Benchmarking the Extent and Speed of Reperfusion: First Pass TICI 2c-3 Is a Preferred Endovascular Reperfusion Endpoint

THIS is the whole problem in stroke. An endpoint of reperfusion, NOT RECOVERY! Will you talk to survivors sometime? They don't give a shit about reperfusion, it's only an intermediate step to recovery. What are the rest of the protocols to get to 100% recovery?

Benchmarking the Extent and Speed of Reperfusion: First Pass TICI 2c-3 Is a Preferred Endovascular Reperfusion Endpoint

Albert J. Yoo^1*, Jazba Soomro¹, Tommy Andersson^2,3, Jeffrey L. Saver⁴, Marc Ribo⁵, Hormozd Bozorgchami⁶, Guilherme Dabus⁷, David S. Liebeskind⁸, Ashutosh Jadhav⁹, Heinrich Mattle¹⁰ and Osama O. Zaidat¹¹ on behalf of ARISE II Investigators

• ¹Department of Neurointervention, Texas Stroke Institute, Fort Worth, TX, United States
• ²Neuroradiology, Karolinska University Hospital, Clinical Neuroscience Karolinska Institutet, Stockholm, Sweden
• ³Medical Imaging, Allgemeine Ziekenhuis Groeninge, Kortrijk, Belgium
• ⁴Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States
• ⁵Stroke Unit, Department of Neurology, Vall D'Hebron University Hospital, Barcelona, Spain
• ⁶Department of Neurology, Oregon Health and Science University Hospital, Portland, OR, United States
• ⁷Department of Interventional Neuroradiology, Miami Cardiac and Vascular Institute at Baptist Hospital of Miami, Miami, FL, United States
• ⁸Department of Neurology, Neurovascular Imaging Research Core and Stroke Center, University of California, Los Angeles, Los Angeles, CA, United States
• ⁹Department of Neurology, University of Pittsburgh Medical Center, Pittsburgh, PA, United States
• ¹⁰Department of Neurology, Inselspital, University of Bern, Bern, Switzerland
• ¹¹Mercy St. Vincent Medical Center, Toledo, OH, United States

Background and Purpose: End-of-procedure substantial reperfusion [modified Treatment in Cerebral Ischemia (mTICI) 2b-3], the leading endpoint for thrombectomy studies, has several limitations including a ceiling effect, with recent achieved rates of ~90%. We aimed to identify a more optimal definition of angiographic success along two dimensions: (1) the extent of tissue reperfusion, and (2) the speed of revascularization.

Methods: Core-lab adjudicated TICI scores for the first three passes of EmboTrap and the final all-procedures result were analyzed in the ARISE II multicenter study. The clinical impact of extent of reperfusion and speed of reperfusion (first-pass vs. later-pass) were evaluated. Clinical outcomes included 90-day functional independence [modified Rankin Scale (mRS) 0–2], 90-day freedom-from-disability (mRS 0–1), and dramatic early improvement [24-h National Institutes of Health Stroke Scale (NIHSS) improvement ≥ 8 points].

Results: Among 161 ARISE II subjects with ICA or MCA M1 occlusions, reperfusion results at procedure end showed substantial reperfusion in 149 (92.5%), excellent reperfusion in 121 (75.2%), and complete reperfusion in 79 (49.1%). Reperfusion rates on first pass were substantial in 81 (50.3%), excellent reperfusion in 62 (38.5%), and complete reperfusion in 44 (27.3%). First-pass excellent reperfusion (first-pass TICI 2c-3) had the greatest nominal predictive value for 90-day mRS 0–2 (sensitivity 58.5%, specificity 68.6%). There was a progressive worsening of outcomes with each additional pass required to achieve TICI 2c-3.

Conclusions: First-pass excellent reperfusion (TICI 2c-3), reflecting rapid achievement of extensive reperfusion, is the technical revascularization endpoint that best predicted functional independence in this international multicenter trial and is an attractive candidate for a lead angiographic endpoint for future trials.

Clinical Trial Registration: http://www.clinicaltrials.gov, identifier NCT02488915.

Introduction

The current consensus statement-endorsed benchmark for procedural success after intra-arterial stroke therapy (IAT) is procedure end substantial reperfusion [modified Treatment in Cerebral Ischemia (mTICI) score of 2b or higher], defined as the restoration of anterograde tissue perfusion in more than 50% of the target downstream territory (1, 2). The impressive clinical benefits observed in recent thrombectomy trials reflected improved reperfusion with second generation devices, most notably stent retrievers (3, 4). Since these pivotal trials, there has been a further increase in reported rates of substantial reperfusion (5). In the recent ARISE (Analysis of Revascularization in Ischemic Stroke with EmboTrap) II study, the core lab-adjudicated TICI 2b-3 rate at procedure end was 92.5% (6).

However, there are considerable limitations to using the rate of TICI 2b-3 as a lead technical efficacy endpoint for IAT trials. First, this endpoint counts moderate reperfusion as a success, but when reperfusion is only 50–90% achieved, substantial tissue volumes remain in jeopardy. Second, the outcome of TICI 2b-3 is considered a success regardless of the number of passes required to achieve it, but maximal benefit is likely to be conferred by first-pass success, thus reducing ischemia duration (7). Third, the high rate of TICI 2b-3 seen with modern endovascular technology results in a ceiling effect, making the measure insensitive to further improvements in endovascular technique. Accordingly, a reevaluation of the optimal angiographic endpoint is necessary.

Using core-lab adjudicated data from ARISE II, we aimed to assess the clinical impact of the first-pass effect (FPE) and to identify the optimal definition of angiographic success along two dimensions: (1) the extent of tissue reperfusion, and (2) the speed of revascularization.

More at link.