Response by Flint et al to Letter Regarding Article, “Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment”

HomeStrokeVol. 52, No. 1Response by Flint et al to Letter Regarding Article, “Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBResponse by Flint et al to Letter Regarding Article, “Risk of Distal Embolization From tPA (Tissue-Type Plasminogen Activator) Administration Prior to Endovascular Stroke Treatment” Alexander C. Flint, MD, PhD, Andy L. Avins, MD and Mai N. Nguyen-Huynh, MD, MAS Alexander C. FlintAlexander C. Flint https://orcid.org/0000-0002-3721-2694 Division of Research, Kaiser Permanente Northern California, Oakland, CA (A.C.F., A.L.A., M.N.N.). Department of Neurology, Kaiser Permanente, Redwood City, CA (A.C.F.). Search for more papers by this author , Andy L. AvinsAndy L. Avins Division of Research, Kaiser Permanente Northern California, Oakland, CA (A.C.F., A.L.A., M.N.N.). Search for more papers by this author and Mai N. Nguyen-HuynhMai N. Nguyen-Huynh Division of Research, Kaiser Permanente Northern California, Oakland, CA (A.C.F., A.L.A., M.N.N.). Department of Neurology, Kaiser Permanente, Walnut Creek, CA (M.N.N.). Search for more papers by this author Originally published28 Dec 2020https://doi.org/10.1161/STROKEAHA.120.032903Stroke. 2021;52:e39–e40In Response:We appreciate the interest in our recent article in Stroke1 and the thoughtful letters written by Katsanos and Tsivgoulis and by Tan and Xu.In contrast to the prior observation referred to in Katsanos and Tsivgoulis’ letter, we do not find that intravenous tPA (tissue-type plasminogen activator) pretreatment is associated with improved rates of recanalization with endovascular stroke treatment (EST). In univariable analysis, the rate of modified Treatment in Cerebral Ischemia (mTICI) 2b/3 target recanalization was 71.8% (168/234) among patients pretreated with tPA and 79.6% (74/93) among patients not treated with tPA. There was similarly no impact of tPA in multivariable logistic regression of TICI 2b/3 recanalization (controlling for age, gender, race/ethnicity, and medical comorbidities); odds ratio for tPA, 0.67 (95% CI, 0.37–1.22; P=0.188).Tan and Xu’s comments largely center on the fact that our study was based in a real-world large cohort of patients treated in primary stroke centers and comprehensive stroke centers in Northern California.1,2 There was no bias related to enrollment, as there was no prospective study enrollment—this was an observational study of a regional clinical practice, and all subjects meeting a priori eligibility criteria, as described, were included in the analysis. We do agree, however, that a central caveat of any observational cohort study is the potential for confounding (in this case, the possibility that other factors related to the tPA treatment decision might be responsible for observed associations between tPA and outcomes such as distal embolization). However, treatment decisions regarding tPA and EST in this cohort were all regionally standardized as part of the Kaiser Permanente Stroke EXPRESS program, as previously described.2 The mean time from computed tomographic angiography to groin puncture at EST reported in our study, as called out by Tan and Xu, reflects the reality of transport in the geographically spread-out yet congested San Francisco Bay Area and its surrounding communities. The concerns that Tan and Xu express regarding our definitions of middle cerebral artery segments and distal embolization are unfounded: as we described in our Methods section, we used standard definitions for middle cerebral artery segments3 and standardized, prespecified, definitions for distal embolization.The stroke community remains in equipoise regarding whether tPA conveys net benefit or net harm (or has no net impact) before EST for large vessel occlusion. Our study serves to highlight one downside of tPA (distal embolization) that was previously under-recognized and which might counterbalance the possibility that tPA could, on its own, lead to complete recanalization of a large vessel occlusion. The question of whether tPA should or should not be given before EST for large vessel occlusion cannot be answered by observational data such as ours: this treatment choice must be settled by randomized controlled trials.Of note, one of the randomized controlled trials organized to address this issue, DIRECT-MT, has been completed, and this trial found that direct EST was noninferior to tPA+EST, with nonsignificant differences in 90-day clinical outcome, the rate of EST recanalization, and the rate of symptomatic intracranial hemorrhage, despite a significantly higher rate of pre-EST recanalization after tPA.4 Further randomized controlled trial results will be needed to decide if the standard approach (intravenous tPA+EST) should remain in place or if it should be changed in favor of direct EST. It is also possible that a one-size-fits-all approach might not suffice: patients presenting directly to EST centers might benefit from one approach, while patients presenting first to a non-EST center (and thus requiring secondary transport to an EST center) might benefit from another.Sources of FundingNone.DisclosuresDr Avins received funding from The Permanente Medical Group. Dr Nguyen-Huynh received grant funding from the National Institutes of Health (NIH)/National Institute for Neurological Disorders and Stroke (NINDS). The other author reports no conflicts.FootnotesThis article was sent to Marc Fisher, Senior Consulting Editor, for editorial decision and final disposition.For Sources of Funding and Disclosures, see page e40.References1. Flint AC, Avins AL, Eaton A, Uong S, Cullen SP, Hsu DP, Edwards NJ, Reddy PA, Klingman JG, Rao VA, et al.. Risk of distal embolization from tPA (Tissue-type plasminogen activator) administration prior to endovascular stroke treatment.Stroke. 2020; 51:2697–2704. doi: 10.1161/STROKEAHA.120.029025LinkGoogle Scholar2. Nguyen-Huynh MN, Klingman JG, Avins AL, Rao VA, Eaton A, Bhopale S, Kim AC, Morehouse JW, Flint AC; KPNC Stroke FORCE Team. Novel telestroke program improves thrombolysis for acute stroke across 21 hospitals of an integrated healthcare system.Stroke. 2018; 49:133–139. doi: 10.1161/STROKEAHA.117.018413LinkGoogle Scholar3. Gibo H, Carver CC, Rhoton AL, Lenkey C, Mitchell RJ. Microsurgical anatomy of the middle cerebral artery.J Neurosurg. 1981; 54:151–169. doi: 10.3171/jns.1981.54.2.0151CrossrefMedlineGoogle Scholar4. Yang P, Zhang Y, Zhang L, Zhang Y, Treurniet KM, Chen W, Peng Y, Han H, Wang J, Wang S, et al.; DIRECT-MT Investigators. Endovascular thrombectomy with or without intravenous alteplase in acute stroke.N Engl J Med. 2020; 382:1981–1993. doi: 10.1056/NEJMoa2001123CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails January 2021Vol 52, Issue 1Article InformationMetrics © 2020 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.120.032903PMID: 33370202 Originally publishedDecember 28, 2020 PDF download Advertisement SubjectsCerebrovascular Disease/Stroke