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Response to Letter Regarding Article, “Clot Length Distribution and Predictors in Anterior Circulation Stroke: Implications for Intra-Arterial Therapy”
We thank Wanklyn et al1 for their comments. We agree wholeheartedly that even in the setting of long clots (eg, ≥8 mm), intravenous recombinant tissue-type plasminogen activator (tPA) should be administered rapidly to eligible acute ischemic stroke patients. Although the probability of early intravenous tPA recanalization of such clots is low, it is not zero, as demonstrated by the cases provided. Indeed, in a nonrandomized Virtual International Stroke Trials Archive (VISTA) study, intravenous tPA benefit extended to patients with severe neurological deficits, up to National Institutes of Health Stroke Scale score of 24.2 We know that many of these patients with severe stroke harbor proximal occlusions and long clots. One argument against intravenous tPA use for long clots is that it may increase the risk of additional intra-arterial therapy (IAT). However, data from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trials demonstrated no difference in hemorrhage or procedural complications from IAT whether intravenous tPA was administered beforehand.3 We also agree that the added benefit of IAT after intravenous tPA is uncertain, and that patients should be enrolled into one of the trials seeking to answer this question. However, absent this option, it remains reasonable to treat intravenous tPA-refractory patients with IAT. First, we know from Interventional Management of Stroke III (IMS III) that the bridging approach is as safe as intravenous tPA alone.4 With respect to 90-day functional independence, it is important to recognize that a trial may fail for reasons besides the treatment under investigation. In IMS III, significant limitations included no requirement for a documented vessel occlusion and the small number of s tent-retrievers used. By comparison, a nonrandomized study of middle cerebral artery occlusions demonstrated significantly improved outcomes with a bridging approach that used stent-retrievers compared with intravenous tPA alone.5 IMS III also showed us that time to intra-arterial revascularization is critical. This is particularly relevant for the question of how long we should wait before we declare intravenous tPA failure and proceed to IAT. Many centers wait ≥30 minutes. This same delay has been associated with a 10% relative reduction in the probability of good outcome in IMS III.6 Rather than incur this delay in all patients, a better approach may be to use clot imaging to identify patients more likely to fail intravenous thrombolysis (ie, middle cerebral artery occlusions with clots ≥8 mm and terminal ICA occlusions) and take them to IAT
immediately. The clinical efficacy of this selection paradigm is being tested in the THERAPY trial. At our institution, we use an alternative approach where we proceed directly to IAT after the intravenous tPA infusion has started, for all patients with a documented occlusion (regardless of clot length) who are deemed to be good candidates. We forego treatment if there is dramatic clinical improvement or if the initial angiogram reveals complete revascularization. In the latter scenario, we think that the potential benefits of rapid treatment outweigh the minimal risks of diagnostic angiography.
Disclosures Dr Yoo has received research support from Penumbra Inc, National Institutes of Health, and Remedy Pharmaceuticals Inc. The other authors report no conflicts.
Shervin Kamalian, MD, MMSc Livia T. Morais, MD Albert J. Yoo, MD Division of Diagnostic and Interventional Neuroradiology Massachusetts General Hospital Boston, MA 1. Wanklyn P, Ramadan H, Patankar T. Letter by Wanklyn et al Regarding Article, “Clot Length Distribution and Predictors in Anterior Circulation Stroke: Implications for Intra-Arterial Therapy”. Stroke. 2014;45:e30. 2. Mishra NK, Lyden P, Grotta JC, Lees KR; VISTA Collaborators. Thrombolysis is associated with consistent functional improvement across baseline stroke severity: a comparison of outcomes in patients from the Virtual International Stroke Trials Archive (VISTA). Stroke. 2010;41:2612–2617. 3. Shi ZS, Loh Y, Walker G, Duckwiler GR; MERCI and Multi MERCI Investigators. Endovascular thrombectomy for acute ischemic stroke in failed intravenous tissue plasminogen activator versus non-intravenous tissue plasminogen activator patients: revascularization and outcomes stratified by the site of arterial occlusions. Stroke. 2010;41:1185–1192. 4. Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, et al; Interventional Management of Stroke (IMS) III Investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013;368:893–903. 5. Vendrell JF, Mernes R, Nagot N, Milhaud D, Lobotesis K, Costalat V, et al. Evaluation of an intravenous-endovascular strategy in patients with acute proximal middle cerebral artery occlusion. Am J Neuroradiol. 2013;34:603–608. 6. Khatri P, IMS III Investigators. Time to angiographic reperfusion is highly associated with good clinical outcome in the ims iii trial. International Stroke Conference. Honolulu, Hawaii, February 6–8, 2013. Abstract LB9.
