Thrombectomy in Acute Stroke Christopher J. White, MD, MSCAI Prof and Chairman of Medicine Ochsner Medical Center

Disclosures: Stroke Intervention Christopher J. White MD Research: None. Speakers: Nada. Stock: Zero. Consultant: Nothing.

Ischemic Stroke Therapy PATIENT SELECTION IV Thrombolysis ≤ 4.5 hrs from onset. Widely available. Restricted population. No bleed on CT. SBP < 185 mmHg DBP < 110 mmHg Low bleeding risk. Mechanical Thrombectomy ≤ 6 hrs from onset. ASPECTS > 6. Large vessel occlusion. Disabling strokes (NIHSS > 5). MCA occlusion. Speech impaired. Vision impaired.

NINDS Trial 10x 624 pts randomized within 3 hrs. National Institute of Neurological Disorders and Stroke rt-PA Study Group M2 BASELINE 624 pts randomized within 3 hrs. Placebo Rt-PA 0.9 mg/kg (max 90 mg) over 1 hr. Neurological assessment TPA increased full recovery rate 21% to 34% (32% relative) at 3 months (OR=1.7 (95%CI 1.2- 2.6) p= 0.008). Mortality not different between groups. IC bleed rt-PA 6.4% vs 0.6% (p < 0.001). IV-tPA 10x NEJM 1995;333:1581-7.

EARLY TRIALS: Mechanical Thrombectomy The initial trials did not demonstrate conclusive benefit for endovascular therapy, although there were promising signals. There seemed to be a balance between early and effective mechanical reperfusion with the risk of intracranial hemorrhage (ICH) that was related to reperfusion of nonviable brain. MERCI MR RESCUE SYNTHESIS EXP IMS-III

Interventional Management of Stroke IMS-III: Early Trials Interventional Management of Stroke No benefit for MT ± IV-TPA vs. IV-TPA in moderate to severe acute ischemic stroke. However, there were significant weaknesses. CTA was not required, which allowed the inclusion of patients who did not have intracranial large-vessel occlusion. First generation MT devices used. Merci Retriever

PARADIGM SHIFT MR CLEAN ESCAPE EXTEND IA SWIFT PRIME REVASCAT Between December 2014 and April 2015, 5 RCTS provided compelling evidence that mechanical thrombectomy (MT) improves outcomes after acute ischemic stroke. MT significantly improved clinical outcome in patients with proximal intracranial occlusion of the anterior circulation compared with IV t-PA. MR CLEAN ESCAPE EXTEND IA SWIFT PRIME REVASCAT

EVOLUTION OF STROKE Rx The major differences between these positive endovascular trials and past trials were: CTA to select patients with LVO. Select viable brain (penumbra). Stent retrievers for thrombectomy. Papanagiotou P. and White C. J Am Coll Cardiol Intv. 2016; 9(4):307–17.

Strategy: Early Treatment Time to Rx Reperfusion Flow (A) Relationship between onset to intra-arterial therapy/reperfusion and NNT in patients undergoing EVT among second- and third-generation endovascular trials. The NNT to have good outcome decreases with rapid treatment times. (B) Relationship between good reperfusion (TICI 2b) score and NNT among second- and third-generation trials. IA = intra-arterial; IMS = Interventional Management of Stroke; MR CLEAN = Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; MR RESCUE = Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy; NNT = number needed to treat; TICI = Thrombolysis In Cerebral Infarction; other abbreviations as in Figure 4. Khandelwal P, et al. J Am Coll Cardiol 2016;67:2631–44.

Strategy: Effective Reperfusion Good Reperfusion Good Neurologic Outcomes NNT (A) Relationship between onset to intra-arterial therapy/reperfusion and NNT in patients undergoing EVT among second- and third-generation endovascular trials. The NNT to have good outcome decreases with rapid treatment times. (B) Relationship between good reperfusion (TICI 2b) score and NNT among second- and third-generation trials. IA = intra-arterial; IMS = Interventional Management of Stroke; MR CLEAN = Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands; MR RESCUE = Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy; NNT = number needed to treat; TICI = Thrombolysis In Cerebral Infarction; other abbreviations as in Figure 4. Khandelwal P, et al. J Am Coll Cardiol 2016;67:2631–44.

META-ANALYSIS Pooled estimates for achieving modified Rankin Scale (mRS) 0-2 outcomes with Endovascular Recanalization Therapy vs. Control. Pooling all RCT’s (SWIFT PRIME [Solitaire with the Intention for Thrombectomy as Primary Endovascular Treatment], ESCAPE [Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times], EXTEND-IA [Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial], REVASCAT [Randomized Trial of Revascularization with Solitaire FR Device versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation LVO Presenting within Eight Hours of Symptom Onset]), adjusted for age, sex, baseline stroke severity, site of occlusion, intravenous alteplase treatment, carotid occlusion, Alberta Stroke Program CT Score, and time from onset to treatment to randomization. Reprinted with permission from Campbell et al. (31). ASPECTS = Alberta Stroke Program Early CT Score; CI = confidence interval; ICA = internal carotid artery; MCA = middle cerebral artery; NIHSS = National Institute of Health Stroke Scale. Hong KS, et al. J Stroke. 2015 Sep; 17(3): 268–281

OPTIMAL MANAGEMENT OF ACUTE ISCHEMIC STROKE SUMMARY OPTIMAL MANAGEMENT OF ACUTE ISCHEMIC STROKE Onset to Rx ≤ 6hrs Shorter times to reperfusion. Improved patient selection. Better thrombectomy devices. Aspects ≥ 6 NIHSS ≥ 5 Large Vessel Occlusion Stent Retrievers Khandelwal P, et al. J Am Coll Cardiol 2016;67:2631–44.