 mL or less, the volume of tissue with a time to maximum delay of more than 10 seconds was 100 mL or less, and the mismatch volume was at least 15 mL and the mismatch ratio was more than 1.8.
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Midway through the trial, the inclusion criteria were modified to accommodate sites with limited perfusion imaging capability. Sites with perfusion imaging were encouraged to continue to use the target mismatch criteria. Sites without perfusion imaging used ASPECTS scores (ASPECTS > 6 was required)

 

Results:
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196 patients were randomized after IV rtPA up to 6 hours from onset to groin puncture to Solitaire IA therapy or control.
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Two primary outcomes (shift analysis): mRS at 90 days (p < 0.001) and increased proportion with mRS 0-2 at 90 days -60% in the endovascular group and 35% in the rtPA alone group (risk ration 1.70, 95% CI, 1.23-2.33)
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No differences in death or symptomatic ICH (sICH)
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TICI 2b/3 recanalization: = 88% in the endovascular group.

escape TRIAL

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PROBE two-arm superiority trial of 316 patients with acute ischemic disabling stroke, NIHSS > 5, capable of being randomized up to 12 hours after onset.
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CT/CTA, NECT and CTA (multiphase): door to imaging <25 minutes
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Small infarct core (ASPECTS = 6-10 or CTP)
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Occluded proximal artery in anterior circulation, MCA -M1 or 2 or more M2, moderate to good collaterals(filling of 50% of the pial MCA on CTA)
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1:1 randomization of 58 patients who received IV rtPA within 4.5 hours
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Receive guideline-based care alone or guideline-based care plus endovascular treatment with the use of available thrombectomy devices. The use of retrievable stents and suction through a balloon guide catheter during thrombus retrieval was also recommended.
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The primary outcome was the odds ratio that the intervention would lead to lower scores on the mRS at 90 days (shift analysis).

 

Results:
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Interim analysis after the O'Brien Fleming stopping boundary was crossed.
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Primary Outcome: The adjusted odds ratio (indicating the odds of improvement of 1 point on the mRS) was 3.1 (95% CI, 2.0 to 4.7) favoring endovascular intervention.
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The difference in proportion of patients with a mRS of 0-2 at 90 days was 53% in favor of the intervention group versus 23.7% in the control group (p<0.001).
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Retrievable stents were used in 86.1% who underwent an endovascular procedure.
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TICI 2b/3 recanalization was observed in 72.4% in the endovascular group.
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The number randomized after 6 hours was too small to reach any conclusions regarding intervention beyond 6 hours.

 

COMMENT

used cta AND ct-p AND ASPECTS SCORE

MR Clean results

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A PROBE, two-arm, superiority trial that studied 500 patients with acute ischemic stroke caused by an proximal intracranial occlusion in the anterior circulation [distal intracranial carotid artery, middle cerebral artery (M1 or M2), or anterior cerebral artery (A1 or A2)] established by computed tomographic angiography (CTA), magnetic resonance angiography (MRA), or digital-subtraction angiography (DSA), and a score of 2 or higher on the NIHSS
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Initiation of endovascular treatment within 6 hours of stroke onset had to be possible.
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Patients who were eligible in agreement with national guidelines received IV rtPA. Those with a non-favorable response were eligible for inclusion.

 

Results:
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Randomized 1:1 (usual care, IA treatment plus usual care)
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Occlusion site: M1 (64%), ICA + M1 (27%)
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Onset to groin puncture: 260 (210-313 IQR) minutes
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Stent retriever used in: 81.5%
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TICI 2b/3 revascularization in 59%; Stroke to reperfusion time: 322 (279-394 IQR) minutes
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The treatment effect was estimated as an odds ratio, adjusted for pre-specified prognostic factors, that IA treatment would lead to lower mRS at 90 days, as compared with usual care alone (shift analysis)
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Outcome:Absolute difference of 13.5% (95% CI, 1.21 to 2.30) in achieving mRS 0-2 in favor of the intervention group
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This difference became non-significant if reperfusion was delayed > 6.2 hours

 

COMMENT- MAY SUPPORT NOT INTERVENING AFTER SIX HOURS

 

ONSET TO GROIN PUNCTURE 4.3 HOURS

ONSET TO REPERFUSION 5.3 HOURS