(Stroke. 2014;45:e31.) © 2014 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.113.004268
Downloaded from http://stroke.ahajournals.org/ by guest on September 14, 2015 e31
Response to Letter Regarding Article, ''Clot Length Distribution and Predictors in Anterior Circulation Stroke: Implications for Intra-Arterial Therapy'' Shervin Kamalian, Livia T. Morais and Albert J. Yoo Stroke. 2014;45:e31; originally published online January 9, 2014; doi: 10.1161/STROKEAHA.113.004268 Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/45/2/e31
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke.ahajournals.org//subscriptions/
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Response to Letter Regarding Article, “Clot Length Distribution and Predictors in Anterior Circulation Stroke: Implications for Intra-Arterial Therapy”
We thank Wanklyn et al1 for their comments. We agree wholeheartedly that even in the setting of long clots (eg, ≥8 mm), intravenous recombinant tissue-type plasminogen activator (tPA) should be administered rapidly to eligible acute ischemic stroke patients. Although the probability of early intravenous tPA recanalization of such clots is low, it is not zero, as demonstrated by the cases provided. Indeed, in a nonrandomized Virtual International Stroke Trials Archive (VISTA) study, intravenous tPA benefit extended to patients with severe neurological deficits, up to National Institutes of Health Stroke Scale score of 24.2 We know that many of these patients with severe stroke harbor proximal occlusions and long clots. One argument against intravenous tPA use for long clots is that it may increase the risk of additional intra-arterial therapy (IAT). However, data from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trials demonstrated no difference in hemorrhage or procedural complications from IAT whether intravenous tPA was administered beforehand.3 We also agree that the added benefit of IAT after intravenous tPA is uncertain, and that patients should be enrolled into one of the trials seeking to answer this question. However, absent this option, it remains reasonable to treat intravenous tPA-refractory patients with IAT. First, we know from Interventional Management of Stroke III (IMS III) that the bridging approach is as safe as intravenous tPA alone.4 With respect to 90-day functional independence, it is important to recognize that a trial may fail for reasons besides the treatment under investigation. In IMS III, significant limitations included no requirement for a documented vessel occlusion and the small number of s tent-retrievers used. By comparison, a nonrandomized study of middle cerebral artery occlusions demonstrated significantly improved outcomes with a bridging approach that used stent-retrievers compared with intravenous tPA alone.5 IMS III also showed us that time to intra-arterial revascularization is critical. This is particularly relevant for the question of how long we should wait before we declare intravenous tPA failure and proceed to IAT. Many centers wait ≥30 minutes. This same delay has been associated with a 10% relative reduction in the probability of good outcome in IMS III.6 Rather than incur this delay in all patients, a better approach may be to use clot imaging to identify patients more likely to fail intravenous thrombolysis (ie, middle cerebral artery occlusions with clots ≥8 mm and terminal ICA occlusions) and take them to IAT
immediately. The clinical efficacy of this selection paradigm is being tested in the THERAPY trial. At our institution, we use an alternative approach where we proceed directly to IAT after the intravenous tPA infusion has started, for all patients with a documented occlusion (regardless of clot length) who are deemed to be good candidates. We forego treatment if there is dramatic clinical improvement or if the initial angiogram reveals complete revascularization. In the latter scenario, we think that the potential benefits of rapid treatment outweigh the minimal risks of diagnostic angiography.
Disclosures Dr Yoo has received research support from Penumbra Inc, National Institutes of Health, and Remedy Pharmaceuticals Inc. The other authors report no conflicts.
Shervin Kamalian, MD, MMSc Livia T. Morais, MD Albert J. Yoo, MD Division of Diagnostic and Interventional Neuroradiology Massachusetts General Hospital Boston, MA 1. Wanklyn P, Ramadan H, Patankar T. Letter by Wanklyn et al Regarding Article, “Clot Length Distribution and Predictors in Anterior Circulation Stroke: Implications for Intra-Arterial Therapy”. Stroke. 2014;45:e30. 2. Mishra NK, Lyden P, Grotta JC, Lees KR; VISTA Collaborators. Thrombolysis is associated with consistent functional improvement across baseline stroke severity: a comparison of outcomes in patients from the Virtual International Stroke Trials Archive (VISTA). Stroke. 2010;41:2612–2617. 3. Shi ZS, Loh Y, Walker G, Duckwiler GR; MERCI and Multi MERCI Investigators. Endovascular thrombectomy for acute ischemic stroke in failed intravenous tissue plasminogen activator versus non-intravenous tissue plasminogen activator patients: revascularization and outcomes stratified by the site of arterial occlusions. Stroke. 2010;41:1185–1192. 4. Broderick JP, Palesch YY, Demchuk AM, Yeatts SD, Khatri P, Hill MD, et al; Interventional Management of Stroke (IMS) III Investigators. Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med. 2013;368:893–903. 5. Vendrell JF, Mernes R, Nagot N, Milhaud D, Lobotesis K, Costalat V, et al. Evaluation of an intravenous-endovascular strategy in patients with acute proximal middle cerebral artery occlusion. Am J Neuroradiol. 2013;34:603–608. 6. Khatri P, IMS III Investigators. Time to angiographic reperfusion is highly associated with good clinical outcome in the ims iii trial. International Stroke Conference. Honolulu, Hawaii, February 6–8, 2013. Abstract LB9.
(Stroke. 2014;45:e31.) © 2014 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.113.004268
Downloaded from http://stroke.ahajournals.org/ by guest on September 14, 2015 e31
Response to Letter Regarding Article, ''Clot Length Distribution and Predictors in Anterior Circulation Stroke: Implications for Intra-Arterial Therapy'' Shervin Kamalian, Livia T. Morais and Albert J. Yoo Stroke. 2014;45:e31; originally published online January 9, 2014; doi: 10.1161/STROKEAHA.113.004268 Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 2014 American Heart Association, Inc. All rights reserved. Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the World Wide Web at: http://stroke.ahajournals.org/content/45/2/e31
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answer document. Reprints: Information about reprints can be found online at: http://www.lww.com/reprints Subscriptions: Information about subscribing to Stroke is online at: http://stroke.ahajournals.org//subscriptions/
Downloaded from http://stroke.ahajournals.org/ by guest on September 14, 2015
